Biology subjects

Chibalin, A. V.

Publications and source records attributed to Chibalin, A. V..

5 recordsLinked to original sources

bioRxiv2025

Low-load blood flow restriction training and ischemia modulate expression of Na+,K+-ATPase and FXYDs in human skeletal muscle

Anterior cruciate ligament (ACL) rupture leads to muscle deconditioning and downregulation of Na+,K+-ATPase (NKA). Low-load blood flow restriction (LL-BFR) training was shown to improve muscle function after ACL injury, but its effects on NKA are unknown. We analysed expression of NKA and its FXYD regulators in knee muscles from ACL-injured subjects undergoing LL-BFR, low-load training with sham blood flow restriction (LL-Sham), or no training (Control). Additionally, we dissected effects of ischemia components by subjecting cultured human myotubes to glucose deprivation and/or hypoxia. The LL-BFR group had higher vastus lateralis mRNA levels of NKA1, NKA{beta}3, and FXYD5 than the LL-Sham group. In vitro, NKA1, NKA{beta}1, and NKA{beta}3 mRNA and NKA1 and NKA{beta}1 protein levels were downregulated by sustained ischemia and glucose deprivation, but not hypoxia, while FXYD5 protein was upregulated by glucose deprivation. Conversely, intermittent ischemia had no effect on NKA or FXYD expression. In conclusion, our study shows that LL-BFR training induces specific transcriptional adaptations in vastus lateralis after ACL injury, potentially contributing to functional improvements. Moreover, it shows that glucose availability plays a major role in modulating NKA and FXYD expression in muscle cells under ischemic conditions. NEW & NOTEWORTHYO_LIThis is the first study exploring effects of low-load BFR training on Na+,K+-ATPase (NKA) and FXYD expression in knee muscles after anterior cruciate ligament injury. C_LIO_LIEffects of ischemia components were analysed by subjecting cultured human myotubes to glucose deprivation and/or hypoxia. C_LIO_LILL-BFR training induces specific transcriptional adaptations in vastus lateralis after ACL injury, potentially contributing to functional improvements. C_LIO_LIGlucose plays a major role in modulating NKA and FXYD expression in cultured myotubes under ischemic conditions. C_LI

physiology↗

bioRxiv2025

PDK1: one abbreviation, two kinases, relentless confusion

Despite peer review, hundreds of biomedical articles contain errors due to identical abbreviations that refer to different proteins. This includes PDK1, denoting both pyruvate dehydrogenase kinase 1 and 3-phosphoinositide-dependent protein kinase 1. Our analysis shows that one-out-of-five articles with the term PDK1 on PubMed, published in 2019-2026, state incorrect antibodies, refer to incorrect sequences for PCR, gene silencing, or plasmids, merge the properties of the two proteins, or incorrectly cite the other protein. Confusion extends to websites of biotechnology providers, where PDK1 antibodies and recombinant proteins were misattributed. To mitigate PDK1 abbreviation misuse, we recommend using unique protein abbreviations, clear antibody and sequence identification, and implementation of more rigorous peer review processes, supported by our newly developed PDK1-TermTracker citation network visualization and analysis service.

biochemistry↗

bioRxiv2024

Decreased sarcomeric mitochondrial creatine kinase 2 impairs skeletal muscle mitochondrial function independently of insulin action in type 2 diabetes

Plasma creatine levels are associated with risk of type 2 diabetes. Since skeletal muscle is the main disposal site of both creatine and glucose, we investigated the role of intramuscular creatine metabolism in the pathophysiology of insulin resistance in type 2 diabetes. We report in men with type 2 diabetes, plasma creatine levels are increased, while intramuscular phosphocreatine content is reduced. These alterations are coupled to reduced expression of sarcomeric mitochondrial creatine kinase 2 (CKMT2). In C2C12 myotubes, Ckmt2 silencing reduced mitochondrial respiration, membrane potential, and glucose oxidation. Electroporation-mediated overexpression of Ckmt2 in skeletal muscle of high-fat diet-fed male mice increased mitochondrial respiration, independent of creatine availability. Thus, beyond the canonical role of CKMT2 on creatine phosphorylation, we reveal a previously underappreciated role of CKMT2 on mitochondrial homeostasis, independent of insulin action. Collectively, our data provides functional evidence into how CKMT2 mediates mitochondrial dysfunction associated with type 2 diabetes.

physiology↗

bioRxiv2021

Circadian Transcriptomic and Epigenomic Remodeling in Response to Lipid Overload and Human Obesity

