World Journal Of Biological Chemistry[JOURNAL]
Sun
200 papers
Neuroprotection by dipeptidyl-peptidase-4 inhibitors and glucagon-like peptide-1 analogs the modulation of AKT-signaling pathway in Alzheimer's disease.
Ikeda Y, Nagase N, Tsuji A … +2 more , Kitagishi Y, Matsuda S
World J Biol Chem · 2021 Nov · PMID 34904048 · Full text
Alzheimer's disease (AD) is the most common reason for progressive dementia in the elderly. It has been shown that disorders of the mammalian/mechanistic target of rapamycin (mTOR) signaling pathways are related to the A...
Alzheimer's disease (AD) is the most common reason for progressive dementia in the elderly. It has been shown that disorders of the mammalian/mechanistic target of rapamycin (mTOR) signaling pathways are related to the AD. On the other hand, diabetes mellitus (DM) is a risk factor for the cognitive dysfunction. The pathogenesis of the neuronal impairment caused by diabetic hyperglycemia is intricate, which contains neuro-inflammation and/or neurodegeneration and dementia. Glucagon-like peptide-1 (GLP1) is interesting as a possible link between metabolism and brain impairment. Modulation of GLP1 activity can influence amyloid-beta peptide aggregation the phosphoinositide-3 kinase/AKT/mTOR signaling pathway in AD. The GLP1 receptor agonists have been shown to have favorable actions on the brain such as the improvement of neurological deficit. They might also exert a beneficial effect with refining learning and memory on the cognitive impairment induced by diabetes. Recent experimental and clinical evidence indicates that dipeptidyl-peptidase-4 (DPP4) inhibitors, being currently used for DM therapy, may also be effective for AD treatment. The DPP-4 inhibitors have demonstrated neuroprotection and cognitive improvements in animal models. Although further studies for mTOR, GLP1, and DPP4 signaling pathways in humans would be intensively required, they seem to be a promising approach for innovative AD-treatments. We would like to review the characteristics of AD pathogenesis, the key roles of mTOR in AD and the preventive and/ or therapeutic suggestions of directing the mTOR signaling pathway.
Alcoholic liver disease: Current insights into cellular mechanisms.
Petagine L, Zariwala MG, Patel VB
World J Biol Chem · 2021 Sep · PMID 34630912 · Full text
Alcoholic liver disease (ALD) due to chronic alcohol consumption is a significant global disease burden and a leading cause of mortality. Alcohol abuse induces a myriad of aberrant changes in hepatocytes at both the cell...
Alcoholic liver disease (ALD) due to chronic alcohol consumption is a significant global disease burden and a leading cause of mortality. Alcohol abuse induces a myriad of aberrant changes in hepatocytes at both the cellular and molecular level. Although the disease spectrum of ALD is widely recognized, the precise triggers for disease progression are still to be fully elucidated. Oxidative stress, mitochondrial dysfunction, gut dysbiosis and altered immune system response plays an important role in disease pathogenesis, triggering the activation of inflammatory pathways and apoptosis. Despite many recent clinical studies treatment options for ALD are limited, especially at the alcoholic hepatitis stage. We have therefore reviewed some of the key pathways involved in the pathogenesis of ALD and highlighted current trials for treating patients.
Culprits or consequences: Understanding the metabolic dysregulation of muscle in diabetes.
O'Reilly CL, Uranga S, Fluckey JD
World J Biol Chem · 2021 Sep · PMID 34630911 · Full text
The prevalence of type 2 diabetes (T2D) continues to rise despite the amount of research dedicated to finding the culprits of this debilitating disease. Skeletal muscle is arguably the most important contributor to gluco...
