The Open Biochemistry Journal[JOURNAL]
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130 papers
In the Huh7 Hepatoma Cells Diclofenac and Indomethacin Activate Differently the Unfolded Protein Response and Induce ER Stress Apoptosis.
Franceschelli S, Moltedo O, Amodio G … +2 more , Tajana G, Remondelli P
Open Biochem J · 2011 · PMID 21966325 · Full text
Non-steroidal anti-inflammatory drugs (NSAIDs) are cyclooxygenases (COXs) inhibitors frequently used in the treatment of acute and chronic inflammation. Side effects of NSAIDs are often due to their ability to induce apo...
Non-steroidal anti-inflammatory drugs (NSAIDs) are cyclooxygenases (COXs) inhibitors frequently used in the treatment of acute and chronic inflammation. Side effects of NSAIDs are often due to their ability to induce apoptosis. Located at the Endoplasmic Reticulum membranes a tripartite signalling pathway, collectively known as the Unfolded Protein Response (UPR), decides survival or death of cells exposed to cytotoxic agents. To shed light on the molecular events responsible for the cytotoxicity of NSAIDs, we analysed the ability of diclofenac and indomethacin to activate the UPR in the human hepatoma cell line Huh7. We report that both NSAIDs can induce differently the single arms of the UPR. We show that indomethacin turns on the PERK and, only in part, the ATF6 and IRE1 pathways. Instead, diclofenac reduces the expression of ATF6 and does not stimulate the IRE1 endonuclease, which drives the expression of the prosurvival factor XBP1. Diclofenac, as well as indomethacin, is able to activate efficiently only the PERK pathway of the UPR, which induces the expression of the proapoptotic GADD153/CHOP protein. Our results highlight the importance of the UPR in evaluating the potential of drugs to induce apoptosis.
Thalidomide Analogues Suppress Lipopolysaccharide-Induced Synthesis of TNF-α and Nitrite, an Intermediate of Nitric Oxide, in a Cellular Model of Inflammation.
Tweedie D, Frankola KA, Luo W … +2 more , Li Y, Greig NH
Open Biochem J · 2011 · PMID 21792375 · Full text
An unregulated neuroinflammation accompanies numerous chronic and acute neurodegenerative disorders and it is postulated that such a neuroinflammatory component likely exacerbates disease progression. A key player in bra...
An unregulated neuroinflammation accompanies numerous chronic and acute neurodegenerative disorders and it is postulated that such a neuroinflammatory component likely exacerbates disease progression. A key player in brain inflammation is the microglial cell; a vital soluble factor synthesized by activated microglial cells is the key cytokine, tumor necrosis factor-alpha (TNF-α). Additionally, microglial cells release IL-1α/β, reactive oxygen species (ROS), such as superoxide (O(2) (-)) and reactive nitrogen species (RNS) like nitric oxide (NO). Nitric oxide reactive oxygen species can undergo various forms of interactions in cells whereby the synthesis of RNS / ROS intermediates are generated that can damage cell membranes. The presence of oxidative damaged cells is implicated with the abnormal cellular activity in brain or in the spinal cord, and is a classical feature of neurodegenerative disorders. To aid characterize this process, a quantitative analysis of nitrite generation was undertaken on agents developed to lower TNF-α levels in cell culture. Nitrite is a stable end product of nitric oxide metabolism and, thereby, acts as a surrogate measure of the highly unstable nitric oxide. Utilizing a RAW 264.7 cellular model of lipopolysaccharide-induced inflammation that induces high levels of TNF-α protein accompanied by a robust generation of nitrite, the properties of a series of thalidomide-based TNF-α synthesis inhibitors were evaluated to reduce the levels of both. Specific analogues of thalidomide effectively suppressed the generation of both TNF-α and nitrite at well-tolerated doses.
Regions which are Responsible for Swapping are also Responsible for Folding and Misfolding.
Galzitskaya OV
Open Biochem J · 2011 · PMID 21769300 · Full text
Domain swapping is a term used to describe a process when two or more protein chains exchange identical structural elements. Some cases of amyloid formation can be explained through a domain swapping mechanism therefore...
