Acta Physiologica最新文献

{"title":"Respiratory and Metabolic Effects of Active Expiration in Freely Behaving Rats","authors":"Isabela P. Leirão,&nbsp;Pedro L. Katayama,&nbsp;Daniel B. Zoccal","doi":"10.1111/apha.70084","DOIUrl":"https://doi.org/10.1111/apha.70084","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Exposure to low oxygen (hypoxia) or high carbon dioxide levels (hypercapnia) leads to a compensatory increase in pulmonary ventilation. Among the motor changes supporting the respiratory responses is the recruitment of abdominal expiratory muscles (ABD), which can enhance expiratory airflow or alter the duration of the expiratory phase. In this study, we assessed the impact of ABD recruitment on metabolic, motor, and ventilatory parameters in unanesthetized, freely behaving animals.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Sprague–Dawley Holtzman male adult rats (<i>n</i> = 7) were instrumented to perform simultaneous recordings of pulmonary ventilation, body temperature, diaphragmatic and ABD activities, and O₂ consumption during exposure (20–30 min) to various levels of hypoxia (12%–8% O₂) and hypercapnia (3%–7% CO₂).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Hypoxia or hypercapnia exposure evoked active expiration (AE); however, ABD recruitment did not occur during the entire exposure period, displaying an intermittent profile. The occurrence of AE during hypoxia and hypercapnia conditions was linked to additional increases in tidal volume when compared to periods without ABD activity (<i>p</i> &lt; 0.05) and showed no associations with changes in diaphragmatic burst amplitude. Analyses of flow-like patterns suggested that AE during hypoxia recruited expiratory reserve volume during late expiration, while under hypercapnia, it accelerated lung emptying and increased the expiratory flow peak during post-inspiration. AE was also associated with increased oxygen consumption and did not improve air convection requirement.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>AE enhances pulmonary ventilation during hypoxia and hypercapnia primarily by increasing tidal volume. However, this motor behavior may also affect other mechanical aspects of the respiratory system to improve alveolar ventilation and gas exchange.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 9","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.70084","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144716640","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Absence of Parkin Results in Atrophy of Oxidative Myofibers and Modulation of AKT and MURF1 Signaling in Middle-Aged Male Mice","authors":"Isabela Aparecida Divino,&nbsp;Ana Laura da Vieira-da-Silva,&nbsp;Marcos Vinicius Esteca,&nbsp;Rafael Paschini Tonon,&nbsp;Felipe Oliveira Gomes da Cruz,&nbsp;Renata Rosseto Braga,&nbsp;Eduardo Rochete Ropelle,&nbsp;Paulo Guimarães Gandra,&nbsp;Igor Luchini Baptista","doi":"10.1111/apha.70082","DOIUrl":"https://doi.org/10.1111/apha.70082","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>This work aimed to investigate the effects of the loss of Parkin in middle-aged mice skeletal muscle, focusing on different types of myofibers and in the analysis of proteins related to protein synthesis and degradation as well as the analysis of force generation and motor balance.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We used male mice C57BL/6J (WT) and Parkin knockout mice, Parkintm1Shn (Parkin^−/−) at 3 and 10 months of age. We used Walking Beam, Open Field, Spider Mice and Maximum Power Tests to assess motor, balance, and endurance functions. We used flexor digitorum brevis (FDB) muscle for force generation analysis, and tibial anterior (TA) and soleus (SOL) muscles were used for biomolecular techniques because of their difference in fiber type. These muscles were used to investigate markers of protein synthesis and degradation, mitochondrial respiration, and myofiber diameter.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The Absence of Parkin in middle-aged mice leads to a reduction in isometric force generation but maintained overall motor and locomotion abilities, exhibited only minor balance deficits. In the SOL muscle of middle-aged Parkin^−/− mice, we observed a reduction of muscle mass and myofiber diameter, also a significant decrease in mitochondrial respiratory capacity and Complex V. In the same group, we observed a reduction in the phosphorylation of AKT and 4E-BP1, and an increase in <i>MURF-1</i> while Ubiquitin K63 levels decreased. We did not observe relevant differences in the TA muscle.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our results suggest middle-aged Parkin^−/− mice exhibited muscle atrophy and mitochondrial dysfunction primarily in oxidative myofibers before noticeable motor dysfunction occurs.