The Open Biochemistry Journal[JOURNAL]
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130 papers
Coherent Behavior and the Bound State of Water and K(+) Imply Another Model of Bioenergetics: Negative Entropy Instead of High-energy Bonds.
Jaeken L, Vasilievich Matveev V
Open Biochem J · 2012 · PMID 23264833 · Full text
Observations of coherent cellular behavior cannot be integrated into widely accepted membrane (pump) theory (MT) and its steady state energetics because of the thermal noise of assumed ordinary cell water and freely solu...
Observations of coherent cellular behavior cannot be integrated into widely accepted membrane (pump) theory (MT) and its steady state energetics because of the thermal noise of assumed ordinary cell water and freely soluble cytoplasmic K(+). However, Ling disproved MT and proposed an alternative based on coherence, showing that rest (R) and action (A) are two different phases of protoplasm with different energy levels. The R-state is a coherent metastable low-entropy state as water and K(+) are bound to unfolded proteins. The A-state is the higher-entropy state because water and K(+) are free. The R-to-A phase transition is regarded as a mechanism to release energy for biological work, replacing the classical concept of high-energy bonds. Subsequent inactivation during the endergonic A-to-R phase transition needs an input of metabolic energy to restore the low entropy R-state. Matveev's native aggregation hypothesis allows to integrate the energetic details of globular proteins into this view.
Biochemical and computational approaches to improve the clinical treatment of dopa decarboxylase-related diseases: an overview.
Cellini B, Montioli R, Oppici E … +1 more , Voltattorni CB
Open Biochem J · 2012 · PMID 23264832 · Full text
Dopa decarboxylase (DDC) is a pyridoxal 5'-phosphate (PLP)-dependent enzyme that by catalyzing the decarboxylation of L-Dopa and L-5-hydroxytryptophan produces the neurotransmitters dopamine and serotonin. The functional...
Dopa decarboxylase (DDC) is a pyridoxal 5'-phosphate (PLP)-dependent enzyme that by catalyzing the decarboxylation of L-Dopa and L-5-hydroxytryptophan produces the neurotransmitters dopamine and serotonin. The functional properties of pig kidney and human DDC enzymes have been extensively characterized, and the crystal structure of the enzyme in the holo- and apo-forms has been elucidated. DDC is a clinically relevant enzyme since it is involved in Parkinson's disease (PD) and in aromatic amino acid decarboxylase (AADC) deficiency. PD, a chronic progressive neurological disorder characterized by tremor, bradykinesia, rigidity and postural instability, results from the degeneration of dopamine-producing cells in the substantia nigra of the brain. On the other hand, AADC deficiency is a rare debilitating recessive genetic disorder due to mutations in AADC gene leading to the inability to synthesize dopamine and serotonin. Development delay, abnormal movements, oculogyric crises and vegetative symptoms characterize this severe neurometabolic disease. This article is an up to date review of the therapies currently used in the treatment of PD and AADC deficiency as well as of the recent findings that, on one hand provide precious guidelines for the drug development process necessary to PD therapy, and, on the other, suggest an aimed therapeutic approach based on the elucidation of the molecular defects of each variant associated with AADC deficiency.
Characterization of Carotenoid-protein Complexes and Gene Expression Analysis Associated with Carotenoid Sequestration in Pigmented Cassava (Manihot Esculenta Crantz) Storage Root.
Carvalho LJ, Lippolis J, Chen S … +3 more , Batista de Souza CR, Vieira EA, Anderson JV
Open Biochem J · 2012 · PMID 23230451 · Full text
Carotenoid-protein complex (CPC) was isolated from chromoplast-enriched suspensions of cassava storage root (CSR) using size exclusion chromatography and characterized. Peptide sequences (LC_MS/MS spectrum) obtained from...