Domain swapping is a term used to describe a process when two or more protein chains exchange identical structural elements. Some cases of amyloid formation can be explained through a domain swapping mechanism therefore this deserves theoretical consideration and studying. It has been demonstrated that diverse proteins in sequence and structure are able to oligomerize via domain swapping. This allows us to suggest that the exchangeable regions are important in folding and misfolding processes of proteins, i.e. the residues from the swapping regions are typically incorporated into the native structure early during its formation. The modeling of folding of the proteins with swapped domains demonstrates that the regions exchanged in the oligomeric form in most cases are also responsible for folding and misfolding. For 11 out of 17 proteins, swapping regions intersect with the predicted amyloidogenic regions. Moreover, for 10 out of 17 proteins, high Φ-values (>0.5) belong to residues from the swapping regions. Our data confirm that the exchangeable regions are important in folding, misfolding, and domain swapping processes of the proteins, therefore the suggestion that domain swapping can serve as a mechanism for functional interconversion between monomers and oligomers is likely to be correct.
Parkin, A Top Level Manager in the Cell's Sanitation Department.
Rankin CA, Roy A, Zhang Y … +1 more , Richter M
Open Biochem J · 2011 · PMID 21633666 · Full text
Parkin belongs to a class of multiple RING domain proteins designated as RBR (RING, in between RING, RING) proteins. In this review we examine what is known regarding the structure/function relationship of the Parkin pro...
Parkin belongs to a class of multiple RING domain proteins designated as RBR (RING, in between RING, RING) proteins. In this review we examine what is known regarding the structure/function relationship of the Parkin protein. Parkin contains three RING domains plus a ubiquitin-like domain and an in-between-RING (IBR) domain. RING domains are rich in cysteine amino acids that act as ligands to bind zinc ions. RING domains may interact with DNA or with other proteins and perform a wide range of functions. Some function as E3 ubiquitin ligases, participating in attachment of ubiquitin chains to signal proteasome degradation; however, ubiquitin may be attached for purposes other than proteasome degradation. It was determined that the C-terminal most RING, RING2, is essential for Parkin to function as an E3 ubiquitin ligase and a number of substrates have been identified. However, Parkin also participates in a number of other fiunctions, such as DNA repair, microtubule stabilization, and formation of aggresomes. Some functions, such as participation in a multi-protein complex implicated in NMDA activity at the post synaptic density, do not require ubiquitination of substrate molecules. Recent observations of RING proteins suggest their function may be regulated by zinc ion binding. We have modeled the three RING domains of Parkin and have identified a new set of RING2 ligands. This set allows for binding of two rather than just one zinc ion, opening the possibility that the number of zinc ions bound acts as a molecular switch to modulate Parkin function.
The Oxidative State of LDL is the Major Determinant of Anti/Prooxidant Effect of Coffee on Cu Catalysed Peroxidation.
Carru C, Pasciu V, Sotgia S … +7 more , Zinellu A, Nicoli MC, Deiana L, Tadolini B, Sanna B, Masala B, Pintus G
Open Biochem J · 2011 · PMID 21633665 · Full text
Antioxidants exert contrasting effect on low density lipoprotein (LDL) oxidation catalysed by metals, acting as pro-oxidants under select in vitro conditions. Through our study on the effect of coffee on LDL oxidation, w...
Antioxidants exert contrasting effect on low density lipoprotein (LDL) oxidation catalysed by metals, acting as pro-oxidants under select in vitro conditions. Through our study on the effect of coffee on LDL oxidation, we identified the parameters governing this phenomenon, contributing to the comprehension of its mechanism and discovering significant implications for correct alimentary recommendations. By measuring conjugated diene formation, we have analysed the quantitative and qualitative effects exerted by an extract of roasted coffee on LDL oxidation triggered by copper sulphate. When the relative effects of different coffee concentrations were plotted against the lag time (LT) of control LDL (C-LDL), the apparently random experimental data arranged in sensible patterns: by increasing the LT the antioxidant activity of coffee decreased progressively to become prooxidant. The critical LT, at which coffee switches from antioxidant to prooxidant, increased by increasing coffee concentration. Also the contrasting results obtained following a delayed addition of coffee to the assay, arranged in a simple pattern when referred to the LT of C-LDL: the prooxidant effect decreased to become antioxidant as the LT of C-LDL increased. The dependence of coffee effect on the LT of C-LDL was influenced by LDL but not by metal catalyst concentration. These novel findings point to the oxidative state of LDL as a major parameter controlling the anti/prooxidant effect of coffee and suggest the LT of C-LDL as a potent analytical tool to express experimental data when studying the action exerted by a compound on LDL oxidation.
