Journal of physiology and biochemistry最新文献

{"title":"Soluble alpha-klotho and 25-hydroxivitamin D are not associated with brown adipose tissue metabolism in young healthy adults.","authors":"Francisco J Amaro-Gahete, Héctor Vázquez-Lorente, Guillermo Sanchez-Delgado, Jonatan R Ruiz","doi":"10.1007/s13105-025-01072-z","DOIUrl":"https://doi.org/10.1007/s13105-025-01072-z","url":null,"abstract":"<p><strong>Background: </strong>Soluble Alpha-Klotho (S-αklotho) protein and 25-Hydroxyvitamin D (25-OH-D) have emerged as potential modulators for activating and recruiting Brown Adipose Tissue (BAT). The present study aimed to investigate whether circulating S-αklotho and 25-OH-D levels are related to BAT volume, ¹⁸Fluorine-Fluorodeoxyglucose (¹⁸F-FDG) uptake, and BAT radiodensity in young healthy adults.</p><p><strong>Methods: </strong>A total of 128 participants (68% women) aged 18-25 years old participated in this cross-sectional study. Serum levels of S-αklotho were determined by a solid-phase sandwich enzyme-linked immunosorbent assay kit and 25-OH-D serum levels were analyzed using a competitive chemiluminescence immunoassay, both in blood samples collected after an overnight fast. All participants underwent a personalized cold exposure to determine their BAT volume, ¹⁸F-FDG uptake, and radiodensity, using a static positron emission tomography combined with computed tomography scan.</p><p><strong>Results: </strong>After adjusting for multiple covariates, serum levels of S-αklotho (all R² ≤ 0.228 and P ≥ 0.364), 25-OH-D as continuous (all R² ≤ 0.242 and P ≥ 0.088) or by vitamin D status (all R² ≤ 0.767 and P ≥ 0.061) were not associated with either BAT volume and ¹⁸F-FDG uptake, or BAT radiodensity.</p><p><strong>Conclusion: </strong>Serum S-αklotho and 25-OH-D levels within the physiological range are not related to BAT-related variables in young healthy adults. Further studies are needed to fully understand the underlying mechanisms involved in BAT metabolism in humans. (ACTIBATE; ClinicalTrials.gov identifier: not applicable).</p>","PeriodicalId":16779,"journal":{"name":"Journal of physiology and biochemistry","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143597244","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Candidate gene polymorphisms and power athlete status: a meta-analytical approach.","authors":"Gökhan İpekoğlu, Tuğba Çetin, Tülay Sırtbaş, Rabia Kılıç, Mustafa Odabaşı, Fahrettin Bayraktar","doi":"10.1007/s13105-025-01071-0","DOIUrl":"https://doi.org/10.1007/s13105-025-01071-0","url":null,"abstract":"<p><p>Recent studies have focused on genetic polymorphisms that may influence athlete status. This meta-analysis aimed to investigate the association between athlete status and specific candidate genetic polymorphisms (AGTR2 rs11091046, FTO rs9939609, GALNTL6 rs558129, GNB3 rs5443, MCT1 rs1049434, NOS3 rs2070744). Only case-control studies collected from PubMed and Web of Science databases, published between 2009 and 2022, were included. A total of 23 studies were included in the meta-analysis according to the criteria of the research, and analyses were performed using random or fixed effects models. Effect size, odds ratio, or risk ratio were evaluated with a suitable 95% confidence interval. The results showed that the GALNTL6 rs558129 T/T genotype, MCT1 rs1049434 T/T genotype, and NOS3 rs2070744 T allele and T/T genotype were more prevalent in power athletes than in controls (p < 0.05). Conversely, the GALNTL6 rs558129 C allele, C/C genotype, and AGTR2 rs11091046 C allele and C/C genotype were more common in the control group. These findings indicate that some genetic polymorphisms may be important markers in athlete status and should be supported by future studies.</p>","PeriodicalId":16779,"journal":{"name":"Journal of physiology and biochemistry","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143586115","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The impact of high altitude (hypobaric hypoxia) on insulin resistance in humans.","authors":"María M Adeva-Andany, Lucia Adeva-Contreras, Natalia Carneiro-Freire, Eva Ameneiros-Rodríguez, Matilde Vila-Altesor, Isabel Calvo-Castro","doi":"10.1007/s13105-025-01069-8","DOIUrl":"https://doi.org/10.1007/s13105-025-01069-8","url":null,"abstract":"<p><p>Exposure to hypobaric hypoxia (high altitude) diminishes systemic tissue oxygenation. Tissue hypoxia induces insulin resistance