Carotenoid-protein complex (CPC) was isolated from chromoplast-enriched suspensions of cassava storage root (CSR) using size exclusion chromatography and characterized. Peptide sequences (LC_MS/MS spectrum) obtained from CPC and their corresponding proteins were obtained using publically available databases. Small Heat Shock Proteins (sHSPs) were the most abundant proteins identified in the CPC. Western blot analysis showed that Fribrillin and Or-protein were present in chromoplast-enriched suspensions of yellow root but not in the complex or white root. Results from qRT-PCR helped identify an isoform of HSP21 possessing four single point mutations in the intense yellow CSR that may be responsible for increased sequestration of b-carotene.
Transcriptional and secretomic profiling of epidermal cells exposed to alpha particle radiation.
Chauhan V, Howland M, Greene HB … +1 more , Wilkins RC
Open Biochem J · 2012 · PMID 23002402 · Full text
Alpha (α)-particle emitters are probable isotopes to be used in a terrorist attack. The development of biological assessment tools to identify those who have handled these difficult to detect materials would be an asset...
Alpha (α)-particle emitters are probable isotopes to be used in a terrorist attack. The development of biological assessment tools to identify those who have handled these difficult to detect materials would be an asset to our current forensic capacity. In this study, for the purposes of biomarker discovery, human keratinocytes were exposed to α-particle and X-radiation (0.98 Gy/h at 0, 0.5, 1.0, 1.5 Gy) and assessed for differential gene and protein expression using microarray and Bio-Plex technology, respectively. Secretomic analysis of supernatants showed expression of two pro-inflammatory cytokines (IL-13 and PDGF-bb) to be exclusively affected in α-particle exposed cells. The highest dose of α-particle radiation modulated a total of 67 transcripts (fold change>|1.5|, (False discovery rate) FDR<0.05) in exposed cells. Several genes which responded with high expression levels (>2 fold) included KIF20A, NEFM, C7orf10, HIST1H2BD, BMP6, and HIST1H2AC. Among the high expressing genes, five (CCNB2, BUB1, NEK2, CDC20, AURKA) were also differentially expressed at the medium (1.0 Gy) dose however, these genes were unmodulated following exposure to X-irradiation. Networks of these genes clustered around tumor protein-53 and transforming growth factor-beta signaling. This study has identified some potential gene /protein responses and networks that may be validated further to confirm their specificity and potential to be signature biomarkers of α-particle exposure.
Model of Abnormal Chromophore-Protein Interaction for Е181К Rhodopsin Mutation: Computer Molecular Dynamics Study.
Feldman T, Ostrovsky M, Kholmurodov K … +1 more , Yasuoka K
Open Biochem J · 2012 · PMID 22930661 · Full text
The interaction of the 11-cis-retinal chromophore with the surrounding amino acid residues in the chromophore center of the rhodopsin protein has been investigated for the Е181К mutant form using molecular dynamics simul...
The interaction of the 11-cis-retinal chromophore with the surrounding amino acid residues in the chromophore center of the rhodopsin protein has been investigated for the Е181К mutant form using molecular dynamics simulation. A comparative analysis of the arrangement of the amino acid residues in the chromophore center has been performed for both wild (native) and mutant rhodopsins. It is shown that for the Е181К mutant rhodopsin there is no proper binding of 11-cis-retinal with the surrounding amino acid residues. The distortion of the conformation states in the mutant rhodopsin molecule takes place in both the chromophore center and cytoplasmic domain. Our simulations suggest that a stable covalent linkage of 11-cis-retinal with the protein part (viz. opsin) of the rhodopsin molecule will not form. This, on the other hand, implies that the protein's active site in the cytoplasmic domain, which is responsible for the G-protein binding (so-called transducin), may not be completely blocked.Based on our molecular simulation data, we discuss the possible correlation between retinitis pigmentosa pathogenesis and the structural and functional properties of the rhodopsin protein.
High Density Lipoprotein and it's Dysfunction.