Systematic comparison of crystal and NMR protein structures deposited in the protein data bank.
Sikic K, Tomic S, Carugo O
Open Biochem J · 2010 Sep · PMID 21293729 · Full text
Nearly all the macromolecular three-dimensional structures deposited in Protein Data Bank were determined by either crystallographic (X-ray) or Nuclear Magnetic Resonance (NMR) spectroscopic methods. This paper reports a...
Nearly all the macromolecular three-dimensional structures deposited in Protein Data Bank were determined by either crystallographic (X-ray) or Nuclear Magnetic Resonance (NMR) spectroscopic methods. This paper reports a systematic comparison of the crystallographic and NMR results deposited in the files of the Protein Data Bank, in order to find out to which extent these information can be aggregated in bioinformatics. A non-redundant data set containing 109 NMR - X-ray structure pairs of nearly identical proteins was derived from the Protein Data Bank. A series of comparisons were performed by focusing the attention towards both global features and local details. It was observed that: (1) the RMDS values between NMR and crystal structures range from about 1.5 Å to about 2.5 Å; (2) the correlation between conformational deviations and residue type reveals that hydrophobic amino acids are more similar in crystal and NMR structures than hydrophilic amino acids; (3) the correlation between solvent accessibility of the residues and their conformational variability in solid state and in solution is relatively modest (correlation coefficient = 0.462); (4) beta strands on average match better between NMR and crystal structures than helices and loops; (5) conformational differences between loops are independent of crystal packing interactions in the solid state; (6) very seldom, side chains buried in the protein interior are observed to adopt different orientations in the solid state and in solution.
Potential therapeutic effects of vitamin e and C on placental oxidative stress induced by nicotine: an in vitro evidence.
Gallo C, Renzi P, Loizzo S … +6 more , Loizzo A, Piacente S, Festa M, Caputo M, Tecce MF, Capasso A
Open Biochem J · 2010 Jun · PMID 20676222 · Full text
There have been a few studies that examined the oxidative stress effects of nicotine during pregnancy and lactation. The adverse effect of prenatal smoking exposure on human fetal development and growth has been a major...
There have been a few studies that examined the oxidative stress effects of nicotine during pregnancy and lactation. The adverse effect of prenatal smoking exposure on human fetal development and growth has been a major public health issue. Active or passive smoking during pregnancy can result in a wide variety of adverse outcomes, including intrauterine growth retardation (IUGR), prematurity, stillbirth, and the sudden infant death syndrome. Smoking in pregnancy has also been associated with an increased risk of attention deficit and learning problems in childhood. Some studies argued that as a principal component of tobacco smoke, nicotine alone is responsible for the majority of negative reproductive outcomes. Nicotine and its major metabolite cotinine can cross the placental barrier. The level of nicotine in fetal tissues was found to be equal to or greater than the plasma nicotine level in the mothers. The oxidative stress induce by nicotine has been increasingly postulated as a major contributor to endothelial dysfunction. A large body of research has investigated the potential role of antioxidant nutrients in the prevention of endothelial dysfunction in women. Therefore, the present study was undertaken to assess the potential benefit of antioxidant supplementation on markers of placental oxidative stress in an in vitro model of endothelial dysfunction induced by nicotine, since it was previously found that nicotine is able to trigger the placental secretion of stress molecules. In this regard, we evaluated the effects of vitamin C, vitamin E and N-acetylcysteine (NAC), alone or in combination, in placental villi culture after exposure to nicotine. The effect of antioxidant nutrients on trophoblast cells proliferation and vitality was also evaluated. The results obtained suggest that in a patho-physiological condition, such as endothelial dysfunction induced by nicotine, the deleterious effect of reactive oxygen species may be counteracted by an antioxidant therapy, and there is the need to investigate the optimum dosing and timing of antioxidants administration, since an inappropriate antioxidant treatment in pregnant women may have deleterious consequences, reducing placental cells proliferation until to cell death.
Leukocyte Count versus C-Reactive Protein Levels in Obese Portuguese Patients Aged 6-12 Years Old.