and a metabolic switch that reduces oxidative phosphorylation and glucose storage while enhancing glycolysis. Similarly to hypobaric hypoxia, insulin resistance develops in normal humans undergoing normobaric hypoxia and in patients with obstructive sleep apnea. Following acute exposure to high altitude, insulin resistance returns to baseline values upon returning to sea level or when compensatory mechanisms restore tissue oxygenation. However, insulin resistance persists in subjects unable to achieve sufficient oxygen delivery to tissues. Likewise, long-term residents at high altitude develop persistent insulin resistance when compensatory mechanisms do not attain adequate tissue oxygenation. Among these subjects, insulin resistance may cause clinical complications, such as hypertriglyceridemia, reduced HDL-c, visceral obesity, metabolic dysfunction-associated steatotic liver disease, essential hypertension, type 2 diabetes, subclinical vascular injury, cardiovascular disease, and kidney disease. Impaired tissue oxygenation allows the stabilization of hypoxia-inducible factor-1 (HIF-1), a transcription factor that modulates the transcriptional activity of a number of genes to coordinate the physiological responses to tissue hypoxia. Among them, HIF-1 downregulates PPARG, that codes peroxisome proliferator-activated receptor-gamma (PPAR-γ) and PPARGCA, that codes PPAR-γ coactivator-1α, in order to enable insulin resistance and the metabolic switch from oxidative phosphorylation toward glycolysis.</p>","PeriodicalId":16779,"journal":{"name":"Journal of physiology and biochemistry","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143523715","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Matrix stiffening induces hepatocyte functional impairment and DNA damage via the Piezo1‒ERK1/2 signaling pathway.","authors":"Yanan Fan, Caizhelin An, Zhihui Wang, Jia Luo, Wenbin Wang, Qing Luo, Guanbin Song","doi":"10.1007/s13105-025-01070-1","DOIUrl":"https://doi.org/10.1007/s13105-025-01070-1","url":null,"abstract":"<p><p>Hepatocytes are the primary functional cells in the liver, and the malignant transformation of hepatocytes significantly contributes to hepatocellular carcinoma (HCC) progression. Liver fibrosis and cirrhosis caused by extracellular matrix (ECM) remodeling during liver lesions is a pivotal driver of HCC. However, the impact of matrix stiffness on hepatocytes and the underlying molecular mechanisms are not fully understood. Herein, using gelatin/sodium alginate hydrogels with different stiffnesses to simulate the change of matrix stiffness during liver lesions, we found that matrix stiffening leads to a notable decrease in the expression of hepatocyte nuclear factor 4α (HNF4α) and functional hepatocyte genes and a significant increase in the expression of interleukin 6 (IL‒6) in human hepatocyte line L‒02 cells, indicating obvious damage of hepatocyte function. In addition, matrix stiffening causes extensive DNA damage to L‒02 cells. Mechanistically, matrix stiffening upregulates piezo‒type mechanosensitive ion channel component 1 (Piezo1) expression and activates extracellular signal‒regulated kinase 1/2 (ERK1/2) signaling. Piezo1 knockdown suppresses matrix stiffening‒induced functional impairment and DNA damage in L‒02 cells. Moreover, Piezo1 knockdown blocks matrix stiffening‒activated ERK1/2 signaling in L‒02 cells. U0126 (a selective inhibitor of ERK1/2 activation) treatment could rescue matrix stiffening‒induced functional impairment and DNA damage. Taken together, these findings demonstrate that matrix stiffening induces functional impairment and DNA damage in L‒02 cells via the Piezo1‒ERK1/2 signaling pathway, which provides evidence for a better understanding of the hepatocyte function damage caused by tissue mechanical microenvironment change in liver diseases and the mechanotransduction in this process.