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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}
引用次数: 0
MicroRNA-enriched exosome as dazzling dancer between cancer and immune cells. 富含微RNA的外泌体是癌症细胞与免疫细胞之间的炫目舞者。
IF 3.7 3区 生物学
Journal of physiology and biochemistry Pub Date : 2024-11-01 Epub Date: 2024-09-24 DOI: 10.1007/s13105-024-01050-x
Chou-Yi Hsu, Abdulrahman T Ahmed, Pooja Bansal, Ahmed Hjazi, Hussein Riyadh Abdul Kareem Al-Hetty, Maytham T Qasim, Ibrokhim Sapaev, Mahamedha Deorari, Yasser Fakri Mustafa, Ahmed Elawady
{"title":"MicroRNA-enriched exosome as dazzling dancer between cancer and immune cells.","authors":"Chou-Yi Hsu, Abdulrahman T Ahmed, Pooja Bansal, Ahmed Hjazi, Hussein Riyadh Abdul Kareem Al-Hetty, Maytham T Qasim, Ibrokhim Sapaev, Mahamedha Deorari, Yasser Fakri Mustafa, Ahmed Elawady","doi":"10.1007/s13105-024-01050-x","DOIUrl":"10.1007/s13105-024-01050-x","url":null,"abstract":"<p><p>Exosomes are widely recognized for their roles in numerous biological processes and as intercellular communication mediators. Human cancerous and normal cells can both produce massive amounts of exosomes. They are extensively dispersed in tumor-modeling animals' pleural effusions, ascites, and plasma from people with cancer. Tumor cells interact with host cells by releasing exosomes, which allow them to interchange various biological components. Tumor growth, invasion, metastasis, and even tumorigenesis can all be facilitated by this delicate and complex system by modifying the nearby and remote surroundings. Due to the existence of significant levels of biomolecules like microRNA, exosomes can modulate the immune system's stimulation or repression, which in turn controls tumor growth. However, the role of microRNA in exosome-mediated communication between immunological and cancer cells is still poorly understood. This study aims to get the most recent information on the \"yin and yang\" of exosomal microRNA in the regulation of tumor immunity and immunotherapy, which will aid current cancer treatment and diagnostic techniques.</p>","PeriodicalId":16779,"journal":{"name":"Journal of physiology and biochemistry","volume":" ","pages":"811-829"},"PeriodicalIF":3.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142307985","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
Sphingosine 1-phosphate protective effect on human proximal tubule cells submitted to an in vitro ischemia model: the role of JAK2/STAT3. 1-磷酸肾上腺素对体外缺血模型中人近曲小管细胞的保护作用:JAK2/STAT3的作用
IF 3.7 3区 生物学
Journal of physiology and biochemistry Pub Date : 2024-11-01 Epub Date: 2024-08-19 DOI: 10.1007/s13105-024-01038-7
Juliane Lopes de Assis, Gloria Maria Ramalho Soares Grelle, Aline Marie Fernandes, Bárbara da Silva Aniceto, Pedro Pompeu, Fabiana Vieira de Mello, Rafael Garrett, Rafael Hospodar Felippe Valverde, Marcelo Einicker-Lamas
{"title":"Sphingosine 1-phosphate protective effect on human proximal tubule cells submitted to an in vitro ischemia model: the role of JAK2/STAT3.","authors":"Juliane Lopes de Assis, Gloria Maria Ramalho Soares Grelle, Aline Marie Fernandes, Bárbara da Silva Aniceto, Pedro Pompeu, Fabiana Vieira de Mello, Rafael Garrett, Rafael Hospodar Felippe Valverde, Marcelo Einicker-Lamas","doi":"10.1007/s13105-024-01038-7","DOIUrl":"10.1007/s13105-024-01038-7","url":null,"abstract":"<p><p>Acute kidney injury is a serious public health problem worldwide, being ischemia and reperfusion (I/R) the main lesion-aggravating factor that contributes to the evolution towards chronic kidney disease. Nonetheless, intervention approaches currently available are just considered palliative options. In order to offer an alternative treatment, it is important to understand key factors involved in the development of the disease including the rescue of the affected cells and/or the release of paracrine factors that are crucial for tissue repair. Bioactive lipids such as sphingosine 1-phosphate (S1P) have significant effects on the modulation of signaling pathways involved in tissue regeneration, such as cell survival, proliferation, differentiation, and migration. The main objective of this work was to explore the protective effect of S1P using human kidney proximal tubule cells submitted to a mimetic I/R lesion, via ATP depletion. We observed that the S1P pre-treatment increases cell survival by 50% and