Nascimento H, Rocha S, Rego C … +4 more , Mansilha HF, Quintanilha A, Santos-Silva A, Belo L
Open Biochem J · 2010 Jun · PMID 20676221 · Full text
OBJECTIVES: to evaluate whether total and differential WBC counts are altered in young obese patients (aged 6-12 years) and if a relationship exists between WBC counts and the severity of obesity as well as with CRP leve...
OBJECTIVES: to evaluate whether total and differential WBC counts are altered in young obese patients (aged 6-12 years) and if a relationship exists between WBC counts and the severity of obesity as well as with CRP level. MATERIALS AND METHODS: a group of 77 obese patients [32 males and 45 females] and 19 controls [7 males and 12 females] were studied. Total WBC count was performed by using an automatic blood cell counter. Blood cell morphology and WBC differential count were evaluated in Wright stained blood films. The plasma levels of CRP were evaluated by immunoturbidimetry. RESULTS: obese participants presented with a statistically significant higher neutrophil percentage and CRP levels when compared to controls; the median CRP value was about 5 times higher than that observed in controls. Absolute neutrophil count and neutrophil/lymphocyte ratio were also higher in patients, though without statistical significance. The parameters that were statistically significant related with adiposity markers were neutrophil count and CRP levels. The neutrophil count was positively and statistically correlated with body mass index (BMI), BMI z-score, waist circumference and waist/height ratio, and also with CRP levels. In multiple regression analysis, the only variable that remained statistically associated with neutrophil count was CRP (neutrophil count = 2.612 + 0.439lnCRP; standardised coefficient/beta: 0.384, P=0.001). When performing multiple regression without CRP, the only variable that remained statistically associated with neutrophil count was BMI. CONCLUSIONS: our results demonstrated in obese patients aged 6-12 years, a significant change in the differential leukocyte count towards neutrophilia, together with a significant higher CRP concentration, and that absolute neutrophil count correlates with obesity markers and with CRP levels. Our data also indicate that neutrophil count, a current clinically used low-cost parameter, may be used as an obesity-related inflammatory marker in young obese patients.
Predominantly Cytoplasmic Localization in Yeast of ASR1, a Non-Receptor Transcription Factor from Plants.
Urtasun N, Correa García S, Iusem ND … +1 more , Bermúdez Moretti M
Open Biochem J · 2010 May · PMID 20657719 · Full text
The Asr gene family (named after abscisic acid, stress and ripening), currently classified as a novel group of the LEA superfamily, is exclusively present in the genomes of seed plants, except for the Brassicaceae family...
The Asr gene family (named after abscisic acid, stress and ripening), currently classified as a novel group of the LEA superfamily, is exclusively present in the genomes of seed plants, except for the Brassicaceae family. It is associated with water-deficit stress and is involved in adaptation to dry climates. Motivated by separate reports depicting ASR proteins as either transcription factors or chaperones, we decided to determine the intracellular localization of ASR proteins. For that purpose, we employed an in vivo eukaryotic expression system, the heterologous model Saccharomyces cerevisiae, including wild type strains as well as mutants in which the variant ASR1 previously proved to be functionally protective against osmotic stress. Our methodology involved immunofluorescence-based confocal microscopy, without artificially altering the native structure of the protein under study. Results show that, in both normal and osmotic stress conditions, recombinant ASR1 turned out to localize mainly to the cytoplasm, irrespective of the genotype used, revealing a scattered distribution in the form of dots or granules. The results are discussed in terms of a plausible dual (cytoplasmic and nuclear) role of ASR proteins.
Conformational States and kinetics of the calcium binding domain of NADPH oxidase 5.
Wei CC, Motl N, Levek K … +5 more , Chen LQ, Yang YP, Johnson T, Hamilton L, Stuehr DJ
Open Biochem J · 2010 May · PMID 20648216 · Full text
Superoxide generated by human NADPH oxidase 5 (NOX5) is of growing importance for various physiological and pathological processes. The activity of NOX5 appears to be regulated by a self-contained Ca(2+) binding domain (...