</p>","PeriodicalId":16779,"journal":{"name":"Journal of physiology and biochemistry","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143492503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The link between Mitochondria and Sarcopenia.","authors":"Nurul Tihani Kamarulzaman, Suzana Makpol","doi":"10.1007/s13105-024-01062-7","DOIUrl":"https://doi.org/10.1007/s13105-024-01062-7","url":null,"abstract":"<p><p>Sarcopenia, a widespread condition, is characterized by a variety of factors influencing its development. The causes of sarcopenia differ depending on the age of the individual. It is defined as the combination of decreased muscle mass and impaired muscle function, primarily observed in association with ageing. As people age from 20 to 80 years old, there is an approximate 30% reduction in muscle mass and a 20% decline in cross-sectional area. This decline is attributed to a decrease in the size and number of muscle fibres. The regression of muscle mass and strength increases the risk of fractures, frailty, reduced quality of life, and loss of independence. Muscle cells, fibres, and tissues shrink, resulting in diminished muscle power, volume, and strength in major muscle groups. One prominent theory of cellular ageing posits a strong positive relationship between age and oxidative damage. Heightened oxidative stress leads to early-onset sarcopenia, characterized by neuromuscular innervation breakdown, muscle atrophy, and dysfunctional mitochondrial muscles. Ageing muscles generate more reactive oxygen species (ROS), and experience decreased oxygen consumption and ATP synthesis compared to younger muscles. Additionally, changes in mitochondrial protein interactions, cristae structure, and networks may contribute to ADP insensitivity, which ultimately leads to sarcopenia. Within this framework, this review provides a comprehensive summary of our current understanding of the role of mitochondria in sarcopenia and other muscle degenerative diseases, highlighting the crucial need for further research in these areas.</p>","PeriodicalId":16779,"journal":{"name":"Journal of physiology and biochemistry","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143449338","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modulation of test anxiety-induced salivary protein secretion by ovarian steroid hormones: a preliminary study.","authors":"Lorenzo Zallocco, Maurizio Ronci, Andrea Pantalone, Maria Rosa Mazzoni, Eleonora Ramoretti, Antonio Lucacchini, Laura Giusti, Laura Sebastiani","doi":"10.1007/s13105-025-01067-w","DOIUrl":"https://doi.org/10.1007/s13105-025-01067-w","url":null,"abstract":"<p><p>In women the menstrual cycle influences mood and anxiety. Aim of this study was to preliminarily investigate whether different ovarian steroid hormone levels may modulate the psychophysiological responses elicited by test anxiety. Specifically, we compared the secretion of anxiety-induced salivary proteins of healthy women in the early follicular (Pre-Ov group) (low ovarian steroid hormones levels) and mid-luteal (Post-Ov group) (medium/high ovarian steroid hormones levels) phase of the menstrual cycle, during the simulation of an oral examination. Saliva samples were collected before and after a relaxation period and at two post-simulation times and analyzed by two-dimensional electrophoresis and western blot. Proteins corresponding to spots differentially expressed in the two groups across the session were identified through mass spectrometry and most of them corresponded to acute stress and/or oral mucosa immunity biomarkers. The task induced an increase in alpha-amylase, carbonic anhydrase and cystatin S, and a decrease in immunoglobulin light/J chains in both groups. Analogous changes in these proteins have previously been linked to psychological or physical stress. However, specific spots corresponding, for example, to cystatins and 14-3-3 protein, changed exclusively in the Pre-Ov group, while prolactin-inducible protein, polymeric immunoglobulin receptor, fragments of alpha-amylase and immunoglobulins only in the Post-Ov group, indicating a potential modulation of their secretion by ovarian steroid hormones. Overall, the results provide preliminary evidence that ovarian steroid hormones may be a driving factor for differences in physiological responses induced by test anxiety. The results are promising, but further validation in a larger sample is needed.