The prevalence of type 2 diabetes (T2D) continues to rise despite the amount of research dedicated to finding the culprits of this debilitating disease. Skeletal muscle is arguably the most important contributor to glucose disposal making it a clear target in insulin resistance and T2D research. Within skeletal muscle there is a clear link to metabolic dysregulation during the progression of T2D but the determination of culprits consequences of the disease has been elusive. Emerging evidence in skeletal muscle implicates influential cross talk between a key anabolic regulatory protein, the mammalian target of rapamycin (mTOR) and its associated complexes (mTORC1 and mTORC2), and the well-described canonical signaling for insulin-stimulated glucose uptake. This new understanding of cellular signaling crosstalk has blurred the lines of what is a culprit and what is a consequence with regard to insulin resistance. Here, we briefly review the most recent understanding of insulin signaling in skeletal muscle, and how anabolic responses favoring anabolism directly impact cellular glucose disposal. This review highlights key cross-over interactions between protein and glucose regulatory pathways and the implications this may have for the design of new therapeutic targets for the control of glucoregulatory function in skeletal muscle.
Proteomics: Concepts and applications in human medicine.
Al-Amrani S, Al-Jabri Z, Al-Zaabi A … +2 more , Alshekaili J, Al-Khabori M
World J Biol Chem · 2021 Sep · PMID 34630910 · Full text
Proteomics is the complete evaluation of the function and structure of proteins to understand an organism's nature. Mass spectrometry is an essential tool that is used for profiling proteins in the cell. However, biomark...
Proteomics is the complete evaluation of the function and structure of proteins to understand an organism's nature. Mass spectrometry is an essential tool that is used for profiling proteins in the cell. However, biomarker discovery remains the major challenge of proteomics because of their complexity and dynamicity. Therefore, combining the proteomics approach with genomics and bioinformatics will provide an understanding of the information of biological systems and their disease alteration. However, most studies have investigated a small part of the proteins in the blood. This review highlights the types of proteomics, the available proteomic techniques, and their applications in different research fields.
Stem cells and the pursuit of youth, a tale of limitless possibilities and commercial fraud.
Al-Sowayan BS, Al-Shareeda AT
World J Biol Chem · 2021 Jul · PMID 34354805 · Full text
This article examines the hype generated around the term "stem cell", and the capitalization of the stem cell craze by the cosmetic industry. It started by introducing product lines containing active ingredients derived...
This article examines the hype generated around the term "stem cell", and the capitalization of the stem cell craze by the cosmetic industry. It started by introducing product lines containing active ingredients derived from plant stem cells. Then, evolved to using own cells for skin regeneration and hair loss treatment, and allogenic cells for the manufacturing of stem cell-derived products. This article also discusses the missing links for safe and reliable stem cell applications in cosmetics, and why local regulatory bodies, members of the industry and consumers must all work together to stop the illegitimate use of the "stem cell" good name in unsafe or fraudulent commercial practices.
Polyglutamylase activity of tubulin tyrosine ligase-like 4 is negatively regulated by the never in mitosis gene A family kinase never in mitosis gene A -related kinase 5.
Melo-Hanchuk TD, Kobarg J
World J Biol Chem · 2021 May · PMID 34084286 · Full text
BACKGROUND: Tubulins, building blocks of microtubules, are modified substrates of diverse post-translational modifications including phosphorylation, polyglycylation and polyglutamylation. Polyglutamylation of microtubul...
BACKGROUND: Tubulins, building blocks of microtubules, are modified substrates of diverse post-translational modifications including phosphorylation, polyglycylation and polyglutamylation. Polyglutamylation of microtubules, catalyzed by enzymes from the tubulin tyrosine ligase-like (TTLL) family, can regulate interactions with molecular motors and other proteins. Due to the diversity and functional importance of microtubule modifications, strict control of the TTLL enzymes has been suggested. AIM: To characterize the interaction between never in mitosis gene A-related kinase 5 (NEK5) and TTLL4 proteins and the effects of TTLL4 phosphorylation. METHODS: The interaction between NEK5 and TTLL4 was identified by yeast two-hybrid screening using the C-terminus of NEK5 (a.a. 260-708) as bait and confirmed by immunoprecipitation. The phosphorylation sites of TTLL4 were identified by mass spectrometry and point mutations were introduced. RESULTS: Here, we show that NEK5 interacts with TTLL4 and regulates its polyglutamylation activity. We further show that NEK5 can also interact with TTLL5 and TTLL7. The silencing of NEK5 increases the levels of polyglutamylation of proteins by increasing the activity of TTLL4. The same effects were observed after the expression of the catalytically inactive form of NEK5. This regulation of TTLL4 activity involves its phosphorylation at Y815 and S1136 amino acid residues. CONCLUSION: Our results demonstrate, for the first time, the regulation of TTLL activity through phosphorylation, pointing to NEK5 as a potential effector kinase. We also suggest a general control of tubulin polyglutamylation through NEK family members in human cells.