Superoxide generated by human NADPH oxidase 5 (NOX5) is of growing importance for various physiological and pathological processes. The activity of NOX5 appears to be regulated by a self-contained Ca(2+) binding domain (CaBD). Recently Bánfi et al. suggest that the conformational change of CaBD upon Ca(2+) binding is essential for domain-domain interaction and superoxide production. The authors studied its structural change using intrinsic Trp fluorescence and hydrophobic dye binding; however, their conformational study was not thorough and the kinetics of metal binding was not demonstrated. Here we generated the recombinant CaBD and an E99Q/E143Q mutant to characterize them using fluorescence spectroscopy. Ca(2+) binding to CaBD induces a conformational change that exposes hydrophobic patches and increases the quenching accessibilities of its Trp residues and AEDANS at Cys107. The circular dichroism spectra indicated no significant changes in the secondary structures of CaBD upon metal binding. Stopped-flow spectrometry revealed a fast Ca(2+) dissociation from the N-terminal half, followed by a slow Ca(2+) dissociation from the C-terminal half. Combined with a chemical stability study, we concluded that the C-terminal half of CaBD has a higher Ca(2+) binding affinity, a higher chemical stability, and a slow Ca(2+) dissociation. The Mg(2+)-bound CaBD was also investigated and the results indicate that its structure is similar to the apo form. The rate of Mg(2+) dissociation was close to that of Ca(2+) dissociation. Our data suggest that the N- and C-terminal halves of CaBD are not completely structurally independent.
The impact of the level of the intestinal short chain Fatty acids in inflammatory bowel disease patients versus healthy subjects.
Huda-Faujan N, Abdulamir AS, Fatimah AB … +4 more , Anas OM, Shuhaimi M, Yazid AM, Loong YY
Open Biochem J · 2010 May · PMID 20563285 · Full text
The aim of this study was to determine the changes of short chain fatty acids (SCFAs) in faeces of inflammatory bowel disease (IBD) patients compared to healthy subjects. SCFAs such as pyruvic, lactic, formic, acetic, pr...
The aim of this study was to determine the changes of short chain fatty acids (SCFAs) in faeces of inflammatory bowel disease (IBD) patients compared to healthy subjects. SCFAs such as pyruvic, lactic, formic, acetic, propionic, isobutyric and butyric acids were analyzed by using high performance liquid chromatography (HPLC). This study showed that the level of acetic, 162.0 micromol/g wet faeces, butyric, 86.9 micromol/g wet faeces, and propionic acids, 65.6 micromol/g wet faeces, decreased remarkably in IBD faecal samples when compared with that of healthy individuals, 209.7, 176.0, and 93.3 micromol/g wet faeces respectively. On the contrary, lactic and pyruvic acids showed higher levels in faecal samples of IBD than in healthy subjects. In the context of butyric acid level, this study also found that the molar ratio of butyric acid was higher than propionic acid in both faecal samples. This might be due to the high intake of starch from rice among Malaysian population. It was concluded that the level of SCFAs differ remarkably between faecal samples in healthy subjects and that in IBD patients providing evidence that SCFAs more likely play an important role in the pathogenesis of IBD.
Cardiovascular dementia - a different perspective.
Kumari U, Heese K
Open Biochem J · 2010 Mar · PMID 20448820 · Full text
The number of dementia patients has been growing in recent years and dementia represents a significant threat to aging people all over the world. Recent research has shown that the number of people affected by Alzheimer'...
The number of dementia patients has been growing in recent years and dementia represents a significant threat to aging people all over the world. Recent research has shown that the number of people affected by Alzheimer's disease (AD) and dementia is growing at an epidemic pace. The rapidly increasing financial and personal costs will affect the world's economies, health care systems, and many families. Researchers are now exploring a possible connection among AD, vascular dementia (VD), diabetes mellitus (type 2, T2DM) and cardiovascular diseases (CD). This correlation may be due to a strong association of cardiovascular risk factors with AD and VD, suggesting that these diseases share some biologic pathways. Since heart failure is associated with an increased risk of AD and VD, keeping the heart healthy may prove to keep the brain healthy as well. The risk for dementia is especially high when diabetes mellitus is comorbid with severe systolic hypertension or heart disease. In addition, the degree of coronary artery disease (CAD) is independently associated with cardinal neuropathological lesions of AD. Thus, the contribution of T2DM and CD to AD and VD implies that cardiovascular therapies may prove useful in preventing AD and dementia.
Effects of Detergents on Activity, Thermostability and Aggregation of Two Alkalithermophilic Lipases from Thermosyntropha lipolytica.
Salameh MA, Wiegel J
Open Biochem J · 2010 Mar · PMID 20361033 · Full text
Thermosyntropha lipolytica DSM 11003, an anaerobic thermophilic lipolytic bacterium, produces the two alkalithermophilic lipases, LipA and LipB. Among all tested detergents, the two lipases were mostly affected by SDS wh...