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 9","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.70082","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144725616","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Life of a Kidney Podocyte","authors":"Desiree Loreth,&nbsp;Wiebke Sachs,&nbsp;Catherine Meyer-Schwesinger","doi":"10.1111/apha.70081","DOIUrl":"https://doi.org/10.1111/apha.70081","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Podocytes, highly specialized epithelial cells located in the glomerulus of the kidney, are essential to the filtration barrier that ensures separation of blood and urine. These cells exhibit a unique architecture, characterized by an intricate network of foot processes interconnected by slit diaphragms, which serve as a critical selective filter for plasma ultrafiltration.</p>\u0000 \u0000 <p>This review focusses on synthesizing current knowledge on podocyte physiology, emphasizing the roles of key proteins, signaling pathways, and environmental factors that influence their function.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Publications featuring current advances in molecular biology and imaging techniques were used to summarize new insights into the regulatory pathways governing podocyte homeostasis, as well as the mechanisms of injury and repair.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The biology of podocytes encompasses diverse processes, including cytoskeletal dynamics, cellular signaling, and interactions with neighboring cells and the extracellular matrix. Disruption of podocyte structure or function is fundamental to a variety of glomerular diseases, which can lead to proteinuria and progressive kidney failure.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Understanding the intricate mechanisms involved in maintaining podocyte homeostasis offers potential therapeutic strategies to protect and restore podocyte integrity, addressing a critical need in nephrology. By highlighting the intricate balance required for podocyte survival, we reinforce their significance as both a cornerstone of renal filtration and a focal point in kidney disease research.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 8","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.70081","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144681091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Skeletal Muscle Fatigue in Rats Is More Consistently Related to Increased Inorganic Phosphate Concentration Than Acidosis","authors":"Matthew T. Lewis,&nbsp;Fabio G. Laginestra,&nbsp;Jesse C. Craig,&nbsp;Markus Amann,&nbsp;Russell S. Richardson,&nbsp;Robert W. Wiseman,&nbsp;Ryan M. Broxterman","doi":"10.1111/apha.70083","DOIUrl":"https://doi.org/10.1111/apha.70083","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Distinguish the relative importance of intramuscular acidosis (hydrogen ion) and inorganic phosphate in skeletal muscle fatigue in vivo in rats.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We used direct sciatic nerve electrical stimulations to evoke twitches at different frequencies of contraction (0.25-, 0.50-, 0.75-, 1-, 2-, and 4-Hz) in the triceps surae to impose a range of intramuscular metabolic perturbations, quantified by phosphorus nuclear magnetic resonance spectroscopy. Linear mixed-effects models were used to analyze the relationships between peak twitch force and intramuscular hydrogen ion or inorganic phosphate concentration (as <i>Z</i>-scores) during the protocols that decreased peak twitch force (2- and 4-Hz).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Although intramuscular hydrogen ion and inorganic phosphate concentrations increased with increasing frequencies of contraction, peak twitch force did not begin to decrease until a “threshold” inorganic phosphate concentration was reached. A given hydrogen ion accumulation was associated with a greater decrease in peak twitch force during 4-Hz compared to 2-Hz (<i>β</i>: −1.19 vs. −0.62, <i>p</i> &lt; 0.001). In contrast, the decrease in peak twitch force for a given inorganic phosphate accumulation was not different between 4- and 2-Hz (<i>β</i>: −0.89 vs. −0.85, <i>p</i> = 0.889).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The inconsistent relationship between the decrease in twitch force and intramuscular hydrogen ion accumulation is not congruent with the primary mechanisms by which acidosis is thought to mediate muscle fatigue. In contrast, the discernible twitch force–inorganic phosphate breakpoint and the consistent relationship between the decrease in twitch force and intramuscular inorganic phosphate accumulation are congruent with the concept of a critical concentration beyond which inorganic phosphate mediates muscle fatigue.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 8","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.70083","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144666565","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Activation of the Carotid Sinus Nerve After Acute Myocardial Infarction in a Cardiorenal Syndrome Type 1 Model in Sprague–Dawley Rats","authors":"Rollssman de Oliveira Cavalheiro,&nbsp;Fernanda Brognara,&nbsp;Carlos Alberto Aguiar da Silva,&nbsp;Jaci Airton Castania,&nbsp;Carlos Augusto Fernandes Molina,&nbsp;David Murphy,&nbsp;Minna Moreira Dias Romano,&nbsp;Helio Cesar Salgado","doi":"10.1111/apha.70076","DOIUrl":"https://doi.org/10.1111/apha.70076","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>To evaluate the effect of carotid sinus nerve stimulation (CSNS) in the progression of cardiorenal syndrome type 1 (CRS1), 3 days after acute myocardial infarction (AMI).