Acta Physiologica最新文献

{"title":"Mobility, motion, and exercise","authors":"Pontus B. Persson, Anja Bondke Persson","doi":"10.1111/apha.14210","DOIUrl":"10.1111/apha.14210","url":null,"abstract":"<p>Sir Isaac Newton's 1686 “Philosophiae Naturalis Principia Mathematica”<span><sup>1</sup></span> has repeatedly, and notably by biomedical scientists, been cited as the most influential single piece of scientific writing ever produced<span><sup>2</sup></span>: Movement, the laws pertaining to which are laid down in this work, is a fundamental characteristic of life, and as such, essential for various biological functions. Thus, life scientists across disciplines study processes that involve changes in location, from a molecular level to that of groups of complex organisms.</p><p>Most complex organisms move from one place to another—in search for nutrition, new habitats, mates or to escape predators. Importantly, humans can convey complex information through speech, while animals must often also move their bodies to communicate. This is highly relevant for animal models with respect to translational physiology and has inspired numerous creative solutions by bioscientists to enable the study of, for example, the brain during movement.<span><sup>3</sup></span> Translational biomedical research—still so, and across disciplines—relies on animal models.<span><sup>4, 5</sup></span> When cognitive processes are studied, free movement is, despite the additional challenge of controlling or monitoring sensory input in a mobile subject, a prerequisite, as, for example, crucial behavioral patterns can only be observed and studied during free movement.<span><sup>3</sup></span> Nevertheless, telemetry-based studies in freely moving animals are extremely valuable for many more areas of application in physiology, for example in cardiovascular research,<span><sup>6</sup></span> studies of vegetative function and cardiovascular reflex responses<span><sup>7</sup></span> or renal function.<span><sup>8</sup></span> This is exemplified in recent studies: Wu et al. show the relevance of VIP+ miRNAs in sensory processing, olfactory neural activity, and “successful” olfactory function in rodents.<span><sup>9</sup></span> Toledo et al<span><sup>10</sup></span> did not primarily observe behavioral changes; however, the modulating effects of RVLM-C1 neurons on cardiorespiratory function at rest had never before studied in conscious, adult animals able to move freely, which adds great relevance to their results. As Pilowsky remarks, one crucial advantage of this study in awake animals, with reflexes intact, is the possibility to study changes in the sleep–wake cycle and normal breathing patterns, while, however, the effects of reflexes on the phenomena observed confounds the results and need to be taken into account critically.<span><sup>11</sup></span> Baseline heart rate recordings at rest in freely moving animals<span><sup>12</sup></span> are of particular value from a translational perspective, as they more closely resemble the natural situation.</p><p>At the cellular level, movement occurs during cell division, intracellular transport, and the functioning of immune cel","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"240 11","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.14210","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141858372","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":"Mitochondria can substitute for parvalbumin to lower cytosolic calcium levels in the murine fast skeletal muscle","authors":"Lorenzo Marcucci,&nbsp;Leonardo Nogara,&nbsp;Marta Canato,&nbsp;Elena Germinario,&nbsp;Anna Raffaello,&nbsp;Michela Carraro,&nbsp;Paolo Bernardi,&nbsp;Laura Pietrangelo,&nbsp;Simona Boncompagni,&nbsp;Feliciano Protasi,&nbsp;Nazareno Paolocci,&nbsp;Carlo Reggiani","doi":"10.1111/apha.14208","DOIUrl":"10.1111/apha.14208","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Parvalbumin (PV) is a primary calcium buffer in mouse fast skeletal muscle fibers. Previous work showed that PV ablation has a limited impact on cytosolic Ca²⁺ ([Ca²⁺]_cyto) transients and contractile response, while it enhances mitochondrial density and mitochondrial matrix-free calcium concentration ([Ca²⁺]_mito). Here, we aimed to quantitatively test the hypothesis that mitochondria act to compensate for PV deficiency.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We determined the free Ca²⁺ redistribution during a 2 s 60 Hz tetanic stimulation in the sarcoplasmic reticulum, cytosol, and mitochondria. Via a reaction–diffusion Ca²⁺ model, we quantitatively evaluated mitochondrial uptake and storage capacity requirements to compensate for PV lack and analyzed possible extracellular export.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>[Ca²⁺]_mito during tetanic stimulation is greater in knock-out (KO) (1362 ± 392 nM) than in wild-type (WT) (855 ± 392 nM), <i>p</i> &lt; 0.05. Under the assumption of a non-linear intramitochondrial buffering, the model predicts an accumulation of 725 μmoles/<i>L</i>\u0000 _fiber (buffering ratio 1:11 000) in KO, much higher than in WT (137 μmoles/<i>L</i>\u0000 _fiber, ratio 1:4500). The required transport rate via mitochondrial calcium uniporter (MCU) reaches 3 mM/s, compatible with available literature. TEM images of calcium entry units and Mn²⁺ quenching showed a greater capacity of store-operated calcium entry in KO compared to WT. However, levels of [Ca²⁺]_cyto during tetanic stimulation were not modulated to variations of extracellular calcium.