Pflugers Archiv : European journal of physiology最新文献

{"title":"Diet-induced impairment of skeletal muscle and adipose tissue metabolic homeostasis and its prevention by probiotic administration.","authors":"Angela Di Porzio, Valentina Barrella, Luisa Cigliano, Gianluigi Mauriello, Antonio Dario Troise, Andrea Scaloni, Susanna Iossa, Arianna Mazzoli","doi":"10.1007/s00424-024-03041-9","DOIUrl":"10.1007/s00424-024-03041-9","url":null,"abstract":"<p><p>Western dietary pattern is one of the main contributors to the increased risk of obesity and chronic diseases, through oxidative stress and inflammation, that are the two key mechanisms targeting metabolic organs, such as skeletal muscle and adipose tissue. The chronic exposure to high levels of dietary fatty acids can increase the amount of intramyocellular lipids in skeletal muscle, altering glucose homeostasis and contributing to a reduction in mitochondrial oxidative capacity. Probiotic administration is a promising approach as preventive strategy to attenuate metabolic damage induced by Western diet. Here, we investigated the beneficial effect of Limosillactobacillus reuteri DSM 17938 on the inflammatory state and oxidative balance in the skeletal muscle and adipose tissue of adult rats fed a western diet for 8 weeks, focusing on the role of skeletal muscle mitochondria. Limosillactobacillus reuteri DSM 17938 administration protected the skeletal muscle from mitochondrial dysfunction and oxidative stress, preventing the establishment of inflammation and insulin resistance. Interestingly, a further beneficial effect of the probiotic was exerted on body composition, favoring the deposition of protein mass and preventing adipose tissue hypertrophy and inflammation. These results open the possibility for the use of this probiotic in therapeutic approaches for nutrition-related diseases.</p>","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":" ","pages":"223-239"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142625942","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TRPC3-mediated NFATc1 calcium signaling promotes triple negative breast cancer migration through regulating glypican-6 and focal adhesion.","authors":"Yan Wang, Xiaosheng Zhuang, Yanxiang Qi, Lung Yiu, Zhenping Li, Yuk Wah Chan, Xianji Liu, Suk Ying Tsang","doi":"10.1007/s00424-024-03030-y","DOIUrl":"10.1007/s00424-024-03030-y","url":null,"abstract":"<p><p>Canonical transient receptor potential isoform 3 (TRPC3), a calcium-permeable non-selective cation channel, has been reported to be upregulated in breast cancers and a modulator of cell migration. Calcium-sensitive transcription factor NFATc1, which is important for cell migration, was shown to be frequently activated in triple negative breast cancer (TNBC) biopsy tissues. However, whether TRPC3-mediated calcium influx would activate NFATc1 and affect the migration of TNBC cells, and, if yes, the underlying mechanisms involved, remain to be investigated. By immunostaining followed by confocal microscopy, TNBC lines MDA-MB-231 and BT-549 were both found to express TRPC3 on their plasma membrane while ER⁺ line MCF-7 and HER2⁺ line SK-BR3 do not. Blockade of TRPC3 by pharmacological inhibitor Pyr3 or stable knockdown of TRPC3 by lentiviral vector both inhibited cell migration as measured by wound healing assay. Importantly, blocking TRPC3 by Pyr3 or knockdown of TRPC3 both caused the translocation of NFATc1 from the nucleus to the cytosol as revealed by confocal microscopy. Interestingly, NFATc1 was found to bind to the promoter of glypican 6 (GPC6) as determined by chromatin immunoprecipitation assay. Consistently, knockdown of TRPC3 decreased the expression of GPC6 as revealed by western blotting. Moreover, long-term knockdown of GPC6 by lentiviral vector also consistently decreased the migration of TNBC cells. Intriguingly, GPC6 proteins physically interact with vinculin in MDA-MB-231 as determined by co-immunoprecipitation. Blockade of TRPC3, knockdown of TRPC3 or knockdown of GPC6 all induced larger, stabilized actin-bound peripheral focal adhesion (FA) formations in TNBC cells as determined by co-staining of actin and vinculin followed by confocal microscopy. These large, stabilized actin-bound peripheral FAs indicated a defective FA turnover, and were reported to be responsible for impairing directed cell migration. Our results suggest that, in TNBC cells, calcium influx through TRPC3 channel positively regulates NFATc1 nuclear translocation and GPC6 expression, which maintains the dynamics of FA turnover and optimal cell migration. Our study reveals a novel TRPC3-NFATc1-GPC6-vinculin signaling cascade in maintaining the migration of TNBC cells.