Eren E, Yilmaz N, Aydin O
Open Biochem J · 2012 · PMID 22888373 · Full text
Plasma high-density lipoprotein cholesterol(HDL-C) levels do not predict functionality and composition of high-density lipoprotein(HDL). Traditionally, keeping levels of low-density lipoprotein cholesterol(LDL-C) down an...
Plasma high-density lipoprotein cholesterol(HDL-C) levels do not predict functionality and composition of high-density lipoprotein(HDL). Traditionally, keeping levels of low-density lipoprotein cholesterol(LDL-C) down and HDL-C up have been the goal of patients to prevent atherosclerosis that can lead to coronary vascular disease(CVD). People think about the HDL present in their cholesterol test, but not about its functional capability. Up to 65% of cardiovascular death cannot be prevented by putative LDL-C lowering agents. It well explains the strong interest in HDL increasing strategies. However, recent studies have questioned the good in using drugs to increase level of HDL. While raising HDL is a theoretically attractive target, the optimal approach remains uncertain. The attention has turned to the quality, rather than the quantity, of HDL-C. An alternative to elevations in HDL involves strategies to enhance HDL functionality. The situation poses an opportunity for clinical chemists to take the lead in the development and validation of such biomarkers. The best known function of HDL is the capacity to promote cellular cholesterol efflux from peripheral cells and deliver cholesterol to the liver for excretion, thereby playing a key role in reverse cholesterol transport (RCT). The functions of HDL that have recently attracted attention include anti-inflammatory and anti-oxidant activities. High antioxidant and anti-inflammatory activities of HDL are associated with protection from CVD.This review addresses the current state of knowledge regarding assays of HDL functions and their relationship to CVD. HDL as a therapeutic target is the new frontier with huge potential for positive public health implications.
Histidine 117 in the His-Gly-Ser-Asp motif is Required for the Biochemical Activities of Nucleoside Diphosphate Kinase of Mycobacterium smegmatis.
Arumugam M, Ajitkumar P
Open Biochem J · 2012 · PMID 22888372 · Full text
Nucleoside diphosphate kinase (NDK), which is widely conserved in both prokaryotes and eukaryotes, maintains a balanced pool of nucleotide triphosphates and their deoxy derivatives. NDKs from bacterial and other systems...
Nucleoside diphosphate kinase (NDK), which is widely conserved in both prokaryotes and eukaryotes, maintains a balanced pool of nucleotide triphosphates and their deoxy derivatives. NDKs from bacterial and other systems contain the conserved HGSD motif, where the His residue is required for the biochemical activities, namely the NTPase (AT-Pase and GTPase), NTP synthesising, and autophosphorylation activities of the enzyme. Amino acid sequence homology comparison of the NDK of Mycobacterium smegmatis (MsmNDK) with the NDKs of other bacterial genera showed the presence of H(117)GSD motif. While the recombinant wild type MsmNDK showed the NTPase, NTP synthesising, and autophosphorylation activities, the H117Q mutation abolished the biochemical activities of the recombinant MsmNDK-H117Q mutant protein in vitro. These observations demonstrate that the H117 residue in the HGSD motif is required for the biochemical activities of MsmNDK.
Myricetin Inhibits Islet Amyloid Polypeptide (IAPP) Aggregation and Rescues Living Mammalian Cells from IAPP Toxicity.
Zelus C, Fox A, Calciano A … +3 more , Faridian BS, Nogaj LA, Moffet DA
Open Biochem J · 2012 · PMID 22792130 · Full text
The aggregation of the amyloidogenic polypeptide IAPP (Islet Amyloid Polypeptide, amylin) is believed to play a direct role in the death of pancreatic β-islet cells in type II diabetes. Preventing the initial aggregation...