Obesity and elevated circulating lipids may impair metabolism by disrupting the molecular circadian clock. We tested the hypothesis that lipid-overload may interact with the circadian clock and alter the rhythmicity of gene expression through epigenomic mechanisms in skeletal muscle. Palmitate reprogrammed the circadian transcriptome in myotubes without altering the rhythmic mRNA expression of core clock genes. Genes with enhanced cycling in response to palmitate were associated with post-translational modification of histones. Cycling of histone 3 lysine 27 acetylation (H3K27ac), a marker of active gene enhancers, was modified by palmitate treatment. Chromatin immunoprecipitation and sequencing confirmed that palmitate exposure altered the cycling of DNA regions associated with H3K27ac. Overlap of mRNA and DNA regions associated with H3K27ac and pharmacological inhibition of histone acetyl transferases revealed novel cycling genes associated with lipid exposure of primary human myotubes. Palmitate exposure disrupts transcriptomic rhythmicity and modifies enhancers through changes in histone H3K27 acetylation in a circadian manner. Thus, histone acetylation is responsive to lipid-overload and redirects the circadian chromatin landscape leading to reprogramming of circadian genes in skeletal muscle.

physiology↗

bioRxiv2020

Branched-Chain Amino Acid Metabolism is Regulated by ERRα and is Further Impaired by Glucose Loading in Type 2 Diabetes

Aims/hypothesisIncreased levels of branched-chain amino acids (BCAAs) are associated with type 2 diabetes pathogenesis. However, most metabolomic studies are limited to an analysis of plasma metabolites under fasting conditions, rather than the dynamic shift in response to a metabolic challenge. Moreover, metabolomic profiles of peripheral tissues involved in glucose homeostasis are scarce and the transcriptomic regulation of genes involved in BCAA catabolism is partially unknown. This study aimed to identify differences in circulating and skeletal muscle BCAA levels in response to an OGTT in individuals with normal glucose tolerance (NGT) or type 2 diabetes. Additionally, transcription factors involved in the regulation of the BCAA gene set were identified. MethodsPlasma and vastus lateralis muscle biopsies were obtained from individuals with NGT or type 2 diabetes before and after an OGTT. Plasma and quadriceps muscles were harvested from skeletal muscle-specific PGC-1 knockout and transgenic mice. BCAA-related metabolites and genes were assessed by LC-MS/MS and RT-PCR, respectively. Small interfering RNA and adenovirus-mediated overexpression techniques were used in primary human skeletal muscle cells to study the role of PGC-1A and ESRRA in the expression of the BCAA gene set. Radiolabeled leucine was used to analyze the impact of ERR knockdown on leucine oxidation. ResultsImpairments in BCAA catabolism in people with type 2 diabetes under fasting conditions were exacerbated after a glucose load. Branched-chain keto acids were reduced 37-56% after an OGTT in the NGT group, whereas no changes were detected in individuals with T2D. These changes were concomitant with a stronger correlation with glucose homeostasis biomarkers and downregulated expression of BCAT2, BCKDH complex subunits and 69% of downstream BCAA-related genes in skeletal muscle. In primary human myotubes overexpressing PGC-1, 61% of the analyzed BCAA genes were upregulated, while 67% were downregulated in the quadriceps of skeletal muscle-specific PGC-1 knockout mice. ESRRA (encoding estrogen-related receptor , ERR) silencing completely abrogated the PGC-1-induced upregulation of BCAA-related genes in primary human myotubes. Conclusions/interpretationMetabolic inflexibility in type 2 diabetes impacts BCAA homeostasis and attenuates the decrease of circulating and skeletal muscle BCAA-related metabolites after a glucose challenge. Transcriptional regulation of BCAA genes in primary human myotubes via a PGC-1 is ERR-dependent. Research in contextO_ST_ABSWhat is already known about this subject?C_ST_ABSO_LICirculating levels of BCAA are elevated in type 2 diabetes. C_LIO_LIPGC-1 is involved in the transcription of the BCAA gene set. C_LI What is the key question?O_LIDoes metabolic inflexibility associated with type 2 diabetes encompass BCAA homeostasis and PGC-1 mediated transcription of the BCAA gene set? C_LI What are the new findings?O_LIBCAA homeostasis is further compromised by a glucose challenge in type 2 diabetes. C_LIO_LIAn OGTT reveals coordinated regulation between BCAA metabolites, blood glucose, and HbA1c levels. C_LIO_LIERR is essential for PGC-1-mediated BCAA gene expression in primary human myotubes. C_LI How might this impact on clinical practice in the foreseeable future?O_LIAn OGTT can be used to underscore impairments in BCAA metabolism. These findings suggest that interventions targeting the PGC-1/ ERR axis may improve BCAA homeostasis. C_LI

physiology↗