Thermosyntropha lipolytica DSM 11003, an anaerobic thermophilic lipolytic bacterium, produces the two alkalithermophilic lipases, LipA and LipB. Among all tested detergents, the two lipases were mostly affected by SDS when used at concentrations below its critical micelle concentration (CMC). In the absence of SDS, the v(max) of both LipA and LipB were 12.6 U.mg(-1) and 13.3 U.mg(-1) and K(0.5) were 1.8 mM and 1.65 mM, respectively at 96 degrees C and pH(opt) (25 masculineC)of 9.4-9.6. In the presence of 0.2% SDS, the v(max) increased to 105 U.mg(-1) and 112 U.mg(-1), and K(0.5) values decreased to 200 microM and 140 microM for LipA and LipB, respectively. Inhibitory assays of lipases using diisopropyl p-nitrophenylphosphate (E600) with increasing concentration of SDS and Tween 20 strongly suggest that SDS and Tween 20 do bind to the lid domain and/or active site pocket, thus promoting conformational changes that facilitate active site accessibility for the substrate. The two lipases exhibited moderate activation in the presence of nonionic detergents when used below their CMC values. Both lipases were found to exhibit strong tendency to aggregate as observed through gel filtration chromatography and gradient native gel electrophoresis. The addition of 1.0% (w/v) SDS led to disaggregation as the lipases were eluted corresponding to their monomeric mass (based on SDS gel electrophoresis value) and caused a significant decrease in thermostability, suggesting that, enzyme aggregation might be a major contributor to the high thermostability of LipA and LipB.
Investigation of interaction of vaccinia virus complement control protein and curcumin with complement components c3 and c3b using quartz crystal microbalance with dissipation monitoring technology.
Kulkarni AP, Randall PJ, Murthy K … +2 more , Kellaway LA, Kotwal GJ
Open Biochem J · 2010 Jan · PMID 20224684 · Full text
C3 and C3b, the components central to the complement activation, also play a damaging role in several inflammatory disorders. Vaccinia virus complement control protein (VCP) and curcumin (Cur) are natural compounds with...
C3 and C3b, the components central to the complement activation, also play a damaging role in several inflammatory disorders. Vaccinia virus complement control protein (VCP) and curcumin (Cur) are natural compounds with different biological origins reported to regulate complement activation. However, both VCP and Cur have not been investigated for their interaction with the third component (C3) prior to it being converted to its activated form (C3b). These two compounds have also not been compared to each other with respect to their interactions with C3 and C3b. Quartz crystal microbalance with dissipation monitoring (QCM-D) is a novel technology used to study the interaction of biomolecules. This technology was applied to characterize the interactions of VCP, Cur and appropriate controls with the key complement components. Cur as well as VCP showed binding to both C3 and to C3b, Cur however bound to C3b to a lesser extent.
Armadillo Repeat Containing 8alpha Binds to HRS and Promotes HRS Interaction with Ubiquitinated Proteins.
Tomaru K, Ueda A, Suzuki T … +6 more , Kobayashi N, Yang J, Yamamoto M, Takeno M, Kaneko T, Ishigatsubo Y
Open Biochem J · 2010 Jan · PMID 20224683 · Full text
Recently, we reported that a complex with an essential role in the degradation of Fructose-1,6-bisphosphatase in yeast is well conserved in mammalian cells; we named this mammalian complex C-terminal to the Lissencephaly...
Recently, we reported that a complex with an essential role in the degradation of Fructose-1,6-bisphosphatase in yeast is well conserved in mammalian cells; we named this mammalian complex C-terminal to the Lissencephaly type-1-like homology (CTLH) complex. Although the function of the CTLH complex remains unclear, here we used yeast two-hybrid screening to isolate Hepatocyte growth factor-regulated tyrosine kinase substrate (HRS) as a protein binding to a key component of CTLH complex, Armadillo repeat containing 8 (ARMc8) alpha. The association was confirmed by a yeast two-hybrid assay and a co-immunoprecipitation assay. The proline-rich domain of HRS was essential for the association. As demonstrated through immunofluorescence microscopy, ARMc8alpha co-localized with HRS. ARMc8alpha promoted the interaction of HRS with various ubiquitinated proteins through the ubiquitin-interacting motif. These findings suggest that HRS mediates protein endosomal trafficking partly through its interaction with ARMc8alpha.