Understanding the function of the tumor microenvironment, and compounds from marine organisms for breast cancer therapy.
Malla RR, Farran B, Nagaraju GP
World J Biol Chem · 2021 Mar · PMID 33815682 · Full text
The pathology and physiology of breast cancer (BC), including metastasis, and drug resistance, is driven by multiple signaling pathways in the tumor microenvironment (TME), which hamper antitumor immunity. Recently, long...
The pathology and physiology of breast cancer (BC), including metastasis, and drug resistance, is driven by multiple signaling pathways in the tumor microenvironment (TME), which hamper antitumor immunity. Recently, long non-coding RNAs have been reported to mediate pathophysiological develop-ments such as metastasis as well as immune suppression within the TME. Given the complex biology of BC, novel personalized therapeutic strategies that address its diverse pathophysiologies are needed to improve clinical outcomes. In this review, we describe the advances in the biology of breast neoplasia, including cellular and molecular biology, heterogeneity, and TME. We review the role of novel molecules such as long non-coding RNAs in the pathophysiology of BC. Finally, we provide an up-to-date overview of anticancer compounds extracted from marine microorganisms, crustaceans, and fishes and their synergistic effects in combination with other anticancer drugs. Marine compounds are a new discipline of research in BC and offer a wide range of anti-cancer effects that could be harnessed to target the various pathways involved in BC development, thus assisting current therapeutic regimens.
Inhibition of matrix metalloproteinase-9 secretion by dimethyl sulfoxide and cyclic adenosine monophosphate in human monocytes.
Denner DR, Udan-Johns ML, Nichols MR
World J Biol Chem · 2021 Jan · PMID 33552397 · Full text
BACKGROUND: Matrix metalloproteinases (MMPs), including MMP-9, are an integral part of the immune response and are upregulated in response to a variety of stimuli. New details continue to emerge concerning the mechanisti...
BACKGROUND: Matrix metalloproteinases (MMPs), including MMP-9, are an integral part of the immune response and are upregulated in response to a variety of stimuli. New details continue to emerge concerning the mechanistic and regulatory pathways that mediate MMP-9 secretion. There is significant evidence for regulation of inflammation by dimethyl sulfoxide (DMSO) and 3',5'-cyclic adenosine monophosphate (cAMP), thus investigation of how these two molecules may regulate both MMP-9 and tumor necrosis factor α (TNFα) secretion by human monocytes was of high interest. The hypothesis tested in this study was that DMSO and cAMP regulate MMP-9 and TNFα secretion by distinct mechanisms. AIM: To investigate the regulation of lipopolysaccharide (LPS)-stimulated MMP-9 and tumor necrosis factor α secretion in THP-1 human monocytes by dimethyl sulfoxide and cAMP. METHODS: The paper describes a basic research study using THP-1 human monocyte cells. All experiments were conducted at the University of Missouri-St. Louis in the Department of Chemistry and Biochemistry. Human monocyte cells were grown, cultured, and prepared for experiments in the University of Missouri-St. Louis Cell Culture Facility as per accepted guidelines. Cells were treated with LPS for selected exposure times and the conditioned medium was collected for analysis of MMP-9 and TNFα production. Inhibitors including DMSO, cAMP regulators, and anti-TNFα antibody were added to the cells prior to LPS treatment. MMP-9 secretion was analyzed by gel electrophoresis/western blot and quantitated by ImageJ software. TNFα secretion was analyzed by enzyme-linked immuno sorbent assay. All data is presented as the average and standard error for at least 3 trials. Statistical analysis was done using a two-tailed paired Student -test. values less than 0.05 were considered significant and designated as such in the Figures. LPS and cAMP regulators were from Sigma-Aldrich, MMP-9 standard and