</p>","PeriodicalId":16779,"journal":{"name":"Journal of physiology and biochemistry","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143370747","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aerobic exercise timing affects mitochondrial dynamics and insulin resistance by regulating the circadian clock protein expression and NAD⁺-SIRT1-PPARα-MFN2 pathway in the skeletal muscle of high-fat-diet-induced diabetes mice.","authors":"Raha Pourabdi, Fereshteh Shahidi, Mohammad Reza Tabandeh, Mojtaba Salehpour","doi":"10.1007/s13105-024-01066-3","DOIUrl":"https://doi.org/10.1007/s13105-024-01066-3","url":null,"abstract":"<p><p>The circadian clock regulates mitochondrial function and affects time-dependent metabolic responses to exercise. The present study aimed to determine the effects of aerobic exercise timing at the light-dark phase on the proteins expression of the circadian clock, mitochondrial dynamics, and, NAD⁺-SIRT1-PPARα axis in skeletal muscle of high-fat diet-induced diabetic mice. In this experimental study, thirty male mice were randomly assigned into two groups based on time: the early light phase, ZT3, and the early dark phase, ZT15, and three groups at each time: (1) Healthy Control (HC), (2) Diabetic Control (DC), and (3) Diabetic + Exercise (DE). Diabetes was induced by 5 weeks of feeding with a high-fat diet and Streptozotocin injection. Following confirmation of diabetes, animals underwent treadmill running at ZT3 and ZT15 for eight-weeks (5 days, 60-80 min, 50-60%Vmax). The expression of proteins of muscle aryl-hydrocarbon receptor nuclear translocator-like-1 (BMAL1), period-2 (PER2), mitofusin-2 (MFN2), dynamin-related proteins-1 (DRP-1), glucose transporter (GLUT4), sirtuin-1 (SIRT1), peroxisome proliferator-activated receptor-alpha (PPARα), and nicotinamide adenine dinucleotide (NAD⁺) level were analyzed in gastrocnemius muscle at both exercise times. The results showed that aerobic exercise at both times reversed the dysregulation of the diabetes-induced skeletal muscle clock by increasing the BMAL1 and PER2 protein levels. Aerobic exercise, especially at ZT15 compared to ZT3, increased GLUT4-mediated glucose uptake, and improved the diabetes-induced imbalance of mitochondrial fusion-fission by a significant increase in MFN2 protein level. Moreover, time-dependent aerobic exercise only at ZT15 increased the SIRT1 and PPARα protein levels and reduced diabetes-induced hyperglycemia. However, the aerobic exercise timing could not restore the attenuation of diabetes-induced NAD⁺ levels and DRP-1 protein. Our findings demonstrated that the synchronization of aerobic exercise with the circadian rhythm of NAD⁺-SIRT1 may boost MFN2-mediated mitochondrial fusion by activating the BMAL1-PER2-SIRT1-PPARα axis in the skeletal muscle of diabetic mice and be more effective in facilitating glycemic control and insulin resistance.</p>","PeriodicalId":16779,"journal":{"name":"Journal of physiology and biochemistry","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142882140","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The emerging role of long non-coding RNA SOX2-OT in cancers and non-malignant diseases.","authors":"Jingjie Yang, Fangshun Tan, Yaohui Chen, Xiaolan Li, Chengfu Yuan","doi":"10.1007/s13105-024-01059-2","DOIUrl":"https://doi.org/10.1007/s13105-024-01059-2","url":null,"abstract":"<p><p>SOX2 overlapping transcript (SOX2-OT) is a long non-coding RNA located at chromosome 3q26.33 in humans. Convincing data confirm that SOX2-OT is evolutionarily conserved and plays a significant role in various malignant and non-malignant diseases. In most cancers, the upregulation of SOX2-OT acts as an oncogenic factor, strongly correlating with tumor risk, adverse clinicopathological features, and poor prognosis. Mechanistically, SOX2-OT is regulated by seven transcription factors and influences cellular behavior by modulating SOX2 expression, competitively binding 20 types of miRNAs, stabilizing protein expression, or promoting protein ubiquitination. It also participates in epigenetic modifications and activates multiple signaling pathways to regulate cancer cell proliferation, apoptosis, migration, invasion, autophagy, immune evasion, and resistance to chemotherapy/targeted therapies. Additionally, SOX2-OT triggers apoptosis, oxidative stress, and inflammatory responses, contributing to neurodevelopmental disorders, cardiovascular diseases, and diabetes-related conditions. Genetic polymorphisms of SOX2-OT have also been linked to breast cancer, gastric cancer, recurrent miscarriage, sepsis, and eating disorders in patients with bipolar disorder. This review provides an overview of recent research progress on SOX2-OT in human diseases, highlights its substantial potential as a prognostic and diagnostic biomarker, and explores its future clinical applications.