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Male rats were divided into four groups. CSNS was applied daily for 10 min over 3 days. Cardiac, renal, and inflammatory parameters characterized the CRS1 and the electroceutical effects of CSNS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>CSNS reduced the ischemic zone compared to the AMI group not exposed to CSNS (32.7% ± 2.2% vs. 8.0% ± 1.8%). Heart rate (bpm) was increased in the AMI group, showing 440 ± 7.6 at 48 h and 428 ± 1.0 at 60 h post-AMI. Additionally, arterial pressure (mmHg) was increased in the AMI group at 48 h, as follows: mean: 98 ± 1.7, diastolic: 89 ± 2.1, and systolic: 122 ± 5.3. In contrast, the CSNS + AMI group showed significant reductions of these parameters: mean: 79 ± 2.0, diastolic, 66 ± 1.7, and systolic: 99 ± 2.7. Renal injury was confirmed by increased apoptosis in the AMI group. A significant increase in TNF-α was observed in both heart and kidneys (pg/mg of tissue) in the AMI group and reduced IL-6 and IL-1β levels in the CSNS + AMI group, indicating an attenuation of the inflammatory responses by CSNS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This study demonstrates early cardiac and renal dysfunction in CRS1 following AMI, associated with elevated inflammatory markers (TNF-α, IL-6, and IL-1β) and renal apoptosis. Therefore, CSNS appears to be a promising electroceutical approach for CRS1. Besides, on the basis of previous studies from our laboratory, CSNS involves stimulation of the baroreflex, activating the parasympathetic and inhibiting the sympathetic nervous system.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 8","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144647126","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emerging Roles of Protein O-GlcNAcylation in Bone Remodeling: New Insights Into Osteoporosis","authors":"Jinpeng Wang,&nbsp;Site Xu,&nbsp;Yuchuan Xue,&nbsp;Kaicheng Wen,&nbsp;Mingzhe Sun,&nbsp;Lin Tao","doi":"10.1111/apha.70080","DOIUrl":"https://doi.org/10.1111/apha.70080","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Bone is a dynamic tissue undergoing constant remodeling mediated by osteoblasts and osteoclasts. An imbalance between these cells can lead to reduced bone mass, disrupted microarchitecture, and ultimately osteoporosis. O-GlcNAcylation is a dynamic and reversible posttranslational modification where uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) is added or removed from serine/threonine residues of proteins by OGT and OGA, respectively. Emerging evidence indicates that appropriate O-GlcNAcylation is essential for bone remodeling, although its specific effects remain controversial.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>This review aims to summarize the process of O-GlcNAcylation and critically evaluate its specific effects on osteoblast-mediated and osteoclast-mediated bone remodeling.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials &amp; Methods</h3>\u0000 \u0000 <p>Based on a comprehensive analysis of published scientific literature, we synthesized the current evidence regarding the role of O-GlcNAcylation in bone cell differentiation and function, and its association with osteoporosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Our analysis reveals that cellular demands for O-GlcNAcylation vary during osteoblastic and osteoclastic differentiation. Moderate O-GlcNAcylation is essential for osteoblast differentiation, whereas dynamic alterations in O-GlcNAcylation are crucial for osteoclast differentiation. Furthermore, elevated O-GlcNAcylation levels are consistently observed in both primary and secondary osteoporosis cases, suggesting a potential pathogenic role in the dysregulation of bone remodeling.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Discussion</h3>\u0000 \u0000 <p>These findings indicate that the effects of O-GlcNAcylation are cell type- and differentiation stage-dependent in bone. The observed elevation of O-GlcNAcylation in osteoporosis underscores its potential contribution to the dysregulation of bone remodeling pathways.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This review provides novel mechanistic insights into osteoporosis pathogenesis via dysregulation of the O-GlcNAcylation post-translational modification. Understanding these mechanisms will facilitate the development of novel therapeutic strategies targeting O-GlcNAcylation to restore balanced bone remodeling.