antibody and TNFα antibodies were from R&D Systems, and amyloid-β peptide was from rPeptide. RESULTS: In our investigation of MMP-9 secretion from THP-1 human monocytes, we made the following findings. Inclusion of DMSO in the cell treatment inhibited LPS-induced MMP-9, but not TNFα, secretion. Inclusion of DMSO in the cell treatment at different concentrations inhibited LPS-induced MMP-9 secretion in a dose-dependent fashion. A cell-permeable cAMP analog, dibutyryl cAMP, inhibited both LPS-induced MMP-9 and TNFα secretion. Pretreatment of the cells with the adenylyl cyclase activator forskolin inhibited LPS-induced MMP-9 and TNFα secretion. Pretreatment of the cells with the general cAMP phosphodiesterase inhibitor IBMX reduced LPS-induced MMP-9 and TNFα in a dose-dependent fashion. Pre-treatment of monocytes with an anti-TNFα antibody blocked LPS-induced MMP-9 and TNFα secretion. Amyloid-β peptide induced MMP-9 secretion, which occurred much later than TNFα secretion. The latter two findings strongly suggested an upstream role for TNFα in mediating LPS-stimulate MMP-9 secretion. CONCLUSION: The cumulative data indicated that MMP-9 secretion was a distinct process from TNFα secretion and occurred downstream. First, DMSO inhibited MMP-9, but not TNFα, suggesting that the MMP-9 secretion process was selectively altered. Second, cAMP inhibited both MMP-9 and TNFα with a similar potency, but at different monocyte cell exposure time points. The pattern of cAMP inhibition for these two molecules suggested that MMP-9 secretion lies downstream of TNFα and that TNFα may a key component of the pathway leading to MMP-9 secretion. This temporal relationship fit a model whereby early TNFα secretion directly led to later MMP-9 secretion. Lastly, antibody-blocking of TNFα diminished MMP-9 secretion, suggesting a direct link between TNFα secretion and MMP-9 secretion.
Prevalence, serotyping and drug susceptibility patterns of isolates from kidney transplanted patients with urinary tract infections.
Khah AN, Hakemi-Vala M, Samavat S … +1 more , Nasiri MJ
World J Biol Chem · 2020 Nov · PMID 33274016 · Full text
BACKGROUND: Extended-spectrum β-lactamase (ESBL)-producing () are among the main pathogens in urinary tract infections (UTIs) among kidney transplant patients (KTPs). AIM: To estimate the prevalence of ESBL-producing i...
BACKGROUND: Extended-spectrum β-lactamase (ESBL)-producing () are among the main pathogens in urinary tract infections (UTIs) among kidney transplant patients (KTPs). AIM: To estimate the prevalence of ESBL-producing in KTPs and to evaluate the most prevalent serotypes and antibacterial susceptibility patterns of isolated bacteria in Tehran, Iran. METHODS: A total of 60 clinical isolates of uropathogenic were collected from 3 kidney transplant centers from April to May 2019. Antimicrobial susceptibility testing was performed by the disk diffusion method as recommended by the Clinical Laboratory and Standards Institute. The serotyping of isolates was performed by the slide agglutination method. The presence of , and genes was evaluated by polymerase chain reaction. RESULTS: The frequency of ESBL-producing in KTPs was found to be 33.4%. All of the 60 isolates were found to be susceptible to doripenem (100%) and ertapenem (100%). High resistance rates to ampicillin (86%), cefotaxime (80%), and cefazolin (77%) were also documented. The most frequent serotypes were serotype I (50%), serotype II (15%), serotype III (25%), and serotype VI (10%). The gene most frequently found was (55%), followed by (51%) and (41%). CONCLUSION: Molecular analysis showed that was the most common ESBL-encoding gene. The high resistance to β-lactams antibiotics (, ampicillin, cefotaxime, and cefazolin) found in from KTPs with UTIs remains a serious clinical challenge. Further efforts to control ESBL-producing should include the careful use of all antibiotics as well as barrier precautions to reduce spread.
Deciphering the modifiers for phenotypic variability of X-linked adrenoleukodystrophy.
