American journal of physiology. Regulatory, integrative and comparative physiology最新文献

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Comparison of thermoregulatory, cardiovascular, and immune responses to different passive heat therapy modalities. 不同被动热疗方式对体温调节、心血管和免疫反应的比较。
IF 2.2 3区 医学
American journal of physiology. Regulatory, integrative and comparative physiology Pub Date : 2025-07-01 Epub Date: 2025-05-07 DOI: 10.1152/ajpregu.00012.2025
Jessica K Atencio, Emma L Reed, Karen Wiedenfeld Needham, Kathryn M Lucernoni, Lindan N Comrada, John R Halliwill, Christopher T Minson
{"title":"Comparison of thermoregulatory, cardiovascular, and immune responses to different passive heat therapy modalities.","authors":"Jessica K Atencio, Emma L Reed, Karen Wiedenfeld Needham, Kathryn M Lucernoni, Lindan N Comrada, John R Halliwill, Christopher T Minson","doi":"10.1152/ajpregu.00012.2025","DOIUrl":"10.1152/ajpregu.00012.2025","url":null,"abstract":"<p><p>This study compared thermoregulatory, cardiovascular, and immune responses to acute hot water immersion (HWI), traditional sauna (TRAD), and far infrared sauna (FIR). Twenty healthy adults (10 F; age 24 ± 4 yr) completed three bouts of passive heating: HWI (45 min at 40.5°C), TRAD (3 × 10 min at 80°C), and FIR (45 min at 45-65°C) separated by at least 1 wk. Core temperature (T<sub>c</sub>) was measured at baseline and every 5-min during heating. Cardiac output (Q<sub>c</sub>) was measured before, halfway, and at the end of heating using the open-circuit acetylene wash-in method. Venous blood was collected at baseline and ∼20-min, 24-, and 48-h postheating for measurement of inflammatory cytokines and immune cell populations. The overall change in T<sub>c</sub> from baseline to end of heating was greater in HWI [+1.1°C (0.9, 1.3)] vs. TRAD [+0.4°C (0.2, 0.6), <i>P</i> < 0.01], HWI vs. FIR [+0.0°C (-0.1, 0.2), <i>P</i> < 0.01], and TRAD vs. FIR (<i>P</i> = 0.02). Q<sub>c</sub> increased to the greatest extent in HWI [+3.7 L/min (2.9, 4.4)] vs. TRAD [+2.3 L/min (1.8, 2.8), <i>P</i> < 0.01] and HWI vs. FIR [+1.6 L/min (1.2, 2.1), <i>P</i> < 0.01], with no difference between TRAD vs. FIR (<i>P</i> = 0.06). HWI was the only heating modality to elicit inflammatory and immune responses as evidenced by increased interleukin-6 (IL-6) concentration postheating [+0.386 pg/mL (0.093, 0.680), <i>P</i> = 0.04], NK cells 24-h postheating (<i>P</i> = 0.03), and CD8<sup>+</sup> T cells at 24 (<i>P</i> = 0.02) and 48 h postheating (<i>P</i> = 0.03). A single bout of hot water immersion elicits the greatest thermoregulatory, cardiovascular, and immune responses compared with both sauna modalities.<b>NEW & NOTEWORTHY</b> Our goal was to compare three widely utilized modalities of passive heating in the manner that they are most commonly used for heat therapy. We have demonstrated that hot water immersion leads to the greatest thermoregulatory, cardiovascular, and immune responses compared with both traditional and far infrared saunas in young, healthy adults. Far infrared sauna heating was the least impactful on raising body core temperature and the resulting cardiovascular and immune responses.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R20-R35"},"PeriodicalIF":2.2,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143962645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Evidence for potentiation in sympathetic neurovascular transduction following exercise in normotensive adults. 正常血压成人运动后交感神经血管传导增强的证据。
IF 2.2 3区 医学
American journal of physiology. Regulatory, integrative and comparative physiology Pub Date : 2025-07-01 Epub Date: 2025-06-09 DOI: 10.1152/ajpregu.00084.2025
Massimo Nardone, Julian C Bommarito, Kathryn N Pfundt, Samuel Amanual, Yeshale Chetty, Philip J Millar