The aggregation of the amyloidogenic polypeptide IAPP (Islet Amyloid Polypeptide, amylin) is believed to play a direct role in the death of pancreatic β-islet cells in type II diabetes. Preventing the initial aggregation event of IAPP is one strategy for slowing, and possibly preventing, the progression of this disease. Here, we investigate myricetin's potential as an inhibitor of IAPP aggregation. We show that myricetin prevented thioflavin T binding in a concentration dependent manner. Atomic force microscopy revealed that myricetin prevented fiber formation under rigorous conditions conducive to forming IAPP aggregates. Using an IAPP-EGFP (Enhanced Green Fluorescent Protein) protein construct, we find that high concentrations of myricetin slowed the in vivo aggregation of IAPP-EGFP. Myricetin was also found to rescue living mammalian cells from the toxic effects of IAPP. These results indicate that myricetin is a strong inhibitor of IAPP amyloid aggregation and a potential lead molecule for the development of an amyloid inhibiting therapeutic.
Tianma modulates blood vessel tonicity.
Feng L, Manavalan A, Mishra M … +3 more , Sze SK, Hu JM, Heese K
Open Biochem J · 2012 · PMID 22787517 · Full text
Tianma is a traditional Chinese medicine (TCM) often used for the treatment of hypertension and heart diseases. To elucidate the function of tianma at the molecular level, we investigated the effect of tianma on vascular...
Tianma is a traditional Chinese medicine (TCM) often used for the treatment of hypertension and heart diseases. To elucidate the function of tianma at the molecular level, we investigated the effect of tianma on vascular functions and aortic protein metabolism. We found that long-term treatment with tianma (~2.5g/kg/day for three months) in one-year-old rats could enhance acetylcholine (ACh)-induced vasorelaxation in endothelium-intact thoracic aortic rings against both KCl (80 mM)- and phenylephrine (PE)-induced contraction. By using the iTRAQ (isobaric tag for relative and absolute quantification) technique, we confirmed from the functional data at the proteome level that tianma treatment down-regulated the expressions of contractile proteins (e.g. Acta2) and other related structural proteins (e.g. desmin), and up-regulated the expressions of extracellular matrix (ECM) glycoproteins (e.g. Fbln5) and anti-thrombotic proteins (e.g. Anxa2) in aortic tissue. By inductive reasoning, tianma could perform its vasodilatory effect not only by inhibiting vascular smooth muscle contraction, but also by enhancing blood vessel elasticity and stabilizing the arterial structure. Thus, tianma might become a novel therapeutic herbal medicine for cardiovascular diseases by regulating the aortic proteome metabolism.
Effect of peppermint oil on serum lipid peroxidation and hepatic enzymes after immobility stress in mice.
Marjani A, Rahmati R, Mansourian AR … +1 more , Veghary G
Open Biochem J · 2012 · PMID 22654997 · Full text
This study was undertaken to determine the influences of various doses of peppermint oil on the hepatic en-zymes, alanine transaminase, apartate tranaminase, alkaline phosphotase and gamma glutamyl transferase and the le...
This study was undertaken to determine the influences of various doses of peppermint oil on the hepatic en-zymes, alanine transaminase, apartate tranaminase, alkaline phosphotase and gamma glutamyl transferase and the level of malondialdehyde in the serum of mice with and without immobility stress. The mice exposed to drink water, 0.9, 27 and 60 mg/kg peppermint oil from the days 1 to 5 for a period of 4 h before and after immobility stress. Serum MDA in-creased in treatment group II, III and IV after immobility stress. There was a significant decrease in ALT in treatment group III and IV after immobility stress. There were also significant decreases in ALP and GGT in treatment group IV af-ter immobility stress. This result may suggest that, MDA level is higher in immobilization stress group than in the un-immobilized animals in serum and this results show that enzyme activities decreased after immobilization stress.
Cardiovascular risk factors in portuguese obese children and adolescents: impact of small reductions in body mass index imposed by lifestyle modifications.