</p>","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":" ","pages":"253-272"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11762004/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142472226","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lessons from a model: early glucagon dysfunction in type 2 diabetes.","authors":"Shawn Duckett, Patrick E MacDonald","doi":"10.1007/s00424-024-03062-4","DOIUrl":"10.1007/s00424-024-03062-4","url":null,"abstract":"","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":" ","pages":"201-203"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142953143","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Like a Phoenix Reborn from the Ashes: TASK-5 - Commentary to Rinne & Schick et al.","authors":"Guiscard Seebohm","doi":"10.1007/s00424-024-03057-1","DOIUrl":"10.1007/s00424-024-03057-1","url":null,"abstract":"","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":" ","pages":"205-206"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11761766/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142953194","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intracellular cAMP signaling-induced Ca²⁺ influx mediated by calcium homeostasis modulator 1 (CALHM1) in human odontoblasts.","authors":"Maki Kimura, Sachie Nomura, Takehito Ouchi, Ryuya Kurashima, Rei Nakano, Hinako Sekiya, Hidetaka Kuroda, Kyosuke Kono, Yoshiyuki Shibukawa","doi":"10.1007/s00424-024-03038-4","DOIUrl":"10.1007/s00424-024-03038-4","url":null,"abstract":"<p><p>In odontoblasts, intracellular Ca²⁺ signaling plays key roles in reactionary dentin formation and generation of dentinal pain. Odontoblasts also express several G_s protein-coupled receptors that promote production of cyclic AMP (cAMP). However, the crosstalk between intracellular cAMP and Ca²⁺ signaling, as well as the role of cAMP in the cellular functions of odontoblasts, remains unclear. In this study, we measured intracellular cAMP levels and intracellular free Ca²⁺ concentration ([Ca²⁺]_i). We also investigated the effect of intracellular cAMP on mineralization by the odontoblasts. In the presence of extracellular Ca²⁺, the application of forskolin (adenylyl cyclase activator) or isoproterenol (G_s protein-coupled beta-2 adrenergic receptor agonist) increased intracellular cAMP levels and [Ca²⁺]_i in odontoblasts. The [Ca²⁺]_i increases could not be observed by removing extracellular Ca²⁺, indicating that cAMP is capable to activate Ca²⁺ entry. Forskolin-induced [Ca²⁺]_i increase was inhibited by a protein kinase A inhibitor in odontoblasts. The [Ca²⁺]_i increase was sensitive to Gd³⁺, 2APB, or Zn²⁺ but not verapamil, ML218, or La³⁺. In immunofluorescence analyses, odontoblasts were immunopositive for calcium homeostasis modulator 1 (CALHM1), which was found close to ionotropic ATP receptor subtype, P2X₃ receptors. When CALHM1 was knocked down, forskolin-induced [Ca²⁺]_i increase was suppressed. Alizarin red and von Kossa staining showed that forskolin decreased mineralization. These findings suggest that activation of adenylyl cyclase elicited increases in the intracellular cAMP level and Ca²⁺ influx via protein kinase A activation in odontoblasts. Subsequent cAMP-dependent Ca²⁺ influx was mediated by CALHM1 in odontoblasts. In addition, the intracellular cAMP signaling pathway in odontoblasts negatively mediated dentinogenesis.</p>","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":" ","pages":"273-290"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11762207/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142623485","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cardioprotective effects of H3 receptor activation could be double-sided: insights from isoproterenol-induced cardiac injury.","authors":"H Fehmi Özel, Mustafa Özbek, Merve Temel Özden, H Seda Vatansever","doi":"10.1007/s00424-024-03039-3","DOIUrl":"10.1007/s00424-024-03039-3","url":null,"abstract":"<p><p>Histamine H3 receptors (H3Rs) are known to modulate neurotransmitter release in the nervous system, but their role in cardiac injury remains unclear. The present study aimed to investigate the cardioprotective role of H3Rs in a mouse model of myocardial injury. Forty BALB/c male mice were divided into four groups: Control (SF), Isoproterenol (ISO), Imetit (IMT), and IMT + ISO. The IMT and IMT + ISO groups were pretreated orally with 10 mg/kg imetit-dihydrobromide(imetit) for 7 days. In the last 2 days, the ISO and IMT + ISO groups received a subcutaneous injection of 85 mg/kg isoproterenol to induce myocardial ischemia. Electrocardiogram (ECG) recordings were obtained, and heart tissues were analyzed histopathologically. The results demonstrated that the administration of imetit resulted in the prolongation of the PR interval in the IMT