{"title":"Evidence for potentiation in sympathetic neurovascular transduction following exercise in normotensive adults.","authors":"Massimo Nardone, Julian C Bommarito, Kathryn N Pfundt, Samuel Amanual, Yeshale Chetty, Philip J Millar","doi":"10.1152/ajpregu.00084.2025","DOIUrl":"10.1152/ajpregu.00084.2025","url":null,"abstract":"<p><p>Vascular conductance increases following a single bout of dynamic exercise, whereas sympathetic nerve traffic commonly appears unchanged. Discordance between vascular and sympathetic responses may reflect modulation in vasoconstrictor responsiveness. The primary study objective was to evaluate sympathetic neurovascular transduction following cycling exercise. The secondary objective was to explore mechanisms contributing to altered sympathetic neurovascular transduction by manipulating limb vascular conductance using local heating of the foot. We hypothesized that sympathetic neurovascular transduction would decrease following cycling exercise but would be unchanged by lower limb heating. Sixteen adults (22 ± 3 yr; 43 ± 8 mL·kg<sup>-1</sup>·min<sup>-1</sup>; 8 females) underwent measurements of heart rate (electrocardiography), mean arterial pressure (photoplethysmography), muscle sympathetic nerve activity (MSNA; microneurography), and femoral vascular conductance (FVC; duplex ultrasound) across three interventions: cycling exercise [60 min, 60% peak oxygen consumption (V̇O<sub>2peak</sub>), <i>n</i> = 16], time control (60 min, <i>n</i> = 16), and lower limb heating (foot submersion into 40°C water, <i>n</i> = 9). MSNA-FVC transduction was quantified using signal averaging. Compared with control, exercise did not alter MSNA (<i>P</i> = 0.72) but increased FVC (<i>P</i> < 0.01) and MSNA-FVC transduction (-8.6 ± 4.5 vs. -15.1 ± 5.7 mL/min/100 mmHg; <i>P</i> < 0.01). Compared with exercise, heating did not alter MSNA (<i>P</i> = 0.71) and tended to increases FVC (<i>P</i> = 0.09). However, increases in MSNA-FVC transduction following exercise tended to persist when compared with heating (-8.7 ± 8.0 vs. -15.1 ± 5.9 mL/min/100 mmHg; <i>P</i> = 0.06). Contrary to our hypothesis, these findings provide evidence for potentiated sympathetic neurovascular transduction following acute cycling exercise in healthy adults. The observed increase in neurovascular transduction appears independent of resting vasomotor tone.<b>NEW & NOTEWORTHY</b> Following cycling exercise, leg vascular conductance increases, whereas sympathetic nerve traffic is unchanged in young healthy adults. Discordant vascular and sympathetic responses may reflect modulation in vasoconstrictor responsiveness. The current study demonstrated that signal-averaged sympathetic neurovascular transduction was increased by ∼75% following a single bout of cycling exercise. Secondary experiments using local heating suggest that potentiation in sympathetic neurovascular transduction after exercise may occur independent of changes in resting vascular conductance.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R195-R203"},"PeriodicalIF":2.2,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144257134","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Effect of Pre-exercise Dietary Nitrate on Skeletal Muscle Blood Flow in a Rat Model of Pulmonary Hypertension. 运动前膳食硝酸盐对肺动脉高压模型大鼠骨骼肌血流的影响。
IF 2.2 3区 医学
American journal of physiology. Regulatory, integrative and comparative physiology Pub Date : 2025-07-01 DOI: 10.1152/ajpregu.00037.2025
Gary Marshall Long, Ashley D Giourdas, Amanda J Fisher, Tim Lahm, Andrew R Coggan, Mary Beth Brown
{"title":"Effect of Pre-exercise Dietary Nitrate on Skeletal Muscle Blood Flow in a Rat Model of Pulmonary Hypertension.","authors":"Gary Marshall Long, Ashley D Giourdas, Amanda J Fisher, Tim Lahm, Andrew R Coggan, Mary Beth Brown","doi":"10.1152/ajpregu.00037.2025","DOIUrl":"https://doi.org/10.1152/ajpregu.00037.2025","url":null,"abstract":"<p><p>Skeletal muscle dysfunction contributes to exercise intolerance in patients with pulmonary arterial hypertension (PAH). Reduced blood flow to skeletal muscle has been demonstrated in a rat model of the disease. We investigated the effect of acute nitrate (NO<sub>3</sub><sup>-</sup>) ingestion via beetroot juice (BRJ) on exercising muscle blood flow, and on plasma and muscle nitrate (NO<sub>3</sub><sup>-</sup>), nitrite (NO<sub>2</sub><sup>-</sup>) and cyclic GMP (cGMP) in male Sprague Dawley rats (~200 g, n=24) with monocrotaline-induced (60 mg/kg) PH. Muscle blood flow was