Palakuzhiyil SV, Christopher R, Chandra SR
World J Biol Chem · 2020 Nov · PMID 33274015 · Full text
X-linked adrenoleukodystrophy (X-ALD), an inborn error of peroxisomal β-oxidation, is caused by defects in the ATP Binding Cassette Subfamily D Member 1 () gene. X-ALD patients may be asymptomatic or present with several...
X-linked adrenoleukodystrophy (X-ALD), an inborn error of peroxisomal β-oxidation, is caused by defects in the ATP Binding Cassette Subfamily D Member 1 () gene. X-ALD patients may be asymptomatic or present with several clinical phenotypes varying from severe to mild, severe cerebral adrenoleuko-dystrophy to mild adrenomyeloneuropathy (AMN). Although most female heterozygotes present with AMN-like symptoms after 60 years of age, occasional cases of females with the cerebral form have been reported. Phenotypic variability has been described within the same kindreds and even among monozygotic twins. There is no association between the nature of 1 mutation and the clinical phenotypes, and the molecular basis of phenotypic variability in X-ALD is yet to be resolved. Various genetic, epigenetic, and environmental influences are speculated to modify the disease onset and severity. In this review, we summarize the observations made in various studies investigating the potential modifying factors regulating the clinical manifestation of X-ALD, which could help understand the pathogenesis of the disease and develop suitable therapeutic strategies.
Current understanding of glucose transporter 4 expression and functional mechanisms.
Wang T, Wang J, Hu X … +2 more , Huang XJ, Chen GX
World J Biol Chem · 2020 Nov · PMID 33274014 · Full text
Glucose is used aerobically and anaerobically to generate energy for cells. Glucose transporters (GLUTs) are transmembrane proteins that transport glucose across the cell membrane. Insulin promotes glucose utilization in...
Glucose is used aerobically and anaerobically to generate energy for cells. Glucose transporters (GLUTs) are transmembrane proteins that transport glucose across the cell membrane. Insulin promotes glucose utilization in part through promoting glucose entry into the skeletal and adipose tissues. This has been thought to be achieved through insulin-induced GLUT4 translocation from intracellular compartments to the cell membrane, which increases the overall rate of glucose flux into a cell. The insulin-induced GLUT4 translocation has been investigated extensively. Recently, significant progress has been made in our understanding of GLUT4 expression and translocation. Here, we summarized the methods and reagents used to determine the expression levels of mRNA and GLUT4 protein, and GLUT4 translocation in the skeletal muscle, adipose tissues, heart and brain. Overall, a variety of methods such real-time polymerase chain reaction, immunohistochemistry, fluorescence microscopy, fusion proteins, stable cell line and transgenic animals have been used to answer particular questions related to GLUT4 system and insulin action. It seems that insulin-induced GLUT4 translocation can be observed in the heart and brain in addition to the skeletal muscle and adipocytes. Hormones other than insulin can induce GLUT4 translocation. Clearly, more studies of GLUT4 are warranted in the future to advance of our understanding of glucose homeostasis.
Epigenetic basis of Alzheimer disease.
Tecalco-Cruz AC, Ramírez-Jarquín JO, Alvarez-Sánchez ME … +1 more , Zepeda-Cervantes J
World J Biol Chem · 2020 Sep · PMID 33024518 · Full text
Alzheimer disease (AD) is the primary form of dementia that occurs spontaneously in older adults. Interestingly, the epigenetic profile of the cells forming the central nervous system changes during aging and may contrib...
Alzheimer disease (AD) is the primary form of dementia that occurs spontaneously in older adults. Interestingly, the epigenetic profile of the cells forming the central nervous system changes during aging and may contribute to the progression of some neurodegenerative diseases such as AD. In this review, we present general insights into relevant epigenetic mechanisms and their relationship with aging and AD. The data suggest that some epigenetic changes during aging could be utilized as biomarkers and target molecules for the prevention and control of AD.
Regulation of cytochrome c oxidase contributes to health and optimal life.
Kadenbach B
World J Biol Chem · 2020 Sep · PMID 33024517 · Full text
The generation of cellular energy in the form of ATP occurs mainly in mitochondria by oxidative phosphorylation. Cytochrome c oxidase (CytOx), the oxygen accepting and rate-limiting step of the respiratory chain, regulat...