Nascimento H, Costa E, Rocha-Pereira P … +5 more , Rego C, Mansilha HF, Quintanilha A, Santos-Silva A, Belo L
Open Biochem J · 2012 · PMID 22629286 · Full text
OBJECTIVES: Evaluate cardiovascular risk factors in Portuguese obese children and adolescents and the long-term effects of lifestyle modifications on such risk factors. DESIGN: Transversal cohort study and longitudinal s...
OBJECTIVES: Evaluate cardiovascular risk factors in Portuguese obese children and adolescents and the long-term effects of lifestyle modifications on such risk factors. DESIGN: Transversal cohort study and longitudinal study. SETTING: University Hospital S. João and Children's Hospital Maria Pia, Porto. PATIENTS/PARTICIPANTS: 148 obese children and adolescents [81 females (54.7%); mean age of 11.0 years] and 33 controls (sex and age matched) participated in a cross-sectional study. Sixty obese patients agreed to participate in an one year longitudinal study after medical and nutritionist appointments to improve lifestyle modification; a substantial body mass index (BMI) reduction was defined by a decrease in BMI z-score (BMI z-sc) of 0.3 or more over the studied period. MAIN OUTCOME MEASURES: Lipid profile (triglycerides, cholesterol, HDLc, LDLc, lipoprotein (a), apolipoproteins A and B) and circulating levels of C-reactive protein (CRP), adiponectin, glucose, and insulin. RESULTS: Compared with the lean children, obese patients demonstrated statistically significantly higher insulin resistance index [Homeostasis model assessment (HOMA)], and triglycerides, LDLc, apolipoprotein (apo) B, insulin and CRP concentrations, whereas their HDLc and apo A levels were significantly lower (cross-sectional study). In the longitudinal study (n=60), a substantial BMI reduction occurred in 17 (28.3%) obese patients which led to a significant reduction in triglycerides, cholesterol, LDLc, apo B, glucose and insulin levels and in HOMA. The ΔBMI values over the studied period correlated inversely and significantly with BMI (P<0.001) and HOMA (P=0.026) values observed at baseline. In multiple linear regression analysis, BMI at baseline remained associated to changes in BMI over the studied period (standardised Beta: -0.271, P=0.05). CONCLUSION: Our data demonstrates that small reductions in BMI-zc, imposed by lifestyle modifications in obese children and adolescents, improve the cardiovascular risk profile of such patients. Furthermore, patients with higher BMI and/or insulin resistance seem to experience a greater relative reduction in their BMI after lifestyle improvements.
Hypothetical two-step initiation of experimental carcinogenesis by polycyclic aromatic hydrocarbons and aminoazo dyes.
Contag B
Open Biochem J · 2012 · PMID 22582097 · Full text
A new hypothesis is discussed, which describes the initiation of the carcinogenesis through polycyclic aromatic hydrocarbons (PAHs) and aminoazo dyes (AZOs) as a two-step process: the oncogenic proteins of the ras or ras...
A new hypothesis is discussed, which describes the initiation of the carcinogenesis through polycyclic aromatic hydrocarbons (PAHs) and aminoazo dyes (AZOs) as a two-step process: the oncogenic proteins of the ras or ras-like on-cogenes activated by mutation ("initiation A ") co-operate with the complexes in the plasma membrane formed during the "initiation B " stage from the parent compounds of the PAHs or AZOs with cholesterol and apolipoprotein A-I. The final result of this co-operation, or the "complete initiation", is an irreversibly modified membrane architecture with negative consequences for growth control.
Effects of nerve growth factor and nitric oxide synthase inhibitors on amyloid precursor protein mRNA levels and protein stability.
Mackinnon JC, Huether P, Kalisch BE
Open Biochem J · 2012 · PMID 22550546 · Full text
We determined previously that nitric oxide (NO) modulates the nerve growth factor (NGF)-mediated increases in amyloid precursor protein (APP) levels in PC12 cells. To elucidate potential mechanisms, the effects of NGF an...