assessed at rest and during treadmill running using fluorescent microspheres. Despite higher plasma NO<sub>3</sub><sup>-</sup> (756 ± 118 vs 63 ± 22 μmol/L p=<0.001) and NO<sub>2</sub><sup>-</sup> (0.63 ± 0.10 vs. 0.24 ± 0.04 μmol/L p=0.003), no difference between BRJ and PL was observed in either resting (p=0.88) or exercising (p=0.42) blood flow. Only NO<sub>3</sub><sup>-</sup> was higher in BRJ vs. PL for both the soleus (sol: 261 ± 20 vs. 123 ± 18 vs μmol/kg, p=<0.0005) and vastus lateralis (VL: 176 ± 34 vs. 86 ± 14 μmol/kg, p=0.02), with no differences for NO<sub>2</sub><sup>-</sup> (sol: 1.9 ± 0.2 vs.1.7 ± 0.3 μmol/kg, p=0.49; VL: 1.04 ± 0.2 vs. 1.03 ± 0.2 μmol/kg, p=0.97) or cGMP (sol: 4.8 ± 2.1 vs. 3.9 ± 1.5 vs. nmol/kg, p=0.22; VL 6.0 ± 3.8 vs. 5.8 ±3.2 nmol/kg, p=0.91). In a rat model of severe PH, acute BRJ dosing increases circulating and muscle NO<sub>3</sub><sup>-</sup> but does not alter muscle blood flow. Absence of change in muscle NO<sub>2</sub><sup>-</sup> and cGMP suggest insufficiently altered downstream NO signaling with BRJ supplementation.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144537772","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Role of the organum vasculosum of the lamina terminalis in the physiopathology of 2-kidney-1-clip hypertension in rats. 聚焦于“终板血管器官参与肾血管性高血压的神经体液机制”。
IF 2.2 3区 医学
American journal of physiology. Regulatory, integrative and comparative physiology Pub Date : 2025-07-01 Epub Date: 2025-06-13 DOI: 10.1152/ajpregu.00039.2025
Camila F Roncari, Richard B David
{"title":"Role of the organum vasculosum of the lamina terminalis in the physiopathology of 2-kidney-1-clip hypertension in rats.","authors":"Camila F Roncari, Richard B David","doi":"10.1152/ajpregu.00039.2025","DOIUrl":"10.1152/ajpregu.00039.2025","url":null,"abstract":"","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R184-R185"},"PeriodicalIF":2.2,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144293210","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The influence of sex on fiber-specific indices of oxidative capacity in human skeletal muscle. 性别对人体骨骼肌氧化能力纤维特异性指标的影响。
IF 2.2 3区 医学
American journal of physiology. Regulatory, integrative and comparative physiology Pub Date : 2025-07-01 Epub Date: 2025-05-23 DOI: 10.1152/ajpregu.00298.2024
Celine Bailleul, Nathan Hodson, Sidney Abou Sawan, Dinesh Kumbhare, Daniel R Moore, Jenna B Gillen
{"title":"The influence of sex on fiber-specific indices of oxidative capacity in human skeletal muscle.","authors":"Celine Bailleul, Nathan Hodson, Sidney Abou Sawan, Dinesh Kumbhare, Daniel R Moore, Jenna B Gillen","doi":"10.1152/ajpregu.00298.2024","DOIUrl":"10.1152/ajpregu.00298.2024","url":null,"abstract":"<p><p>There are reports that females compared to males display increased skeletal muscle oxidative capacity in resting mixed-muscle fiber samples from the <i>vastus lateralis</i>, including markers of mitochondrial content and capillarization. Given that sex comparisons at the mixed-fiber level may be explained by differences in muscle fiber type between males and females, it remains unclear whether the oxidative capacity of type I and/or II fibers differs between sexes. The purpose of this study was to evaluate the influence of sex on fiber-specific indices of mitochondrial content and capillarization in healthy untrained males and females. Resting skeletal muscle samples from eumenorrheic females (<i>n</i> = 14; 23 ± 5 yr; 23.3 ± 3.2 kg/m<sup>2</sup>) and males (<i>n</i> = 13; 23 ± 4 yr; 23.1 ± 2.4 kg/m<sup>2</sup>) were analyzed via immunofluorescence staining. There were no sex differences in indices of capillarization (all <i>P</i> > 0.05) or mitochondrial content (all <i>P</i> > 0.05) in type I or type II muscle fibers. However, we observed lower capillary density in type II vs. type I muscle fibers in males (280 ± 66 vs. 364 ± 88 capillaries/mm<sup>2</sup>; <i>P</i> < 0.001) but not females (335 ± 77 vs. 329 ± 48 capillaries/mm<sup>2</sup>; <i>P</i> = 0.76), owing to greater cross-sectional area (CSA) of type II vs. type I fibers in males only (males <i>P</i> = 0.03; females <i>P</i> = 0.44). Females compared to males also displayed greater proportionate area of type I fibers (44 ± 12% vs. 31 ± 14%; <i>P</i> = 0.03) and smaller CSA of type IIx fibers (3,033 ± 902 vs. 5,573 ± 1,352 μm<sup>2</sup>; <i>P</i> = 0.002). Our results suggest that while muscle fiber type composition and size differ between males and females, there are no sex differences in mitochondrial content and capillarization of type I or II muscle fibers in untrained adults.