preserves the cell proliferation capacity of injured cells. We showed the presence of different bioactive lipids notably related to tissue repair but, more importantly, we noted that the pre-treatment with S1P attenuated the ischemia-induced effects in response to the injury, resulting in higher endogenous S1P production. All receptors but S1PR3 are present in these cells and the protective and proliferative effect of S1P/S1P receptors axis occur, at least in part, through the activation of the SAFE pathway. To our knowledge, this is the first time that S1PR4 and S1PR5 are referred in these cells and also the first indication of JAK2/STAT3 pathway involvement in S1P-mediated protection in an I/R renal model.</p>","PeriodicalId":16779,"journal":{"name":"Journal of physiology and biochemistry","volume":" ","pages":"831-843"},"PeriodicalIF":3.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142000213","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
Inhibin subunit beta B (INHBB): an emerging role in tumor progression. 抑制素亚基 beta B (INHBB):在肿瘤进展中的新角色。
IF 3.7 3区 生物学
Journal of physiology and biochemistry Pub Date : 2024-11-01 Epub Date: 2024-08-26 DOI: 10.1007/s13105-024-01041-y
Ying Liu, Qing Zhou, Guoying Zou, Wenling Zhang
{"title":"Inhibin subunit beta B (INHBB): an emerging role in tumor progression.","authors":"Ying Liu, Qing Zhou, Guoying Zou, Wenling Zhang","doi":"10.1007/s13105-024-01041-y","DOIUrl":"10.1007/s13105-024-01041-y","url":null,"abstract":"<p><p>The gene inhibin subunit beta B (INHBB) encodes the inhibin βB subunit, which is involved in forming protein members of the transforming growth factor-β (TGF-β) superfamily. The TGF-β superfamily is extensively involved in cell proliferation, differentiation, adhesion, movement, metabolism, communication, and death. Activins and inhibins, which belong to the TGF-β superfamily, were first discovered in ovarian follicular fluid. They were initially described as regulators of pituitary follicle-stimulating hormone (FSH) secretion both in vivo and in vitro. Later studies found that INHBB is expressed not only in reproductive organs such as the ovary, uterus, and testis but also in numerous other organs, including the brain, spinal cord, liver, kidneys, and adrenal glands. This wide distribution implies its involvement in the normal physiological functions of various organs; however, the mechanisms underlying these functions have not yet been fully elucidated. Recent studies suggest that INHBB plays a significant, yet complex role in tumorigenesis. It appears to have dual effects, promoting tumor progression in some contexts while inhibiting it in others, although these roles are not yet fully understood. In this paper, we review the different expression patterns, functions, and mechanisms of INHBB in normal and tumor tissues to illustrate the research prospects of INHBB in tumor progression.</p>","PeriodicalId":16779,"journal":{"name":"Journal of physiology and biochemistry","volume":" ","pages":"775-793"},"PeriodicalIF":3.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142055912","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
Mechanism of Mettl14 regulating AIM2 inflammasome activation and neuronal apoptosis and pyroptosis in spinal cord injury by mediating PPARγ m6A methylation. Mettl14 通过介导 PPARγ m6A 甲基化调节脊髓损伤中 AIM2 炎症小体激活、神经元凋亡和热凋亡的机制
IF 3.7 3区 生物学
Journal of physiology and biochemistry Pub Date : 2024-11-01 Epub Date: 2024-10-14 DOI: 10.1007/s13105-024-01047-6
Fan Wu, Liqun Li, Zhigang Li, Dabiao Zhou, Zhihui Huang, Dawei Sang, Chizi Hao
{"title":"Mechanism of Mettl14 regulating AIM2 inflammasome activation and neuronal apoptosis and pyroptosis in spinal cord injury by mediating PPARγ m6A methylation.","authors":"Fan Wu, Liqun Li, Zhigang Li, Dabiao Zhou, Zhihui Huang, Dawei Sang, Chizi Hao","doi":"10.1007/s13105-024-01047-6","DOIUrl":"10.1007/s13105-024-01047-6","url":null,"abstract":"<p><p>Spinal cord injury (SCI) represents a destructive pathological and neurological state. Methyltransferase-like 14 (Mettl14)-mediated m6A modification links to spinal cord injury (SCI), and we explored its mechanism. SCI mouse models were subjected to si-Mettl14 and si-negative control treatments and mouse behavior, pathological condition and apoptosis assessments. The oxygen/glucose deprivation (OGD)-induced spinal cord