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 8","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144635433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Christian Bohr. Discoverer of Homotropic and Heterotopic Allostery","authors":"Niels Bindslev","doi":"10.1111/apha.70016","DOIUrl":"https://doi.org/10.1111/apha.70016","url":null,"abstract":"<p>This essay recounts and revisits the scientific contributions of Christian Bohr, highlighting his pivotal role in discovering allostery about 120 years ago. Bohr's meticulous experimentation led to identifying two distinct forms of allostery: homotropic (single-ligand) and heterotropic (multi-ligand), the latter widely recognized as the Bohr Effect. His insights into oxygen binding to hemoglobin, as also modulated by carbon dioxide presence, laid the foundation for part of modern pharmacological advancements. Today, allosteric principles drive drug development, improving specificity and potentially minimizing adverse effects, with numerous allosteric modulators emerging in pharmaceutical pipelines. The treatise spans 13 chapters and an appendix with definitions on allosteric terms. It begins with Bohr's background, laboratory environment, and pivotal experiments in 1903 that demonstrated allosteric mechanisms. It traces Bohr's scientific journey—from medical training to his professorship in Copenhagen—and his collaborative research with Karl Hasselbalch and August Krogh. The work situates Bohr within the broader historical context, examining influence of earlier, 19th-century, and later physicochemical and physiological thoughts on his discoveries. Further chapters discuss dose-response relationships, including Hüfner's hyperbolic equation and Henri's enzyme kinetics, parallel to Bohr's findings. Bohr's S-shaped oxygen-hemoglobin binding curve, analyzed in 1904, marked a critical advancement in understanding homotropic allostery. Subsequent developments, such as Hill's equation and the Monod-Wyman-Changeux model, settled both types of allostery description. My study concludes with Bohr's abandonment in 1910 of his secretion theory and his legacy. Despite his early death in 1911, Bohr's contributions remain fundamental, warranting revitalized recognition for his discovery of allostery.</p>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 S734","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.70016","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144635511","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitochondrial Dysfunction and Defects in Mitochondrial Adaptation to Exercise Training in the Muscle of Patients With COPD: Disease Versus Disuse","authors":"Aldjia Abdellaoui,&nbsp;Farés Gouzi,&nbsp;Cécile Notarnicola,&nbsp;Annick Bourret,&nbsp;Amandine Suc,&nbsp;Dalila Laoudj-Chenivesse,&nbsp;Nelly Héraud,&nbsp;Jacques Mercier,&nbsp;Christian Préfaut,&nbsp;Maurice Hayot,&nbsp;Pascal Pomiès","doi":"10.1111/apha.70079","DOIUrl":"https://doi.org/10.1111/apha.70079","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Chronic obstructive pulmonary disease (COPD) is frequently associated with skeletal muscle dysfunction, having a considerable impact on exercise tolerance and patient prognosis. Mitochondria play a role in skeletal muscle weakness and exercise intolerance in COPD, but the majority of studies on mitochondrial function are biased by the fact that physical activity is greater in healthy subjects than in patients. Furthermore, exercise training (ET) has been proposed as a therapeutic strategy to prevent skeletal muscle dysfunction in COPD, but very few results are available on mitochondrial adaptation in response to ET.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Skeletal muscle mitochondrial function and the potential efficacy of ET on this function were compared between 12 patients with COPD and 21 healthy subjects with similar low levels of physical activity. Various markers of mitochondrial respiration, oxidative stress, biogenesis, and dynamics were assessed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Lower oxidative phosphorylation (OxPhos; <i>p</i> &lt; 0.001) and increased nonphosphorylating respiration (<i>p</i> = 0.025) and mitochondrial oxidative damage (lipid peroxidation (<i>p</i> = 0.014) and protein carbonylation (<i>p</i> = 0.020)) were observed in patients. While ET increased OxPhos efficiency (<i>p</i> = 0.011) and reduced nonphosphorylating respiration (<i>p</i> &lt; 0.001) and lipid peroxidation (<i>p</i> &lt; 0.001) in patients' muscle mitochondria, it fails to improve maximal respiration (<i>p</i> = 0.835) and expression of the antioxidant enzyme MnSOD (<i>p</i> = 0.606), mitochondrial transcription factor TFAM (<i>p</i> = 0.246), and mitochondrial complexes I, III, and IV (<i>p</i> = 0.816, <i>p</i> = 0.664, <i>p</i> = 0.888, respectively) as observed in healthy subjects.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The mitochondrial dysfunction and the defects in mitochondrial adaptation to ET that we observe in the muscle of patients with COPD are intrinsic to the disease and do not arise from muscle disuse.