<b>NEW & NOTEWORTHY</b> Research suggests that skeletal muscle oxidative capacity in mixed-fiber muscle homogenates is greater in females than in males. In healthy, untrained individuals, we demonstrate by fiber-specific immunofluorescence that females have a greater proportionate area of type I muscle fibers but no difference in mitochondrial content or capillarization of type I or II fibers compared to males. These findings suggest that although females display a more oxidative fiber type composition, sex does not influence muscle fiber-specific oxidative capacity.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R70-R80"},"PeriodicalIF":2.2,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144132105","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Isolating the effects of iterative cold exposure on metabolic heat production and hypothermia risk. 分离反复冷暴露对代谢产热和低温风险的影响。
IF 2.2 3区 医学
American journal of physiology. Regulatory, integrative and comparative physiology Pub Date : 2025-07-01 Epub Date: 2025-06-06 DOI: 10.1152/ajpregu.00095.2025
Billie K Alba, Afton D Seeley
{"title":"Isolating the effects of iterative cold exposure on metabolic heat production and hypothermia risk.","authors":"Billie K Alba, Afton D Seeley","doi":"10.1152/ajpregu.00095.2025","DOIUrl":"10.1152/ajpregu.00095.2025","url":null,"abstract":"","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R152-R153"},"PeriodicalIF":2.2,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144245913","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Is it the heat or the strain? Understanding risk and resilience in heat-exposed laborers. 是太热还是太紧张?了解热暴露工人的风险和恢复能力。
IF 2.2 3区 医学
American journal of physiology. Regulatory, integrative and comparative physiology Pub Date : 2025-07-01 Epub Date: 2025-06-18 DOI: 10.1152/ajpregu.00137.2025
Kevin O Murray, Orlando Laitano
{"title":"Is it the heat or the strain? Understanding risk and resilience in heat-exposed laborers.","authors":"Kevin O Murray, Orlando Laitano","doi":"10.1152/ajpregu.00137.2025","DOIUrl":"10.1152/ajpregu.00137.2025","url":null,"abstract":"","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R182-R183"},"PeriodicalIF":2.2,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144324177","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Is there a golden hour for exercise in aging females? A perspective on the female-specific effects of estradiol in regulating vascular endothelial function. 上了年纪的女性有锻炼的黄金时间吗?雌二醇在调节血管内皮功能中的女性特异性作用研究进展。
IF 2.2 3区 医学
American journal of physiology. Regulatory, integrative and comparative physiology Pub Date : 2025-07-01 Epub Date: 2025-05-17 DOI: 10.1152/ajpregu.00163.2024
Hollie Speer, Joseph M Northey
{"title":"Is there a golden hour for exercise in aging females? A perspective on the female-specific effects of estradiol in regulating vascular endothelial function.","authors":"Hollie Speer, Joseph M Northey","doi":"10.1152/ajpregu.00163.2024","DOIUrl":"10.1152/ajpregu.00163.2024","url":null,"abstract":"","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R225-R229"},"PeriodicalIF":2.2,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144085653","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A change in tone on the change in tone during exercise: the growing story of functional sympatholysis in humans. 运动中音调变化的音调变化:人类功能性交感神经溶解的发展历程。
IF 2.2 3区 医学
American journal of physiology. Regulatory, integrative and comparative physiology Pub Date : 2025-07-01 Epub Date: 2025-06-16 DOI: 10.1152/ajpregu.00143.2025
Brett S Kirby, Christopher M Hearon