The generation of cellular energy in the form of ATP occurs mainly in mitochondria by oxidative phosphorylation. Cytochrome c oxidase (CytOx), the oxygen accepting and rate-limiting step of the respiratory chain, regulates the supply of variable ATP demands in cells by "allosteric ATP-inhibition of CytOx." This mechanism is based on inhibition of oxygen uptake of CytOx at high ATP/ADP ratios and low ferrocytochrome c concentrations in the mitochondrial matrix cooperative interaction of the two substrate binding sites in dimeric CytOx. The mechanism keeps mitochondrial membrane potential ΔΨ and reactive oxygen species (ROS) formation at low healthy values. Stress signals increase cytosolic calcium leading to Ca-dependent dephosphorylation of CytOx subunit I at the cytosolic side accompanied by switching off the allosteric ATP-inhibition and monomerization of CytOx. This is followed by increase of ΔΨ and formation of ROS. A hypothesis is presented suggesting a dynamic change of binding of NDUFA4, originally identified as a subunit of complex I, between monomeric CytOx (active state with high ΔΨ, high ROS and low efficiency) and complex I (resting state with low ΔΨ, low ROS and high efficiency).
Targeting the phosphoinositide-3-kinase/protein kinase B pathway in airway innate immunity.
Gopallawa I, Lee RJ
World J Biol Chem · 2020 Sep · PMID 33024516 · Full text
The airway innate immune system maintains the first line of defense against respiratory infections. The airway epithelium and associated immune cells protect the respiratory system from inhaled foreign organisms. These c...
The airway innate immune system maintains the first line of defense against respiratory infections. The airway epithelium and associated immune cells protect the respiratory system from inhaled foreign organisms. These cells sense pathogens activation of receptors like toll-like receptors and taste family 2 receptors (T2Rs) and respond by producing antimicrobials, inflammatory cytokines, and chemokines. Coordinated regulation of fluid secretion and ciliary beating facilitates clearance of pathogens mucociliary transport. Airway cells also secrete antimicrobial peptides and radicals to directly kill microorganisms and inactivate viruses. The phosphoinositide-3-kinase/protein kinase B (Akt) kinase pathway regulates multiple cellular targets that modulate cell survival and proliferation. Akt also regulates proteins involved in innate immune pathways. Akt phosphorylates endothelial nitric oxide synthase (eNOS) enzymes expressed in airway epithelial cells. Activation of eNOS can have anti-inflammatory, anti-bacterial, and anti-viral roles. Moreover, Akt can increase the activity of the transcription factor nuclear factor erythroid 2 related factor-2 that protects cells from oxidative stress and may limit inflammation. In this review, we summarize the recent findings of non-cancerous functions of Akt signaling in airway innate host defense mechanisms, including an overview of several known downstream targets of Akt involved in innate immunity.
Immunological aspects of COVID-19: What do we know?
Velikova TV, Kotsev SV, Georgiev DS … +1 more , Batselova HM
World J Biol Chem · 2020 Sep · PMID 33024515 · Full text
The newly emerged coronavirus (severe acute respiratory syndrome coronavirus 2 SARS-CoV-2) and the disease that it causes coronavirus disease 2019 (COVID-19) have changed the world we know. Yet, the origin and evolution...
The newly emerged coronavirus (severe acute respiratory syndrome coronavirus 2 SARS-CoV-2) and the disease that it causes coronavirus disease 2019 (COVID-19) have changed the world we know. Yet, the origin and evolution of SARS-CoV-2 remain mostly vague. Many virulence factors and immune mechanisms contribute to the deteriorating effects on the organism during SARS-CoV-2 infection. Both humoral and cellular immune responses are involved in the pathophysiology of the disease, where the principal and effective immune response towards viral infection is the cell-mediated immunity. The clinical picture of COVID-19, which includes immune memory and reinfection, remains unclear and unpredictable. However, many hopes are put in developing an effective vaccine against the virus, and different therapeutic options have been implemented to find effective, even though not specific, treatment to the disease. We can assume that the interaction between the SARS-CoV-2 virus and the individual's immune system determines the onset and development of the disease significantly.