neuronal cell models were processed with si-Mettl14 and si-peroxisome proliferator-activated receptor γ (PPARγ) plasmids, and pcDNA3.1-YTHDF2 or synthetic dsDNA Poly(dA: dT), followed by viability and apoptosis evaluation by MTT and flow cytometry. Levels of Mettl14, PPARγ, and YTHDF2 mRNAs and proteins, AIM2 inflammasome activation-associated and pyroptosis marker proteins, PPARγ m6A methylation and pyroptosis-related inflammatory factors were determined by RT-qPCR, Western blot, Me-RIP and ELISA, with PPARγ mRNA stability and YTHDF2-PPARγ interaction assessed. Mettl14 and PPARγ m6A modification levels rose in SCI spinal cord tissues, while PPARγ levels dropped. Mettl14 knockdown dampened m6A modification, up-regulated PPARγ levels, weakened neuronal apoptosis, and ameliorated SCI in mice. OGD down-regulated PPARγ and accelerated OGD-induced neuronal apoptosis and pyroptosis via inducing Mettl14-mediated m6A modification. Mettl14 amplified PPARγ mRNA degradation and down-regulated PPARγ by mediating m6A methylation via the YTHDF2-dependent pathway. Mettl14 silencing-mediated PPARγ m6A methylation mitigated OGD-induced neuronal apoptosis and pyroptosis by inactivating AIM2 inflammasome. Mettl14 triggered activated AIM2 inflammasomes, promoted neuronal apoptosis and pyroptosis, and worsened SCI in SCI mice via mediating PPARγ m6A methylation. Mettl14 regulates AIM2 inflammasome activation, and redounds to spinal cord neuronal apoptosis and pyroptosis in SCI by mediating m6A methylation of PPARγ.</p>","PeriodicalId":16779,"journal":{"name":"Journal of physiology and biochemistry","volume":" ","pages":"881-894"},"PeriodicalIF":3.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142468315","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
Normobaric hypoxia accelerates high-intensity intermittent training-induced mitochondrial biogenesis (PGC-1α)- and dynamics (OPA1)-related protein expressions in rat gastrocnemius muscle. 常压低氧可加速高强度间歇训练诱导的大鼠腓肠肌线粒体生物生成(PGC-1α)和动力学(OPA1)相关蛋白的表达。
IF 3.7 3区 生物学
Journal of physiology and biochemistry Pub Date : 2024-11-01 Epub Date: 2024-10-18 DOI: 10.1007/s13105-024-01052-9
Shohei Dobashi, Toshinori Yoshihara, Yuji Ogura, Hisashi Naito
{"title":"Normobaric hypoxia accelerates high-intensity intermittent training-induced mitochondrial biogenesis (PGC-1α)- and dynamics (OPA1)-related protein expressions in rat gastrocnemius muscle.","authors":"Shohei Dobashi, Toshinori Yoshihara, Yuji Ogura, Hisashi Naito","doi":"10.1007/s13105-024-01052-9","DOIUrl":"10.1007/s13105-024-01052-9","url":null,"abstract":"<p><p>High-intensity intermittent training (HIIT) in a normobaric hypoxic environment enhances exercise capacity, possibly by increasing the mitochondrial content in skeletal muscle; however, the molecular mechanisms underlying these adaptations are not well understood. Therefore, we investigated whether HIIT under normobaric hypoxia can enhance the expression of proteins involved in mitochondrial biogenesis and dynamics in rat gastrocnemius muscle. Five-week-old male Wistar rats (n = 24) were randomly assigned to the following four groups: (1) sedentary under normoxia (20.9% O<sub>2</sub>) (NS), (2) training under normoxia (NT), (3) sedentary under normobaric hypoxia (14.5% O<sub>2</sub>) (HS), and (4) training under normobaric hypoxia (HT). The training groups in both conditions were engaged in HIIT on a treadmill five to six days per week for nine weeks. From the fourth week of the training period, the group assigned to hypoxic conditions was exposed to normobaric hypoxia. Forty-eight hours after completing the final training session, gastrocnemius muscles were surgically removed, and mitochondrial enzyme activity and mitochondrial biogenesis and dynamics regulatory protein levels were determined. Citrate synthase (CS) activity and mitochondrial oxygen phosphorylation (OXPHOS) subunits in the gastrocnemius muscle in the HT significantly exceeded those in the other three groups. Moreover, the levels of a master regulator of mitochondrial biogenesis, peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), and a mitochondrial fusion-related protein, optic atrophy 1 (OPA1), were significantly increased by HIIT under normobaric hypoxia. Our data indicates that HIIT and normobaric hypoxia increase the expression of mitochondrial biogenesis- and dynamics-related proteins in skeletal muscles.</p>","PeriodicalId":16779,"journal":{"name":"Journal of physiology and biochemistry","volume":" ","pages":"909-917"},"PeriodicalIF":3.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142468216","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