{"title":"A change in tone on the change in tone during exercise: the growing story of functional sympatholysis in humans.","authors":"Brett S Kirby, Christopher M Hearon","doi":"10.1152/ajpregu.00143.2025","DOIUrl":"10.1152/ajpregu.00143.2025","url":null,"abstract":"","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R180-R181"},"PeriodicalIF":2.2,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144309364","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
SERCA activation prevents Ca2+ and ATP upregulation during 3-day soleus muscle unloading in rats. SERCA激活可阻止大鼠比目鱼肌卸除3天期间Ca2+和ATP的上调。
IF 2.2 3区 医学
American journal of physiology. Regulatory, integrative and comparative physiology Pub Date : 2025-07-01 Epub Date: 2025-05-28 DOI: 10.1152/ajpregu.00177.2024
Ksenia A Zaripova, Svetlana P Belova, Kristina A Sharlo, Darya A Sidorenko, Tatiana Y Kostrominova, Boris S Shenkman, Tatiana L Nemirovskaya
{"title":"SERCA activation prevents Ca<sup>2+</sup> and ATP upregulation during 3-day soleus muscle unloading in rats.","authors":"Ksenia A Zaripova, Svetlana P Belova, Kristina A Sharlo, Darya A Sidorenko, Tatiana Y Kostrominova, Boris S Shenkman, Tatiana L Nemirovskaya","doi":"10.1152/ajpregu.00177.2024","DOIUrl":"10.1152/ajpregu.00177.2024","url":null,"abstract":"<p><p>The imbalance in the ratio of protein synthesis versus protein degradation results in skeletal muscle atrophy following unloading. The onset of these processes is regulated by the sarcoplasmic concentrations of ATP and calcium (Ca<sup>2+</sup>). We tested the hypothesis that unloading-induced inactivation of sarcoendoplasmic reticulum calcium ATPase (SERCA) results in raised Ca<sup>2+</sup> concentrations, triggering catabolic processes. CDN1163, an activator of SERCA, was used to test this hypothesis. Three groups of male rats were used: control rats with intraperitoneal injection of placebo (C), 3 days of unloading with placebo injection (3HS), and 3 days of unloading injected with CDN1163 (3HSC). Treatment with CDN1163 during 3 days of soleus muscle unloading prevented the upregulation of Ca<sup>2+</sup> and ATP and the slow-to-fast shift in muscle fiber composition. This treatment blocked the decrease in the phosphorylation of the anabolic markers [glycogen synthase kinase-3β (GSK3β), eukaryotic translation elongation factor 2 (eEF2), and ribosomal protein S6 (S6, Ser240/244/Ser235/236)], and therefore it is likely that it improved the efficiency of translation in the unloaded muscle, but it did not affect mTORC1-dependent signaling. Treatment with CDN1163 also modulated the regulation of the Ca<sup>2+</sup>-dependent signaling in muscle during unloading via SERCA1 and calsequestrin 2 (CSQ2) and changes in the calcium/calmodulin-dependent protein kinase II (CaMKII) phosphorylation and the content of inositol 1,4,5-trisphosphate receptor (IP3R). In addition, CDN1163 prevented the upregulation of the mRNA expression of muscle-specific RING finger protein 1 (MuRF1) [but not ubiquitin ligase muscle atrophy F-box (MAFbx)] and attenuated the increase of casitas B lymphoma-b (Cbl-b) and ubiquitin mRNA expression during unloading. Activation of SERCA with CDN1163 prevents the upregulation of Ca<sup>2+</sup> and ATP, as well as calcium-dependent and ubiquitin-proteasome pathways markers, and improves protein translation efficiency in 3-day unloaded soleus muscle.<b>NEW & NOTEWORTHY</b> A hypothesis was tested that unloading-induced inactivation of SERCA results in the accumulation of increased Ca<sup>2+</sup> concentrations and activation of catabolic processes. CDN1163, an activator of SERCA, was used to test this hypothesis. CDN1163 prevented the decrease in phosphorylation of anabolic markers, which likely improved translation efficiency in unloaded muscle. CDN1163 prevented unloading-induced upregulation of mRNA expression of MuRF1 (but not MAFbx) and attenuated the increase of Cbl-b and ubiquitin mRNA expression.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R108-R122"},"PeriodicalIF":2.2,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144155466","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","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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