Why the discovery of adherent-invasive molecular markers is so challenging?
Camprubí-Font C, Martinez-Medina M
World J Biol Chem · 2020 Apr · PMID 32405343 · Full text
Adherent-invasive (AIEC) strains have been extensively related to Crohn's disease (CD) etiopathogenesis. Higher AIEC prevalence in CD patients versus controls has been reported, and its mechanisms of pathogenicity have...
Adherent-invasive (AIEC) strains have been extensively related to Crohn's disease (CD) etiopathogenesis. Higher AIEC prevalence in CD patients versus controls has been reported, and its mechanisms of pathogenicity have been linked to CD physiopathology. In CD, the therapeutic armamentarium remains limited and non-curative; hence, the necessity to better understand AIEC as a putative instigator or propagator of the disease is certain. Nonetheless, AIEC identification is currently challenging because it relies on phenotypic assays based on infected cell cultures which are highly time-consuming, laborious and non-standardizable. To address this issue, AIEC molecular mechanisms and virulence genes have been studied; however, a specific and widely distributed genetic AIEC marker is still missing. The finding of molecular tools to easily identify AIEC could be useful in the identification of AIEC carriers who could profit from personalized treatment. Also, it would significantly promote AIEC epidemiological studies. Here, we reviewed the existing data regarding AIEC genetics and presented those molecular markers that could assist with AIEC identification. Finally, we highlighted the problems behind the discovery of exclusive AIEC biomarkers and proposed strategies to facilitate the search of AIEC signature sequences.
Complex interactomes and post-translational modifications of the regulatory proteins HABP4 and SERBP1 suggest pleiotropic cellular functions.
Colleti C, Melo-Hanchuk TD, da Silva FRM … +2 more , Saito Â, Kobarg J
World J Biol Chem · 2019 Nov · PMID 31768228 · Full text
The 57 kDa antigen recognized by the Ki-1 antibody, is also known as intracellular hyaluronic acid binding protein 4 and shares 40.7% identity and 67.4% similarity with serpin mRNA binding protein 1, which is also named...
The 57 kDa antigen recognized by the Ki-1 antibody, is also known as intracellular hyaluronic acid binding protein 4 and shares 40.7% identity and 67.4% similarity with serpin mRNA binding protein 1, which is also named CGI-55, or plasminogen activator inhibitor type-1-RNA binding protein-1, indicating that they might be paralog proteins, possibly with similar or redundant functions in human cells. Through the identification of their protein interactomes, both regulatory proteins have been functionally implicated in transcriptional regulation, mRNA metabolism, specifically RNA splicing, the regulation of mRNA stability, especially, in the context of the progesterone hormone response, and the DNA damage response. Both proteins also show a complex pattern of post-translational modifications, involving Ser/Thr phosphorylation, mainly through protein kinase C, arginine methylation and SUMOylation, suggesting that their functions and locations are highly regulated. Furthermore, they show a highly dynamic cellular localization pattern with localizations in both the cytoplasm and nucleus as well as punctuated localizations in both granular cytoplasmic protein bodies, upon stress, and nuclear splicing speckles. Several reports in the literature show altered expressions of both regulatory proteins in a series of cancers as well as mutations in their genes that may contribute to tumorigenesis. This review highlights important aspects of the structure, interactome, post-translational modifications, sub-cellular localization and function of both regulatory proteins and further discusses their possible functions and their potential as tumor markers in different cancer settings.
Fasciculation and elongation zeta proteins 1 and 2: From structural flexibility to functional diversity.
Teixeira MB, Alborghetti MR, Kobarg J
World J Biol Chem · 2019 Feb · PMID 30815230 · Full text
Fasciculation and elongation zeta/zygin (FEZ) proteins are a family of hub proteins and share many characteristics like high connectivity in interaction networks, they are involved in several cellular processes, evolve s...