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 8","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.70079","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144589761","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Loss of Na+,HCO3−-Cotransporter NBCn1 Inhibits Net Acid Extrusion in the Atria and Causes Hypertension-Associated Cardiac Hypertrophy","authors":"María S. Espejo,&nbsp;Alejandro Orlowski,&nbsp;Trine M. Sørensen,&nbsp;Vladimir V. Matchkov,&nbsp;Ernesto A. Aiello,&nbsp;Ebbe Boedtkjer","doi":"10.1111/apha.70078","DOIUrl":"https://doi.org/10.1111/apha.70078","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Metabolic disturbances challenge pH homeostasis in cardiomyocytes. The electroneutral Na⁺,HCO₃⁻-cotransporter NBCn1/Slc4a7 mediates net acid extrusion, and genetic variation in <i>SLC4A7</i> contributes to human hypertension and cardiovascular risk. Nonetheless, the cardiac consequences of disrupted NBCn1 expression and function remain unclear. Here, we test the hypothesis that NBCn1, either directly or indirectly, influences cardiac structure, contractile function, and electrophysiological properties.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Based on mice with global loss of NBCn1, we measure intracellular pH in atria and ventricles of the heart (fluorescence microscopy), membrane potential responses (patch clamping), electro- and echocardiographic variables, blood pressure (telemetry), and cardiac dimensions (in vivo and postmortem analyses).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We find that protein and mRNA expression of NBCn1 are more prominent in atrial than in ventricular cardiomyocytes. Disruption of NBCn1 expression lowers Na⁺,HCO₃⁻-cotransport activity more than 50% in atria without significantly influencing net acid extrusion activity of ventricular cardiomyocytes. Loss of NBCn1 is associated with hypertension (blood pressure increased by ~15 mmHg), cardiac hypertrophy (heart/body weight increased by ~10%), and prolonged ventricular isovolumic relaxation time (increased by ~25%). NBCn1 knockout does not affect cardiomyocyte size, collagen content in the heart wall, overall cardiac contractile function, electrophysiological properties of ventricular cardiomyocytes, or the electrocardiogram.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>NBCn1 is a main mechanism of Na⁺,HCO₃⁻-cotransport in atrial tissue and contributes substantially to net acid extrusion during intracellular acidification. NBCn1 does not play any major direct role in ventricular cardiomyocytes of unchallenged mice, but global knockout of NBCn1 increases systemic blood pressure and results in the development of cardiac hypertrophy.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 8","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.70078","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144582211","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hypotaurine Reduces Glucose-Mediated Vascular Calcification","authors":"Marina A. Heuschkel,&nbsp;Armand Jaminon,&nbsp;Steffen Gräber,&nbsp;Anna Artati,&nbsp;Jerzy Adamski,&nbsp;Joachim Jankowski,&nbsp;Leon Schurgers,&nbsp;Nikolaus Marx,&nbsp;Willi Jahnen-Dechent,&nbsp;Claudia Goettsch","doi":"10.1111/apha.70075","DOIUrl":"https://doi.org/10.1111/apha.70075","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Vascular calcification (VC), a characteristic feature of peripheral artery disease in patients with diabetes and chronic kidney disease, has been associated with poor prognosis. We hypothesize that hyperglycemia drives VC through alterations in metabolomic and transcriptomic profiles.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Human coronary artery smooth muscle cells (SMCs) were cultured with 0, 5.5, and 25 mM glucose under calcifying conditions. Untargeted metabolomic and transcriptomic analyses were performed at different time points. Mitochondrial respiration was examined using Seahorse analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Glucose-treated SMCs promoted extracellular matrix (ECM) calcification in a concentration- and time-dependent manner. The absence of glucose entirely abolished SMC calcification but reduced SMC proliferation in control and calcifying conditions compared to 25 mM glucose. Multi-omics data integration revealed key players from the hypotaurine/taurine metabolic pathway as the center hub of the reconstructed network. Glucose promoted the hypotaurine secretion, while its intracellular abundance was not altered. Blocking hypotaurine production by propargylglycine increased ECM calcification, while hypotaurine treatment prevented it. Furthermore, omics data suggest energy remodeling in calcifying SMCs under hyperglycemia. Calcifying SMCs exhibited decreased oxygen consumption that was partially restored by hypotaurine. Validation of our in vitro models using the murine warfarin model demonstrated reduced hypotaurine/taurine transporter (TAUT) expression in SMCs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our multi-omics analysis revealed a role of the hypotaurine/taurine metabolic pathway in glucose-induced SMC calcification. Moreover, our data suggest a glucose-dependent energy remodeling in calcifying SMCs and that increasing glucose concentrations fuel ECM calcification. Our work highlights potential novel therapeutic targets that warrant further investigation in hyperglycemia-dependent in vitro SMC calcification.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 8","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.70075","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144573927","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}