We determined previously that nitric oxide (NO) modulates the nerve growth factor (NGF)-mediated increases in amyloid precursor protein (APP) levels in PC12 cells. To elucidate potential mechanisms, the effects of NGF and NO synthase (NOS) inhibitors on APP mRNA levels and protein stability were evaluated. Surprisingly, treatment of PC12 cells with NGF resulted in decreased levels of APP695 and APP751/770 mRNA. Therefore, the effect of NGF on APP protein stability was examined using the translation inhibitor, cycloheximide. Under these conditions, NGF did not alter the rate of APP degradation, suggesting that NGF may be enhancing the translation rate of APP. Since NOS inhibitors attenuate the NGF-mediated increase in APP levels, their effect on APP mRNA levels and protein stability was also assessed. S-methylisothiourea (S-MIU), selective for inducible NOS, decreased both APP695 and APP751/770 mRNA levels while the non-selective NOS inhibitor, N(ω)-nitro-L-arginine methylester (L-NAME) had no effect. In both control and NGF-treated PC12 cells, S-MIU increased the half-life of APP, with the greatest effect observed with the APP695 isoform. Based on these data we propose that in PC12 cells, NGF increases APP levels through enhanced translation rate and that NO, which modulates the NGF-induced increase in APP protein, also regulates APP mRNA levels and could play a role in APP processing.
Protein Kinase A Subunit α Catalytic and A Kinase Anchoring Protein 79 in Human Placental Mitochondria.
Ma MP, Thomson M
Open Biochem J · 2012 · PMID 22529880 · Full text
Components of protein phosphorylation signalling systems have been discovered in mitochondria and it has been proposed that these molecules modulate processes including oxidative phosphorylation, apoptosis and steroidoge...
Components of protein phosphorylation signalling systems have been discovered in mitochondria and it has been proposed that these molecules modulate processes including oxidative phosphorylation, apoptosis and steroidogenesis. We used electrophoresis and Western blots probed with specific antibodies to protein kinase A α catalytic subunit (PKAα Cat) and A kinase anchoring protein of approximately 79 kDa molecular weight (AKAP79) to demonstrate the presence of these two proteins in human placental mitochondria. Heavy mitochondria characteristic of cytotrophoblast were separated from light mitochondria characteristic of syncytiotrophoblast by centrifugation. PKAα Cat and AKAP79 were present in both heavy and light mitochondria with no significant difference in concentration. Sucrose density gradient separation of submitochondrial fractions indicated PKAα Cat is located predominantly in the outer membrane whereas AKAP79 is present mainly in the contact site fractions. These data indicate that PKAα Cat is present in the cytoplasm, nucleus and mitochondria of placental cells. AKAP79 is also present in human placental mitochondria but there may be anchoring proteins other than AKAP79 responsible for fixing PKA to the outer membrane. PKA may play roles in mitochondrial protein phosphorylation systems in both cytotrophoblast and syncytiotrophoblast.
Effects of α-Particle Radiation on MicroRNA Responses in Human Cell-Lines.
Chauhan V, Howland M, Wilkins R
Open Biochem J · 2012 · PMID 22481983 · Full text
A variety of alpha (α)-particle emitters are found ubiquitously in the environment, in commercial/therapeutic prod-ucts and are a potential threat in the form of a radiological dispersal device. Our understanding of the...
A variety of alpha (α)-particle emitters are found ubiquitously in the environment, in commercial/therapeutic prod-ucts and are a potential threat in the form of a radiological dispersal device. Our understanding of the biological mechanisms and long-term health effects resulting from α-particle exposure is limited. Exposure to radiation induces modulations of gene networks, possibly through microRNAs (miRNAs), which could be targets for studying biological effects. In this study, changes in miRNA expression patterns after 0.5 Gy, 1.0 Gy and 1.5 Gy of α-particle radiation at a low dose-rate of exposure in three human cell-lines (A549, THP-1 and HFL) were investigated. The screening of 1,145 miRNAs across three human cell-lines resulted in unique, cell-specific responses with no overlap in miRNA expression observed in the three cell-lines. Prediction analysis suggests these α-particle induced miRNA mapped to target genes related to ribosomal assembly, lung carcinoma development, cell communication and keratin sulfate biosynthesis. Taken together, these results suggest that exposure to α-particle radiation results in cell-type specific responses in gene network regulatory processes.