Molecules Acting on CB1 Receptor and their Effects on Morphine Withdrawal In Vitro.
Capasso A, Gallo C
Open Biochem J · 2009 Dec · PMID 20111725 · Full text
Several pharmacological studies indicate that CB1 cannabinoid receptors (CB1Rs) are present in guinea pig ileum (GPI) and their activation reduce the acetylcholine (Ach) release. Dependence can be induced and measured in...
Several pharmacological studies indicate that CB1 cannabinoid receptors (CB1Rs) are present in guinea pig ileum (GPI) and their activation reduce the acetylcholine (Ach) release. Dependence can be induced and measured in vitro by using GPI and the contraction due to opioid withdrawal is caused by acetylcholine release.Design of molecules acting on the CB1Rs are widely studied and the large availaibility of CB1Rs agonists and antagonists provides powerful tools to determine the role of these receptors in mediating some of physiological and pharmacological effects in the myenteric neurones.Given the relationship between CB1Rs/Opioid Withdrawal/Ach system, in the present paper we have designed six new CB1Rs agonists named A-F and evaluated their role in mediating morphine withdrawal in GPI. Also, a comparative study was performed by using the CB1Rs synthetic cannabinoid WIN 55,212-2 and CP 55,940. The results of our experiments indicate that both WIN 55,212-2 and CP 55,940 (1x10(-8)-5x10(-8)-1x10(-7) M) were able to reduce morphine withdrawal in a concentration-dependent manner. Very similar results were obtained with the new CB1Rs agonists (A-F) used at same concentrations. The results of our experiments indicate that CB1Rs are involved in the control of morphine withdrawal in vitro thus confirming an important functional interaction between the cannabinoid and opioid system.
Effects of red grape juice consumption on high density lipoprotein-cholesterol, apolipoprotein AI, apolipoprotein B and homocysteine in healthy human volunteers.
Khadem-Ansari MH, Rasmi Y, Ramezani F
Open Biochem J · 2010 · PMID 21633724 · Full text
It has suggested that grape juice consumption has lipid- lowering effect and it is associated with a decreased risk of heart disease. We aimed to evaluate the effects of red grape juice (RGj) consumption on high density...
It has suggested that grape juice consumption has lipid- lowering effect and it is associated with a decreased risk of heart disease. We aimed to evaluate the effects of red grape juice (RGj) consumption on high density lipoprotein-cholesterol (HDL-C), apolipoprotein AI (apoAI), apolipoprotein B (apoB) and homocysteine (Hcy) levels in healthy human volunteers. Twenty six healthy and nonsmoking males, aged between 25-60 years, who were under no medication asked to consume 150 ml of RGj twice per day for one month. Serum HDL-C, apoAI, apoB and plasma Hcy levels were measured before and after one month RGj consumption. HDL-C levels after RGj consumption were significantly higher than the corresponding levels before the RGj consumption (41.44 ± 4.50 and 44.37 ± 4.30 mg/dl; P<0.0001). Also, apoB was significantly increased after RGj consumption (149.0 ± 22.35 and 157.19 ± 18.60 mg/dl; P<0.002). But apoAI levels were not changed significantly before and after of RGj consumption (154.27 ± 21.55 and 155.35 ± 21.07 mg/dl; P>0.05). Hcy levels were decreased after RGj consumption (7.70 ± 2.80 and 6.20 ± 2.30 µmol/l; P<0.001). The present study demonstrates that RGj consumption can significantly increase serum HDL-C levels and decrease Hcy levels. These findings may have important implications for the prevention of atherosclerosis in healthy individuals.
Coordination between nitric oxide and superoxide anion radical during progressive exercise in elite soccer players.
Djordjevic D, Jakovljevic V, Cubrilo D … +3 more , Zlatkovic M, Zivkovic V, Djuric D
Open Biochem J · 2010 · PMID 21633721 · Full text
BACKGROUND: Exercise increases production of reactive oxygen and nitrogen species (RONS) via several mechanisms. Inter alia, increased blood flow during exercise exposes endothelial cells to shear stress, resulting in in...