group. QRS and QT intervals were prolonged in the ISO group. The J-wave area in the ISO group was significantly larger than in the other groups. Histopathological analyses revealed the presence of small vacuoles, inflammatory cell infiltration, and collagen aggregates in cardiomyocytes in the ISO group. No significant cellular changes were observed in the IMT group, in contrast. The IMT + ISO group exhibited fewer ischemic findings than the ISO group. Immunohistochemical analyses revealed positive H3R immunoreactivity in all groups. Imetit pretreatment increased the immunoreactivity of H3Rs in both the IMT and IMT + ISO groups. The findings of this study suggest that H3Rs may be present on the postsynaptic side in cardiac myocytes, in addition to adrenergic presynaptic nerve endings. Furthermore, imetit has been found to significantly reduce the effects of myocardial ischemia by activating H3Rs. The better characterization of the postsynaptic role of H3Rs offers potential for the development of new therapeutic strategies.</p>","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":" ","pages":"291-301"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142558462","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Estrogen hindrance escalates inflammation and neurodegeneration in the hippocampal regions of collagen-induced arthritis female Sprague-Dawley rats.","authors":"Zuo Hao Lee, Wong Siew Tung, Kabileshvaran A/L Jana Santhiran, Huma Shahzad, Nelli Giribabu, Naguib Salleh","doi":"10.1007/s00424-024-03032-w","DOIUrl":"10.1007/s00424-024-03032-w","url":null,"abstract":"<p><p>This study aims to investigate the effect of estrogen hindrance, i.e., menopause in women for instance with rheumatoid arthritis on the brain hippocampal region by using collagen-induced arthritis (CIA) female rat model (RA). CIA was induced in female rats by injecting bovine type II collagen and incomplete Freund's adjuvant. Estrogen receptor antagonist, fulvestrant (Ful), was given to RA rats to create estrogen hindrance. Control (C) and RA rats were injected with saline and DMSO, respectively, while RA + Ful rats received a 7-day fulvestrant injection. Following experiment completion, rats were sacrificed, and brains were harvested. Brains were stained with H&E and cresyl violet staining and morphological changes in the hippocampus were identified. Additionally, oxidative stress, inflammatory, and apoptosis markers' levels in the hippocampus were analyzed by qPCR, ELISA, and immunohistochemistry techniques. RA + Ful rats showed neuronal atrophy and reduced neurogenesis in the hippocampal regions. NOX4, NF-κB, IL-1β, IL-6, TNF-α, IKK-β, and Bax protein expression levels in the hippocampus were increased, whereas hippocampal Bcl-2, caspase-3, caspase-9, and IGF-1R protein expression levels were decreased. Furthermore, RA + Ful rats had lower levels of antioxidants PON-1 and catalase in the hippocampal regions. The changes in these molecular markers were statistically significant when compared to RA rats without Ful treatment (p < 0.05). Estrogen hindrance exaggerated oxidative stress, inflammation, and apoptosis which resulted in neuronal degeneration in the hippocampal regions in rheumatoid arthritis.</p>","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":" ","pages":"317-332"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142682405","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel neural pathways targeted by GLP-1R agonists and bariatric surgery.","authors":"Mohammed K Hankir, Thomas A Lutz","doi":"10.1007/s00424-024-03047-3","DOIUrl":"10.1007/s00424-024-03047-3","url":null,"abstract":"<p><p>The glucagon-like peptide 1 receptor (GLP-1R) agonist semaglutide has revolutionized the treatment of obesity, with other gut hormone-based drugs lined up that show even greater weight-lowering ability in obese patients. Nevertheless, bariatric surgery remains the mainstay treatment for severe obesity and achieves unparalleled weight loss that generally stands the test of time. While their underlying mechanisms of action remain incompletely understood, it is clear that the common denominator between GLP-1R agonists and bariatric surgery is that they suppress food intake by targeting the brain. In this Review, we highlight recent preclinical studies using contemporary neuroscientific techniques that provide novel concepts in the neural control of food intake and body weight with reference to endogenous GLP-1, GLP-1R agonists, and bariatric surgery. We start in the periphery with vagal, intestinofugal, and spinal sensory nerves and then progress through the brainstem up to the hypothalamus and finish at non-canonical brain feeding centers such as the zona incerta and lateral septum. Further defining the commonalities and differences between GLP-1R agonists and bariatric surgery in terms of how they target the brain may not only help bridge the gap between pharmacological and surgical interventions for weight loss but also provide a neural basis for their combined use when each individually fails.