Fasciculation and elongation zeta/zygin (FEZ) proteins are a family of hub proteins and share many characteristics like high connectivity in interaction networks, they are involved in several cellular processes, evolve slowly and in general have intrinsically disordered regions. In 1985, gene was firstly described and involved in axonal growth in , and in 1997 Bloom and Horvitz enrolled also the human homologues genes, and , in this process. While nematodes possess one gene (), mammalians have one more copy ( and ). Several animal models have been used to study FEZ family functions like: , and human cells. Complementation assays were performed and demonstrated the function conservation between paralogues. Human FEZ1 protein is more studied followed by UNC-76 and FEZ2 proteins, respectively. While FEZ1 and UNC-76 shared interaction partners, FEZ2 evolved and increased the number of protein-protein interactions (PPI) with cytoplasmatic partners. FEZ proteins are implicated in intracellular transport, acting as bivalent cargo transport adaptors in kinesin-mediated movement. Especially in light of this cellular function, this family of proteins has been involved in several processes like neuronal development, neurological disorders, viral infection and autophagy. However, nuclear functions of FEZ proteins have been explored as well, due to high content of PPI with nuclear proteins, correlating FEZ1 expression to and gene regulation and retinoic acid signaling. These recent findings open new avenue to study FEZ proteins functions and its involvement in already described processes. This review intends to reunite aspects of evolution, structure, interaction partners and function of FEZ proteins and correlate them to physiological and pathological processes.
Last decade update for three-finger toxins: Newly emerging structures and biological activities.
Utkin YN
World J Biol Chem · 2019 Jan · PMID 30622682 · Full text
Three-finger toxins (TFTs) comprise one of largest families of snake venom toxins. While they are principal to and the most toxic components of the venoms of the snake family, their presence has also been detected in th...
Three-finger toxins (TFTs) comprise one of largest families of snake venom toxins. While they are principal to and the most toxic components of the venoms of the snake family, their presence has also been detected in the venoms of snakes from other families. The first TFT, α-bungarotoxin, was discovered almost 50 years ago and has since been used widely as a specific marker of the α7 and muscle-type nicotinic acetylcholine receptors. To date, the number of TFT amino acid sequences deposited in the UniProt Knowledgebase free-access database is more than 700, and new members are being added constantly. Although structural variations among the TFTs are not numerous, several new structures have been discovered recently; these include the disulfide-bound dimers of TFTs and toxins with nonstandard pairing of disulfide bonds. New types of biological activities have also been demonstrated for the well-known TFTs, and research on this topic has become a hot topic of TFT studies. The classic TFTs α-bungarotoxin and α-cobratoxin, for example, have now been shown to inhibit ionotropic receptors of γ-aminobutyric acid, and some muscarinic toxins have been shown to interact with adrenoceptors. New, unexpected activities have been demonstrated for some TFTs as well, such as toxin interaction with interleukin or insulin receptors and even TFT-activated motility of sperm. This minireview provides a summarization of the data that has emerged in the last decade on the TFTs and their activities.
Autism and carnitine: A possible link.
Demarquoy C, Demarquoy J
World J Biol Chem · 2019 Jan · PMID 30622681 · Full text
Patients with autism spectrum disorders (ASD) present deficits in social interactions and communication, they also show limited and stereotypical patterns of behaviors and interests. The pathophysiological bases of ASD h...
Patients with autism spectrum disorders (ASD) present deficits in social interactions and communication, they also show limited and stereotypical patterns of behaviors and interests. The pathophysiological bases of ASD have not been defined yet. Many factors seem to be involved in the onset of this disorder. These include genetic and environmental factors, but autism is not linked to a single origin, only. Autism onset can be connected with various factors such as metabolic disorders: including carnitine deficiency. Carnitine is a derivative of two amino acid lysine and methionine. Carnitine is a cofactor for a large family of enzymes: the carnitine acyltransferases. Through their action these enzymes (and L-carnitine) are involved in energy production and metabolic homeostasis. Some people with autism (less than 20%) seem to have L-carnitine metabolism disorders and for these patients, a dietary supplementation with L-carnitine is beneficial. This review summarizes the available information on this topic.
About
- Frequency
- Sun
- Papers found
- 200
- RSS feed
- Subscribe