</p>","PeriodicalId":16779,"journal":{"name":"Journal of physiology and biochemistry","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142864627","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MicroRNA signatures in neuroplasticity, neuroinflammation and neurotransmission in association with depression.","authors":"Anita Choudhary, Anil Kumar, Manav Jindal, M Rhuthuparna, Anjana Munshi","doi":"10.1007/s13105-024-01065-4","DOIUrl":"https://doi.org/10.1007/s13105-024-01065-4","url":null,"abstract":"<p><p>Depression is a multifactorial disorder that occurs mainly on account of the dysregulation of neuroplasticity, neurotransmission and neuroinflammation in the brain. In addition to environmental /lifestyle factors, the pathogenesis of disease has been associated with genetic and epigenetic factors that affect the reprogramming of normal brain function. MicroRNA (miRNAs), a type of non-coding RNAs, are emerging as significant players that play a vital role in the regulation of gene expression and have been extensively explored in neurodegenerative disorders. Recent studies have also shown the role of gut microbiota that forms a complex bidirectional network with gut brain axis, impacting neuroinflammation in case of Parkinson's disease and depression. Translating targeted miRNA-based therapies for the treatment of neurological disorders including depression, into clinical practice remains challenging due to the ineffective delivery of the therapeutic molecules and off-target effects of the specific miRNAs. This review provides significant insights into how miRNAs are emerging as vital players in the development of depression, especially the ones involved in three important processes including neuroplasticity, neurotransmission and neuroinflammation. In this review, the current status of miRNAs as biomarkers for therapeutic interventions in the case of depression has been discussed along with an overview of future perspectives, like use of nanotechnology and gene editing, keeping in view other multifactorial disorders where such interventions by mimics and inhibitors have already reached clinical trials. The challenges for targeting the specific miRNAs for therapeutic outcomes have also been highlighted.</p>","PeriodicalId":16779,"journal":{"name":"Journal of physiology and biochemistry","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142854515","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The mechanism of LQTS related CaM mutation E141G interfering with Ca_V1.2 channels function through its C-lobe.","authors":"Chenyang Zhang, Dongxue Shao, Xi Zheng, Liying Hao","doi":"10.1007/s13105-024-01064-5","DOIUrl":"https://doi.org/10.1007/s13105-024-01064-5","url":null,"abstract":"<p><p>Mutations in the CALM1-3 genes, which encode calmodulin (CaM), have been reported in clinical cases of long QT syndrome (LQTS). Specifically, the CaM mutant E141G (CaM_E141G) in the variant CALM1 gene has been identified as a causative factor in LQTS. This mutation disrupts the normal Ca²⁺-dependent inactivation (CDI) function of Ca_V1.2 channels. However, it is still unclear how CaM_E141G interferes with the regulatory role of wild-type (WT) CaM on Ca_V1.2 channels and leads to abnormal CDI. A CaM molecule contains two lobes with similar structure, the N-lobe and the C-lobe. In this study, a CaM-truncated C-lobe mutant E141G (C-lobe_E141G) was engineered to exclude the impact of the unmutated N-lobe. Our findings revealed that at low Ca²⁺ concentration ([Ca²⁺]), the binding of C-lobe_E141G to the preIQ, IQ and N-terminus (NT) of Ca_V1.2 channels has higher binding capacity (B_max: 0.17, 0.22, 0.13) compared with those of WT C-lobe (B_max: 0.04, 0.14, 0.11) in GST pull-down assay. With an increase in [Ca²⁺], the Ca²⁺-dependency for C-lobe_E141G binding to Ca_V1.2 channels was impaired. Moreover, C-lobe_E141G induced the relative channel activity to 240.58 ± 51.37% at resting [Ca²⁺], but it was unable to diminish the channel activity at high [Ca²⁺] even in the presence of WT N-lobe, which may be responsible for the abnormal CDI of Ca_V1.2 channels affected by the LQTS-related CaM mutation. Our research provides preliminary insights into the mechanism by which the CaM mutation interferes with Ca_V1.2 channels function through its C-lobe.</p>","PeriodicalId":16779,"journal":{"name":"Journal of physiology and biochemistry","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142854520","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}