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Pyruvate dehydrogenase kinases: key regulators of cellular metabolism and therapeutic targets for metabolic diseases.
IF 3.7 3区 生物学
Journal of physiology and biochemistry Pub Date : 2025-02-01 Epub Date: 2025-03-21 DOI: 10.1007/s13105-025-01068-9
Min Zhou, Ziqi Qin, Xiting Zhu, Yifeng Ruan, Huiling Ling, Chen Li, Xueqi Gan
{"title":"Pyruvate dehydrogenase kinases: key regulators of cellular metabolism and therapeutic targets for metabolic diseases.","authors":"Min Zhou, Ziqi Qin, Xiting Zhu, Yifeng Ruan, Huiling Ling, Chen Li, Xueqi Gan","doi":"10.1007/s13105-025-01068-9","DOIUrl":"10.1007/s13105-025-01068-9","url":null,"abstract":"<p><p>Pyruvate dehydrogenase kinases (PDKs) can regulate the conversion of pyruvate to acetyl coenzyme A through the mitochondrial pyruvate dehydrogenase complex (PDHC). As the rate-limiting enzymes of PDHC, PDKs link glycolysis to the tricarboxylic acid cycle. Pathological changes in many diseases involve alterations in cellular metabolism, which are partly reflected in changes in mitochondrial function. The intermediate role of PDKs in metabolic processes allows for the influence of both glycolysis and oxidative phosphorylation. Recent studies have shown that PDKs play a crucial role in regulating metabolic reprogramming, mitochondrial function and cellular activities in both oncological studies and various non-oncological diseases. This paper aims to clarify the molecular regulatory mechanisms of PDKs; review the relationship of PDKs with cellular metabolic reprogramming, regulation of ROS, and apoptosis; and the present status of research on PDKs in osteoporosis, diabetes mellitus, and vascular diseases. With this review, we have increased our understanding and insight at the molecular level, providing new insights into targeting PDKs to reverse metabolism-related diseases.</p>","PeriodicalId":16779,"journal":{"name":"Journal of physiology and biochemistry","volume":" ","pages":"21-34"},"PeriodicalIF":3.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143673576","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}
引用次数: 0
Modification of adipogenesis and oxidative stress by quercetin: positive or negative impact on adipose tissue metabolism of obese diabetic Zucker rats? 槲皮素对脂肪生成和氧化应激的改变:对肥胖糖尿病扎克大鼠脂肪组织代谢的积极影响还是消极影响?
IF 3.7 3区 生物学
Journal of physiology and biochemistry Pub Date : 2025-02-01 Epub Date: 2024-11-22 DOI: 10.1007/s13105-024-01060-9
Katarína Kršková, Viktória Dobrócsyová, Kristína Ferenczyová, Jana Hricovíniová, Barbora Kaločayová, Ulrika Duľová, Mahdi Bozorgnia, Monika Barteková, Štefan Zorad
{"title":"Modification of adipogenesis and oxidative stress by quercetin: positive or negative impact on adipose tissue metabolism of obese diabetic Zucker rats?","authors":"Katarína Kršková, Viktória Dobrócsyová, Kristína Ferenczyová, Jana Hricovíniová, Barbora Kaločayová, Ulrika Duľová, Mahdi Bozorgnia, Monika Barteková, Štefan Zorad","doi":"10.1007/s13105-024-01060-9","DOIUrl":"10.1007/s13105-024-01060-9","url":null,"abstract":"<p><p>Reactive oxygen species (ROS) play a key role in the regulation of adipogenesis. The aim of our study was to investigate the effect of quercetin (QCT) supplement on obese adipose tissue metabolism of 30-week-old diabetic Zucker rats (ZDF), not well examined yet. QCT was administered orally at dose of 20 mg/kg body weight/day for 6 weeks. Adipocytes from subcutaneous adipose tissue (ScWAT) were isolated and their size was evaluated by light microscopy. Gene expression of adipogenic markers in subcutaneous and visceral adipose tissue was determined by real-time PCR and expression of proteins involved in lipid and glucose metabolism was determined in ScWAT by immunoblotting. Obese ZDF rats suffered from diabetes, hyperinsulinemia and had higher index HOMA-IR (Homeostatic Model Assessment for Insulin Resistance). Treatment with QCT had no significant impact on these metabolic disorders in genetic model of obesity and type 2 diabetes used in our study. Nevertheless, QCT reduced expression of inflammatory cytokine tumour necrosis factor alpha in ScWAT and also visceral adipose tissue and up-regulated expression of anti-inflammatory adiponectin in