BACKGROUND: Exercise increases production of reactive oxygen and nitrogen species (RONS) via several mechanisms. Inter alia, increased blood flow during exercise exposes endothelial cells to shear stress, resulting in increased nitric oxide (NO) production. Increased oxygen consumption or hypoxia during exercise induces increased production of superoxide anion radical (O(2) (-)). OBJECTIVE: This study investigates the effects of maximal progressive treadmill exercise test on time-course of peripheral blood NO and O(2) (-) production, as well as the effect of long-term training on NO bioavailability. METHODS: Blood samples of 19 elite soccer players were gathered immediately before the test, during last 10 sec of every test stage, and during active recovery phases. RESULTS: Significant increase (p<0.05) in NO production (estimated through nitrites (NO(2) (-))), found between stage I (5.69 ± 1.32 nmol/ml) and basal values (5.36 ± 1.25 nmol/ml), was followed by the decrease in stage II (4.21 ± 0.42 nmol/ml) and production lower than basal to the end of the test. Significant increase (p<0.05) in O(2) (-) values was found between stage I (4.18 ± 0.77 nmol/ml) and resting values (4.01 ± 0.69 nmol/ml), and at stages V (4.24 ± 0.85 nmol/ml) and 1st phase of recovery (4.39 ± 0.92 nmol/ml). CONCLUSION: The regression lines of NO(2) (-) and O(2) (-) crossed at the level of anaerobic threshold, suggesting that anaerobic threshold could be of a crucial importance not only in the anaerobic and aerobic metabolism but in mechanisms of signal transductions as well. Long-term exercise increases NO bioavailability, and there is positive correlation between NO bioavailability and maximal oxygen uptake (VO(2max)).
Multiple Unfolding Intermediates Obtained by Molecular Dynamic Simulations under Stretching for Immunoglobulin-Binding Domain of Protein G.
Glyakina AV, Balabaev NK, Galzitskaya OV
Open Biochem J · 2009 Nov · PMID 20037652 · Full text
We have studied the mechanical properties of the immunoglobulin-binding domain of protein G at the atomic level under stretching at constant velocity using molecular dynamics simulations. We have found that the unfolding...
We have studied the mechanical properties of the immunoglobulin-binding domain of protein G at the atomic level under stretching at constant velocity using molecular dynamics simulations. We have found that the unfolding process can occur either in a single step or through intermediate states. Analysis of the trajectories from the molecular dynamic simulations showed that the mechanical unfolding of the immunoglobulin-binding domain of protein G is triggered by the separation of the terminal beta-strands and the order in which the secondary-structure elements break is practically the same in two- and multi-state events and at the different extension velocities studied. It is seen from our analysis of 24 trajectories that the theoretical pathway of mechanical unfolding for the immunoglobulin-binding domain of protein G does not coincide with that proposed in denaturant studies in the absence of force.
The role of exercise on L-arginine nitric oxide pathway in chronic heart failure.
Mendes-Ribeiro AC, Mann GE, de Meirelles LR … +3 more , Moss MB, Matsuura C, Brunini TM
Open Biochem J · 2009 Oct · PMID 19911071 · Full text
Chronic heart failure (CHF) is a pathological state with high morbidity and mortality and the full understanding of its genesis remain to be elucidated. In this syndrome, a cascade of neurohormonal and hemodynamic mechan...
Chronic heart failure (CHF) is a pathological state with high morbidity and mortality and the full understanding of its genesis remain to be elucidated. In this syndrome, a cascade of neurohormonal and hemodynamic mechanisms, as well as inflammatory mediators, are activated to improve the impaired cardiac function. Clinical and experimental observations have shown that CHF is associated with a generalized disturbance in endothelium-dependent vasodilation, which may contribute to the progression of ventricular and vascular remodelling in this syndrome. There is also accumulating evidence that disturbances in nitric oxide (NO) availability is involved in the development of heart failure at the systemic and cardiac levels. NO is a ubiquitous signalling molecule which causes potent vasodilation, inhibits platelet activation and regulates the contractile properties of cardiac myocytes. It is generated from the amino acid L-arginine via constitutive and inducible isoforms of the enzyme NO synthase (NOS). There is evidence that exercise, a nonpharmacological tool, improves symptoms, fitness (VO(2peak)), quality of life and NO bioavailability in CHF population. This review examines different aspects of the L-arginine-NO pathway and inflammation in the physiopathology of CHF and highlights the important beneficial effects of exercise in this disease.
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