Gossypol Inhibits Electron Transport and Stimulates ROS Generation in Yarrowia lipolytica Mitochondria.
Arinbasarova AY, Medentsev AG, Krupyanko VI
Open Biochem J · 2012 · PMID 22481982 · Full text
This work studied the effect of gossypol on the mitochondrial respiratory chain of Yarrowia lipolytica. The compound was shown to inhibit mitochondrial electron transfer and stimulate generation of reactive oxygen specie...
This work studied the effect of gossypol on the mitochondrial respiratory chain of Yarrowia lipolytica. The compound was shown to inhibit mitochondrial electron transfer and stimulate generation of reactive oxygen species. The inhibition kinetics in oxidation of various substrates (NADH, succinate, α-glycerophosphate and pyruvate + malate) by isolated mitochondria was investigated. Analysis of the kinetic parameters showed gossypol to inhibit two fragments of the mitochondrial electron transfer chain: a) between coenzyme Q and cytochrome b with K(IIIi) of 118.3 μM (inhibition by the noncompetitive type), and b) at the level of exogenous NADH dehydrogenase with of K(Ii) 17.2 μM (inhibition by the mixed type).
Endoplasmic Reticulum (ER) Stress Enhances Tip60 (A Histone Acetyltransferase) Binding to the Concanavalin A.
Lee EJ, Shin SH, Hyun S … +2 more , Chun J, Kang SS
Open Biochem J · 2012 · PMID 22448206 · Full text
Herein, we report that the concanavalin A binding of Tip60 (a target of the human immunodeficiency virus type 1-encoded transactivator Tat interacting protein 60 KD; a histone acetyltransferase; HAT) is enhanced as the r...
Herein, we report that the concanavalin A binding of Tip60 (a target of the human immunodeficiency virus type 1-encoded transactivator Tat interacting protein 60 KD; a histone acetyltransferase; HAT) is enhanced as the result of endoplasmic reticulum (ER) stress. The cell expression of Tip60 combined with site-directed mutagenesis analysis was used to identify the glutamine 324 residue as the lecithin binding (Concanavalin A; Con A) site. The Tip60 N324A mutant strain, which seems to be the Con A binding-deficient, was attenuated the protein-protein interactions with FE65 and its protein stability, but its ability of G0-G1 cell cycle arrest was not interrupted. Interestingly, both HAT activity and the nuclear localization of Tip60 N324A mutant were enhanced than those of Tip60 WT. Thus, our results indicate that the Con A binding deficient of Tip60 seems to be one of the most pivotal posttranslational modifications (such as N-glycosylation) for its functional regulation signal, which is generated in response to ER stress.
Distinct metal ion requirements for the phosphomonoesterase and phosphodiesterase activities of calf intestinal alkaline phosphatase.
Igunnu A, Osalaye DS, Olorunsogo OO … +2 more , Malomo SO, Olorunniji FJ
Open Biochem J · 2011 · PMID 22262982 · Full text
The roles of Mg(2+) and Zn(2+) ions in promoting phosphoryl transfer catalysed by alkaline phosphatase are yet to be fully characterised. We investigated the divalent metal ion requirements for the monoesterase and diest...