ScWAT. A shift in redox equilibrium was detected via inhibition of pro-oxidant genes by QCT. Furthermore, QCT reduced adipocyte size in ScWAT, down-regulated expression of fatty acid synthase and adipogenic markers, and moreover stimulated expression of proteolytic enzymes. These changes likely resulted in reduced fat deposition in ScWAT, which was reflected in the elevated circulated levels of free fatty acids in QCT-treated obese ZDF rats compared with obese untreated controls. This increase could, at least in part, explain why we did not observe an improvement in systemic metabolic health by QCT in our model. In conclusion, our study suggests that preventive treatment with QCT might be more effective than its administration in the stage of fully developed diabetes, and further research in this area is needed.</p>","PeriodicalId":16779,"journal":{"name":"Journal of physiology and biochemistry","volume":" ","pages":"137-156"},"PeriodicalIF":3.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142686733","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}
引用次数: 0
Silenced long non-coding RNA RMST ameliorates cardiac dysfunction and inflammatory response in doxorubicin-induced heart failure in C57BL/6 mice via the modulation of the microRNA-10b-5p/TRAF6 axis. 沉默的长非编码 RNA RMST 可通过调节 microRNA-10b-5p/TRAF6 轴改善多柔比星诱导的 C57BL/6 小鼠心功能不全和炎症反应。
IF 3.7 3区 生物学
Journal of physiology and biochemistry Pub Date : 2025-02-01 Epub Date: 2024-11-22 DOI: 10.1007/s13105-024-01056-5
Heng Cai, Yi Han
{"title":"Silenced long non-coding RNA RMST ameliorates cardiac dysfunction and inflammatory response in doxorubicin-induced heart failure in C57BL/6 mice via the modulation of the microRNA-10b-5p/TRAF6 axis.","authors":"Heng Cai, Yi Han","doi":"10.1007/s13105-024-01056-5","DOIUrl":"10.1007/s13105-024-01056-5","url":null,"abstract":"<p><p>Long non-coding RNA rhabdomyosarcoma 2-associated transcript (RMST) has been found to exert effects on cardiovascular diseases. However, the research for probing its role in heart failure (HF) is limited. Our study intends to unravel the regulatory effects of RMST on HF via the microRNA (miR)-10b-5p/tumor necrosis factor receptor-associated factor 6 (TRAF6) axis. The mouse model of HF was induced by doxorubicin. The expression levels of RMST, miR-10b-5p and TRAF6 were detected. The virus carrying RMST, miR-10b-5p or TRAF6 vectors were injected into doxorubicin-induced HF mice to examine the cardiac function, inflammatory response, pathological changes and cell apoptosis in doxorubicin-induced HF mice. The target relationships among RMST, miR-10b-5p and TRAF6 were confirmed. RMST and TRAF6 were elevated and miR-10b-5p was reduced in doxorubicin-induced HF mice. RMST or TRAF6 silencing or miR-10b-5p overexpression could improve doxorubicin-induced cardiac dysfunction, and inflammatory response, and reduce cardiomyocyte apoptosis. Down-regulation of miR-10b-5p or overexpression of TRAF6 were both able to inverse the therapeutic effect of silencing RMST on doxorubicin-induced HF mice. RMST bound to miR-10b-5p that targeted TRAF6. RMST silencing could attenuate inflammatory response and cardiomyocyte apoptosis and upregulate cardiac function in mice with doxorubicin-induced HF by modulating the miR-10b-5p/TRAF6 axis. The study provides novel therapeutic targets for HF treatment.</p>","PeriodicalId":16779,"journal":{"name":"Journal of physiology and biochemistry","volume":" ","pages":"99-110"},"PeriodicalIF":3.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142686942","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}
引用次数: 0
The emerging role of long non-coding RNA SOX2-OT in cancers and non-malignant diseases. 长链非编码RNA SOX2-OT在癌症和非恶性疾病中的新作用
IF 3.7 3区 生物学
Journal of physiology and biochemistry Pub Date : 2025-02-01 Epub Date: 2024-12-20 DOI: 10.1007/s13105-024-01059-2
Jingjie Yang, Fangshun Tan, Yaohui Chen, Xiaolan Li, Chengfu Yuan
{"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":"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":"57-83"},"PeriodicalIF":3.7,"publicationDate":"2025-02-01","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}
引用次数: 0
The impact of high altitude (hypobaric hypoxia) on insulin resistance in humans.