</p>","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":" ","pages":"171-185"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11761532/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142791771","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fatiguing high-intensity intermittent exercise depresses maximal Na⁺-K⁺-ATPase activity in human skeletal muscle assessed using a novel NADH-coupled assay.","authors":"Jeppe F Vigh-Larsen, Sara M Frangos, Kristian Overgaard, Graham P Holloway, Magni Mohr","doi":"10.1007/s00424-024-03036-6","DOIUrl":"10.1007/s00424-024-03036-6","url":null,"abstract":"<p><p>The Na⁺-K⁺-ATPase is a critical regulator of ion homeostasis during contraction, buffering interstitial K⁺ accumulation, which is linked to muscle fatigue during intense exercise. Within this context, we adopted a recently reported methodology to examine exercise-induced alterations in maximal Na⁺-K⁺-ATPase activity. Eighteen trained healthy young males completed a repeated high-intensity cycling protocol consisting of three periods (EX1-EX3) of intermittent exercise. Each period comprised 10 × 45-s cycling at ~ 105% W_max and a repeated sprint test. Muscle biopsies were sampled at baseline and after EX3 for determination of maximal in vitro Na⁺-K⁺-ATPase activity. Blood was drawn after each period and in association with a 2-min cycling test at a standardized high intensity (~ 90% W_max) performed before and after the session to assess plasma K⁺ accumulation. Further, a 5-h recovery period with the ingestion of carbohydrate or placebo supplementation was implemented to explore potential effects of carbohydrate availability before sampling a final biopsy and repeating all tests. A ~ 12% reduction in maximal Na⁺-K⁺-ATPase activity was demonstrated following EX3 compared to baseline (25.2 ± 3.9 vs. 22.4 ± 4.8 μmol·min^-1·g^-1 protein, P = 0.039), which was sustained at the recovery time point (~ 15% decrease compared to baseline to 21.6 ± 5.9 μmol·min^-1·g^-1 protein, P = 0.008). No significant effect of carbohydrate supplementation was observed on maximal Na⁺-K⁺-ATPase activity after recovery (P = 0.078). In conclusion, we demonstrate an exercise-induced depression of maximal Na⁺-K⁺-ATPase activity following high-intensity intermittent exercise, which was sustained during a 5-h recovery period and unrelated to carbohydrate availability under the present experimental conditions. This was shown using a novel NADH coupled assay and confirms previous findings using other methodological approaches.</p>","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":" ","pages":"303-316"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11761784/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142623480","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Physiological simulation of atrial-ventricular mechanical interaction in male rats during the cardiac cycle.","authors":"Alexandr Balakin, Yuri Protsenko","doi":"10.1007/s00424-024-03015-x","DOIUrl":"10.1007/s00424-024-03015-x","url":null,"abstract":"<p><p>Adequate assessment of the contribution of the different phases of atrial mechanical activity to the value of ejection volume and pressure developed by the ventricle is a complex and important experimental and clinical problem. A new method and an effective algorithm for controlling the interaction of isolated rat right atrial and right ventricular strips during the cardiac cycle were developed and tested in a physiological experiment. The presented functional model is flexible and has the ability to change many parameters (temperature, pacing rate, excitation delay, pre- and afterload levels, transfer length, and force scaling coefficients) to simulate different types of cardiac pathologies. For the first time, the contribution of the duration of the excitation delay of the right ventricular strips to the amount of work performed by the muscles during the cardiac cycle was evaluated. Changes in the onset of atrial systole and the delay in activation of ventricular contraction may lead to a reduction in cardiac stroke volume, which should be considered in the diagnosis and treatment of cardiovascular disease and in resynchronization therapy.</p>","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":" ","pages":"159-167"},"PeriodicalIF":2.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142120430","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}