Apelin/APJ signaling in IGF-1-induced acute mitochondrial and antioxidant effects in spontaneously hypertensive rat myocardium. 自发性高血压大鼠心肌中 IGF-1 诱导的急性线粒体和抗氧化效应中的凋亡素/APJ 信号传导。
IF 3.7 3区 生物学
Journal of physiology and biochemistry Pub Date : 2024-11-01 Epub Date: 2024-10-25 DOI: 10.1007/s13105-024-01055-6
Alejandra M Yeves, Joshua Godoy Coto, Erica V Pereyra, Andrés J Medina, Luisa F González Arbelaez, Fiorella A Cavalli, Irene L Ennis
{"title":"Apelin/APJ signaling in IGF-1-induced acute mitochondrial and antioxidant effects in spontaneously hypertensive rat myocardium.","authors":"Alejandra M Yeves, Joshua Godoy Coto, Erica V Pereyra, Andrés J Medina, Luisa F González Arbelaez, Fiorella A Cavalli, Irene L Ennis","doi":"10.1007/s13105-024-01055-6","DOIUrl":"10.1007/s13105-024-01055-6","url":null,"abstract":"<p><p>IGF-1 and apelin are released in response to exercise training with beneficial effects. Previously we demonstrated that a swimming routine is effective to convert pathological into physiological cardiac hypertrophy, and that IGF-1 improves contractility and the redox state, in spontaneously hypertensive rats (SHR). Now, we hypothesize that the apelinergic pathway is involved in the cardioprotective effects of IGF-1 in the SHR. We assessed the redox state and mitochondrial effects of IGF-1 or apelin in the presence/absence of AG1024 or ML221 [pharmacological antagonists of IGF1 (IGF1R) and apelin (APJ) receptors, respectively] in SHR isolated cardiomyocytes or perfused hearts. Acute IGF-1 (10 nmol/L) significantly: -reduced H<sub>2</sub>O<sub>2</sub> production (IGF-1:62 ± 6; control:100 ± 8.1, %), -increased the activity of superoxide dismutase (IGF-1:193 ± 17, control: 100 ± 13,%), -prevented H<sub>2</sub>O<sub>2</sub>-induced ΔΨm loss (TMRE<sub>F10min/F0 min</sub>: IGF-1:0.93 ± 0.017, control: 0.72 ± 0.029), -reduced mitochondrial permeability transition pore (mPTP) opening estimated by the calcium retention capacity (nmol/mg protein, IGF-1:251 ± 34, control:112 ± 5), and -increased P-AMPK (IGF-1:129 ± 0.9, control: 100 ± 2%) and P-AKT (IGF-1:143 ± 17 control:100 ± 6, %). These effects were suppressed not only by the antagonism of IGF1R but also of APJ. Moreover, IGF-1 significantly increased APJ (IGF-1:198 ± 29 control:100 ± 15,%) and apelin mRNAs (IGF-1:251 ± 48, control:100 ± 6,%). On the other hand, an equipotent dose of exogenous apelin (50 nmol/L) emulated IGF-1 effects being cancelled by the antagonism of APJ however not by AG1024. IGF-1/IGF1R stimulates the apelinergic pathway, improving the redox balance and mitochondria status in the pathologically hypertrophied myocardium of the SHR.</p>","PeriodicalId":16779,"journal":{"name":"Journal of physiology and biochemistry","volume":" ","pages":"949-959"},"PeriodicalIF":3.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142502601","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
TAF15 inhibits p53 nucleus translocation and promotes HCC cell 5-FU resistance via post-transcriptional regulation of UBE2N. TAF15 通过转录后调控 UBE2N 抑制 p53 核转位并促进 HCC 细胞对 5-FU 的耐受。
IF 3.7 3区 生物学
Journal of physiology and biochemistry Pub Date : 2024-11-01 Epub Date: 2024-10-24 DOI: 10.1007/s13105-024-01053-8
Jiayan Fang, Mengqi Zou, Mei Yang, Yejia Cui, Rong Pu, Yufeng Yang
{"title":"TAF15 inhibits p53 nucleus translocation and promotes HCC cell 5-FU resistance via post-transcriptional regulation of UBE2N.","authors":"Jiayan Fang, Mengqi Zou, Mei Yang, Yejia Cui, Rong Pu, Yufeng Yang","doi":"10.1007/s13105-024-01053-8","DOIUrl":"10.1007/s13105-024-01053-8","url":null,"abstract":"<p><p>Chemotherapy resistance is an important factor responsible for the low 5-year survival rate of hepatocellular carcinoma (HCC) patients. Ubiquitin-conjugating enzyme E2N (UBE2N) is a cancer-associated ubiquitin-conjugating enzyme that is expressed in HCC tissues, and its high expression is associated with a poor prognosis. This study explored the role played by UBE2N in development of 5-fluorouracil (5-FU) resistance in HCC cells. Three HCC cell lines (HepG2 [p53 wild type], Huh7 [p53 point mutant type], Hep3B [p53 non-expression type]), and one normal liver cell line (MIHA) were used in our present study. The IC50 value of 5-FU was determined using a cell counting kit-8 (CCK-8) assay. Cell viability was assessed by colony formation assays. TUNEL assays and flow cytometry were used to analyze cell apoptosis. RNA pull-down and RNA immunoprecipitation (RIP) assays were performed to confirm the binding relationship between UBE2N mRNA and TAF15 protein. Our results showed that TAF15 and UBE2N were highly expressed in HCC cells. UBE2N inhibited the translocation of p53 protein into the cell nucleus to increase 5-FU resistance, as reflected by an increased IC50 value, an increase in cell viability, and a reduction in cell apoptosis. Overexpression of p53 reduced 5-FU resistance, but that effect could be reversed by UBE2N overexpression. TAF15 protein bound to and stabilized UBE2N mRNA, thereby inhibiting p53 translocation into the nucleus and promoting 5-FU resistance in HCC cells. Collectively, our present study identified a novel mechanism by which TAF15/UBE2N regulates p53 distribution to increase 5-FU resistance. Our results also suggest potential therapeutic strategies for treating HCC.</p>","PeriodicalId":16779,"journal":{"name":"Journal of physiology and biochemistry","volume":" ","pages":"919-933"},"PeriodicalIF":3.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142502602","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
Renal denervation ameliorates atrial remodeling in type 2 diabetic rats by regulating mitochondrial dynamics. 通过调节线粒体动力学,肾脏去神经化可改善 2 型糖尿病大鼠的心房重塑。
IF 3.7 3区 生物学
Journal of physiology and biochemistry Pub Date : 2024-11-01 Epub Date: 2024-10-22 DOI: 10.1007/s13105-024-01054-7
Jun-Yu Huo, Can Hou, Xiao-Long Li, Ling Yang, Wan-Ying Jiang
{"title":"Renal denervation ameliorates atrial remodeling in type 2 diabetic rats by regulating mitochondrial dynamics.","authors":"Jun-Yu Huo, Can Hou, Xiao-Long Li, Ling Yang, Wan-Ying Jiang","doi":"10.1007/s13105-024-01054-7","DOIUrl":"10.1007/s13105-024-01054-7","url":null,"abstract":"<p><p>There is no effective treatment for diabetes-related atrial remodeling currently. This study aimed to investigate the effects of renal denervation (RDN) on diabetes-related atrial remodeling and explore the related mechanisms. A type 2 diabetes mellitus model was established by high-fat diet feeding and low-dose streptozotocin injection in Sprague‒Dawley rats. After successful modeling, the diabetic rats were randomly assigned to two groups according to whether they were subjected to RDN or sham RDN surgery. At the end of the experiment, cardiac function and structure were evaluated by echocardiography and histology, respectively. Mitochondrial morphology, function and mitochondrial dynamics were assessed by multiple methods. Mdivi1 was used to verify the mechanism by which RDN improves atrial remodeling. In the 10th week, diabetic rats exhibited obvious atrial remodeling, including atrial enlargement and diastolic dysfunction. Pathological staining showed that diabetic rats had cardiomyocyte hypertrophy and interstitial fibrosis in atrial tissues. In terms of mitochondrial morphology and function, diabetic rats exhibited fragmented mitochondria, reduced adenosine triphosphate production and decreased mitochondrial membrane potential levels. Abnormal mitochondrial dynamics in diabetic rats were characterized by the inhibition of mitochondrial fusion, excessive mitochondrial fission, and the suppression of mitophagy. However, RDN effectively ameliorated diabetes-induced pathological atrial remodeling. In addition, RDN significantly improved mitochondrial morphological and functional abnormalities and corrected the disorders of mitochondrial dynamics. Furthermore, the protective effects of RDN against atrial remodeling were related to the regulation of mitochondrial dynamics. RDN prevented diabetes-induced atrial remodeling. These protective effects might be related to improvements in mitochondrial dynamics.</p>","PeriodicalId":16779,"journal":{"name":"Journal of physiology and biochemistry","volume":" ","pages":"935-948"},"PeriodicalIF":3.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142468326","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
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