IF 3.7 3区 生物学
Journal of physiology and biochemistry Pub Date : 2025-02-01 Epub Date: 2025-02-28 DOI: 10.1007/s13105-025-01069-8
María M Adeva-Andany, Lucia Adeva-Contreras, Natalia Carneiro-Freire, Eva Ameneiros-Rodríguez, Matilde Vila-Altesor, Isabel Calvo-Castro
{"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":"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":"35-55"},"PeriodicalIF":3.7,"publicationDate":"2025-02-01","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}
引用次数: 0
Histone demethylase JMJD1C advances macrophage foam cell formation and atherosclerosis progression by promoting the transcription of PCSK9. 组蛋白去甲基化酶 JMJD1C 通过促进 PCSK9 的转录,推动巨噬细胞泡沫细胞的形成和动脉粥样硬化的进展。
IF 3.7 3区 生物学
Journal of physiology and biochemistry Pub Date : 2025-02-01 Epub Date: 2024-11-08 DOI: 10.1007/s13105-024-01058-3
Yiming Wang, Yifei Chen, Jianbo Yang, Wei Sun, Xiaoning Zhang
{"title":"Histone demethylase JMJD1C advances macrophage foam cell formation and atherosclerosis progression by promoting the transcription of PCSK9.","authors":"Yiming Wang, Yifei Chen, Jianbo Yang, Wei Sun, Xiaoning Zhang","doi":"10.1007/s13105-024-01058-3","DOIUrl":"10.1007/s13105-024-01058-3","url":null,"abstract":"<p><p>Macrophage is considered as a critical driving factor in the progression of atherosclerosis (AS), and epigenetic heterogeneity contributes important mechanisms in this process. Here, we identified that a histone demethylase jumonji domain-containing protein 1 C (JMJD1C) is a promising biomarker for atherosclerotic cerebral infarction through clinical analysis. Then, AOPE<sup>-/-</sup> mice fed with a high fat diet and RAW264.7 cells induced by oxidized low-density lipoprotein (ox-LDL) were used as AS models to verify the function of JMJD1C in AS development in vivo and in vitro. JMJD1C knockdown significantly reduced plaque area, inflammation and endothelial damage in AS model mice, and also alleviated foam cell formation, inflammatory cytokines production and cell apoptosis in ox-LDL-treated RAW264.7 cells. Mechanistically, JMJD1C promoted the transcription of proprotein convertase subtilisin/kexin type 9 (PCSK9) through mediating H3 Lysine 9 demethylation. The effects of JMJD1C knockdown on ox-LDL-induced macrophages were blocked by PCSK9 overexpression. Altogether, our study proves that JMJD1C advances macrophage foam cell formation, inflammation and apoptosis to accelerate AS progression through H3 demethylation of PCSK9. The findings underscore the important role of JMJD1C-mediated histone modification in macrophage regulation and AS progression, which brings a new insight into the pathobiology of AS.</p>","PeriodicalId":16779,"journal":{"name":"Journal of physiology and biochemistry","volume":" ","pages":"123-135"},"PeriodicalIF":3.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142603715","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}
引用次数: 0
Prognostic model development using novel genetic signature associated with adenosine metabolism and immune status for patients with hepatocellular carcinoma. 利用与腺苷代谢和免疫状态相关的新型基因特征,为肝细胞癌患者建立预后模型。
IF 3.7 3区 生物学
Journal of physiology and biochemistry Pub Date : 2025-02-01 Epub Date: 2024-11-15 DOI: 10.1007/s13105-024-01061-8
Yidan Chen, Kemei Wang, Xingyun Zhang, Dongying Tao, Yulong Shang, Ping Wang, Qiang Li, Yansheng Liu