The roles of Mg(2+) and Zn(2+) ions in promoting phosphoryl transfer catalysed by alkaline phosphatase are yet to be fully characterised. We investigated the divalent metal ion requirements for the monoesterase and diesterase activities of calf intestinal alkaline phosphatase. The synergistic effect of Mg(2+) and Zn(2+) in promoting the hydrolysis of para-nitrophenyl phosphate (monoesterase reaction) by alkaline phosphatase is not observed in the hydrolysis of the diesterase substrate, bis-para-nitrophenyl phosphate. Indeed, the diesterase reaction is inhibited by concentrations of Mg(2+) that were optimal for the monoesterase reaction. This study reveals that the substrate specificities of alkaline phosphatases and related bimetalloenzymes are subject to regulation by changes in the nature and availability of cofactors, and the different cofactor requirements of the monoesterase and diesterase reactions of mammalian alkaline phosphatases could have significance for the biological functions of the enzymes.
New Perspectives of "omics" Applications in Melanoma Research.
Rodríguez-Cerdeira C, Molares-Vila A
Open Biochem J · 2011 · PMID 22253648 · Full text
BACKGROUND: Oncoproteomics is the study of proteins and their interactions in a cancer cell by proteomic technologies and has the potential to revolutionize clinical practice, including cancer diagnosis. Recent technolog...
BACKGROUND: Oncoproteomics is the study of proteins and their interactions in a cancer cell by proteomic technologies and has the potential to revolutionize clinical practice, including cancer diagnosis. Recent technological advances in the analysis of the human genome have opened the door to improving our primitive understanding of the gene expression patterns in cancer. The examination of the phenotypic and (epi) genetic changes in cutaneous melanoma has identified several genes deemed central to the development and progression of melanoma. METHODS: A review of the literature was performed to determine the role of epigenetic modifications in human melanoma. The role of array-based high-throughput gene expression analysis in understanding the specific genes involved as well as the pathways and the comparative gene expression patterns of primary and metastatic melanoma. The development and clinical application of selective pharmacologic agents are also discussed. RESULTS: We identified several articles that have extensively studied the role of epigenetics in melanoma, further elucidating the complex processes involved in gene regulation and expression. Other studies utilizing gene microarray analysis and other whole genome approaches reveal a wide array of genes and expression patterns in human melanoma. Several genes have been identified as potential prognostic markers of tumor progression and overall clinical outcome. CONCLUSIONS: High-throughput gene expression analysis has had a major impact in melanoma research. Several gene expression platforms have provided insight into the gene expression patterns in melanoma. Such data will provide foundations for the future development of prognostic markers and improved targeted therapies for patients with melanoma.
Production of free radicals and oxygen consumption by primary equine endothelial cells during anoxia-reoxygenation.
de Rebière de Pouyade G, Salciccia A, Ceusters J … +3 more , Deby-Dupont G, Serteyn D, Mouithys-Mickalad A
Open Biochem J · 2011 · PMID 22207886 · Full text
The endothelium plays an active role in ischemia/reperfusion injuries. Herein, we report the effect of a single or successive cycles of anoxia/reoxygenation (A/R) on the mitochondrial respiratory function of equine endot...
The endothelium plays an active role in ischemia/reperfusion injuries. Herein, we report the effect of a single or successive cycles of anoxia/reoxygenation (A/R) on the mitochondrial respiratory function of equine endothelial cells (cultured from carotids) monitored by high resolution oxymetry, and on their production of reactive oxygen species (ROS). ROS were measured by electron paramagnetic resonance (ESR) using POBN and DMPO spin traps, and by gas chromatography (GC) of ethylene released by ROS-induced α-keto-γ-(methylthio)butyric acid (KMB) oxidation. The oxygen consumption significantly decreased with the number of A/R cycles, and POBN-ESR spectra were specific of adducts formed in the cells from superoxide anion. After a one-hour A/R cycle, high intensity DMPO-ESR spectra were observed and assigned to superoxide anion trapping; the GC results confirmed an important production of ROS compared to normoxic cells. These results show that A/R induces mitochondrial alterations in endothelial cells, and strongly stimulates their oxidative activity as demonstrated by ESR and GC methods.
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