{"title":"Prognostic model development using novel genetic signature associated with adenosine metabolism and immune status for patients with hepatocellular carcinoma.","authors":"Yidan Chen, Kemei Wang, Xingyun Zhang, Dongying Tao, Yulong Shang, Ping Wang, Qiang Li, Yansheng Liu","doi":"10.1007/s13105-024-01061-8","DOIUrl":"10.1007/s13105-024-01061-8","url":null,"abstract":"<p><p>The high mortality rate of hepatocellular carcinoma (HCC) is partly due to advanced diagnosis, emphasizing the need for effective predictive tools in HCC treatment. The aim of this study is to propose a novel prognostic model for HCC based on adenosine metabolizing genes and explore the potential relationship between them. Regression analysis was performed to identify differentially expressed genes associated with adenosine metabolism in HCC patients using RNA sequencing data obtained from a public database. Adenosine metabolism-related risk score (AMrisk) was derived using the least absolute shrinkage and selection operator (LASSO) Cox regression and verified using another database. Changes in adenosine metabolism in HCC were analyzed using functional enrichment analysis and multiple immune scores. The gene expression levels in patient samples were validated using quantitative reverse transcription polymerase chain reaction. Thirty adenosine metabolism-related differentially expressed genes were identified in HCC, and six genes (ADA, P2RY4, P2RY6, RPIA, SLC6A3, and VEGFA) were used to calculate the AMrisk score; the higher the risk scores, the lower the overall survival. Moreover, immune infiltration activation and immune checkpoints were considerably higher in the high-risk group. Additional in vitro experiments validated the enhanced expression of these six genes in HCC. The established predictive model demonstrated that adenosine metabolism-related genes was significantly associated with prognosis in HCC patients.</p>","PeriodicalId":16779,"journal":{"name":"Journal of physiology and biochemistry","volume":" ","pages":"157-172"},"PeriodicalIF":3.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142639265","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}
引用次数: 0
Modulation of test anxiety-induced salivary protein secretion by ovarian steroid hormones: a preliminary study.
IF 3.7 3区 生物学
Journal of physiology and biochemistry Pub Date : 2025-02-01 Epub Date: 2025-02-08 DOI: 10.1007/s13105-025-01067-w
Lorenzo Zallocco, Maurizio Ronci, Andrea Pantalone, Maria Rosa Mazzoni, Eleonora Ramoretti, Antonio Lucacchini, Laura Giusti, Laura Sebastiani
{"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":"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":"215-228"},"PeriodicalIF":3.7,"publicationDate":"2025-02-01","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}
引用次数: 0
The mechanism of LQTS related CaM mutation E141G interfering with CaV1.2 channels function through its C-lobe. LQTS相关CaM突变E141G通过c叶干扰CaV1.2通道功能的机制
IF 3.7 3区 生物学
Journal of physiology and biochemistry Pub Date : 2025-02-01 Epub Date: 2024-12-19 DOI: 10.1007/s13105-024-01064-5
Chenyang Zhang, Dongxue Shao, Xi Zheng, Liying Hao
{"title":"The mechanism of LQTS related CaM mutation E141G interfering with Ca<sub>V</sub>1.2 channels function through its C-lobe.","authors":"Chenyang Zhang, Dongxue Shao, Xi Zheng, Liying Hao","doi":"10.1007/s13105-024-01064-5","DOIUrl":"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<sub>E141G</sub>) in the variant CALM1 gene has been identified as a causative factor in LQTS. This mutation disrupts the normal Ca<sup>2+</sup>-dependent inactivation (CDI) function of Ca<sub>V</sub>1.2 channels. However, it is still unclear how CaM<sub>E141G</sub> interferes with the regulatory role of wild-type (WT) CaM on Ca<sub>V</sub>1.2 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<sub>E141G</sub>) was engineered to exclude the impact of the unmutated N-lobe. Our findings revealed that at low Ca<sup>2+</sup> concentration ([Ca<sup>2+</sup>]), the binding of C-lobe<sub>E141G</sub> to the preIQ, IQ and N-terminus (NT) of Ca<sub>V</sub>1.2 channels has higher binding capacity (B<sub>max</sub>: 0.17, 0.22, 0.13) compared with those of WT C-lobe (B<sub>max</sub>: 0.04, 0.14, 0.11) in GST pull-down assay. With an increase in [Ca<sup>2+</sup>], the Ca<sup>2+</sup>-dependency for C-lobe<sub>E141G</sub> binding to Ca<sub>V</sub>1.2 channels was impaired. Moreover, C-lobe<sub>E141G</sub> induced the relative channel activity to 240.58 ± 51.37% at resting [Ca<sup>2+</sup>], but it was unable to diminish the channel activity at high [Ca<sup>2+</sup>] even in the presence of WT N-lobe, which may be responsible for the abnormal CDI of Ca<sub>V</sub>1.2 channels affected by the LQTS-related CaM mutation. Our research provides preliminary insights into the mechanism by which the CaM mutation interferes with Ca<sub>V</sub>1.2 channels function through its C-lobe.</p>","PeriodicalId":16779,"journal":{"name":"Journal of physiology and biochemistry","volume":" ","pages":"185-197"},"PeriodicalIF":3.7,"publicationDate":"2025-02-01","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}
引用次数: 0
Higher plasma levels of endocannabinoids and analogues are correlated with a worse cardiometabolic profile in middle-aged adults. 较高的血浆内源性大麻素和类似物水平与中年人较差的心脏代谢状况相关。
IF 3.7 3区 生物学
Journal of physiology and biochemistry Pub Date : 2025-02-01 Epub Date: 2024-12-05 DOI: 10.1007/s13105-024-01063-6
Carmen Rodríguez-García, Francisco J Osuna-Prieto, Isabelle Kohler, Joaquin Sanchez-Gomez, Samuel Ruiz-Campos, Manuel J Castillo, Francisco J Amaro-Gahete, Borja Martínez-Tellez, Lucas Jurado-Fasoli
{"title":"Higher plasma levels of endocannabinoids and analogues are correlated with a worse cardiometabolic profile in middle-aged adults.","authors":"Carmen Rodríguez-García, Francisco J Osuna-Prieto, Isabelle Kohler, Joaquin Sanchez-Gomez, Samuel Ruiz-Campos, Manuel J Castillo, Francisco J Amaro-Gahete, Borja Martínez-Tellez, Lucas Jurado-Fasoli","doi":"10.1007/s13105-024-01063-6","DOIUrl":"10.1007/s13105-024-01063-6","url":null,"abstract":"<p><p>The increase in age-related comorbidities, such as cardiometabolic diseases, has become a global health priority. There is a growing need to find new parameters capable of improving the detection of cardiometabolic risk factors, and circulating endocannabinoids (eCBs) are a promising tool in this context. Here, we aimed to investigate the relationship between plasma levels of eCBs and their analogues with body composition and cardiometabolic risk factors in middle-aged adults. Seventy-two individuals (54% women; 53.6 ± 5.1 years old) were included in this study. Plasma levels of eCBs and analogues were determined using liquid chromatography-tandem mass spectrometry. Body composition was measured by dual-energy X-ray absorptiometry. Cardiometabolic risk factors (i.e., glucose and lipid profile, blood pressure, liver and renal parameters, and gonadal hormones) were also assessed. The plasma levels of 1- and 2-arachidonylglycerol (1-AG&2-AG) were positively correlated with adiposity (all r ≥ 0.23, P < 0.05). Interestingly, the plasma levels of 1-AG&2-AG, arachidonoylethanolamide, and palmitoyl-ethanolamide were positively correlated with the homeostatic model assessment index - Insulin Resistance (HOMA-IR) (all r ≥ 0.32, P < 0.01). Our results also showed that high levels of 1-AG&2-AG, arachidonoylethanolamide, linoleoyl ethanolamide, and palmitoleoyl ethanolamide were correlated with poorer liver (all r ≥ 0.27, P < 0.05), kidney (all r ≥ 0.24, P < 0.05), and gonadal function parameters (testosterone: all r > 0.26, P < 0.05, SHBG: 1-AG&2-AG r=-0.33, P < 0.01). The plasma levels of some eCBs and analogues are correlated with a worse cardiometabolic profile in middle-aged adults.</p>","PeriodicalId":16779,"journal":{"name":"Journal of physiology and biochemistry","volume":" ","pages":"173-184"},"PeriodicalIF":3.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142785773","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}
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