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The model-based analysis of experimentally determined calcium distribution during tetanic stimulation showed that mitochondria can act as a buffer to compensate for the lack of PV. This result contributes to a better understanding of mitochondria's role in modulating [Ca²⁺]_cyto in skeletal muscle fibers.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"240 9","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.14208","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141791377","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":"Comparative functional analysis reveals differential nucleotide sensitivity between human and mouse UCP1","authors":"Eva Musiol,&nbsp;Tobias Fromme,&nbsp;Julia Hau,&nbsp;Antonella Di Pizio,&nbsp;Martin Klingenspor","doi":"10.1111/apha.14209","DOIUrl":"10.1111/apha.14209","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Mitochondrial uncoupling protein 1 (UCP1) is a unique protein of brown adipose tissue. Upon activation by free fatty acids, UCP1 facilitates a thermogenic net proton flux across the mitochondrial inner membrane. Non-complexed purine nucleotides inhibit this fatty acid-induced activity of UCP1. The most available data have been generated from rodent model systems. In light of its role as a putative pharmacological target for treating metabolic disease, in-depth analyses of human UCP1 activity, regulation, and structural features are essential.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In the present study, we established a doxycycline-regulated cell model with inducible human or murine UCP1 expression and conducted functional studies using respirometry comparing wild-type and mutant variants of human UCP1.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We demonstrate that human and mouse UCP1 exhibit similar specific fatty acid-induced activity but a different inhibitory potential of purine nucleotides. Mutagenesis of non-conserved residues in human UCP1 revealed structural components in α-helix 56 and α-helix 6 crucial for uncoupling function.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Comparative studies of human UCP1 with other orthologs can provide new insights into the structure–function relationship for this mitochondrial carrier and will be instrumental in searching for new activators.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"240 9","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.14209","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141786470","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":"MicroRNA-210 mediates hypoxia-induced pulmonary hypertension by targeting mitochondrial bioenergetics and mtROS flux","authors":"Abu Shufian Ishtiaq Ahmed,&nbsp;Arlin B. Blood,&nbsp;Lubo Zhang","doi":"10.1111/apha.14212","DOIUrl":"10.1111/apha.14212","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Chronic hypoxia is a common cause of pulmonary hypertension (PH). We test the hypothesis that microRNA-210 (miR-210) mediates hypoxia-induced PH by targeting mitochondrial metabolism and increasing reactive oxygen species (mtROS) production in the lungs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Adult wildtype (WT) or miR-210 knockout (KO) mice were exposed to hypoxia (10.5% O₂) or normoxia for 4 weeks. We measured miR-210 levels, right ventricular systolic pressure (RVSP), and histological changes in heart and lung tissues. Mitochondrial bioenergetics and mtROS production were assessed in isolated lung mitochondria.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Hypoxia increased right ventricular wall thickness and pulmonary vessel wall muscularization in WT, but not miR-210 KO mice. No sex differences were observed. In male mice, hypoxia increased miR-210 levels in the lung and RVSP, which were abrogated by miR-210 deficiency. Hypoxia upregulated mitochondrial oxygen consumption rate and mtROS flux, which were negated in miR-210 KO animals. In addition, chronic hypoxia increased macrophage accumulation in lungs of WT, but not miR-210 KO mice. Moreover, miR-210 overexpression in lungs of WT animals recapitulated the effects of hypoxia and increased mitochondrial oxygen consumption rate, mtROS flux, right ventricular wall thickness, pulmonary vessel wall muscularization and RVSP. MitoQ revoked the effects of miR-210 on lung mitochondrial bioenergetics, right ventricular and pulmonary vessel remodeling and RVSP.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our findings with loss-of-function and gain-of-function approaches provide explicit evidence that miR-210 mediates hypoxia-induced PH by upregulating mitochondrial bioenergetics and mtROS production in a murine model, revealing new insights into the mechanisms and therapeutic targets for treatment of PH.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"240 9","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141786507","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":"Irisin preserves mitochondrial integrity and function in tubular epithelial cells after ischemia–reperfusion-induced acute kidney injury","authors":"Yu Cui,&nbsp;Lu Yu,&nbsp;Wenqi Cong,&nbsp;Shan Jiang,&nbsp;Xingyu Qiu,&nbsp;Chunchun Wei,&nbsp;Gui Zheng,&nbsp;Jianhua Mao,&nbsp;Ruisheng Liu,&nbsp;Andreas Patzak,&nbsp;Pontus B. Persson,&nbsp;Jianghua Chen,&nbsp;Liang Zhao,&nbsp;En Yin Lai","doi":"10.1111/apha.14211","DOIUrl":"10.1111/apha.14211","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>A myokine secreted by skeletal muscles during exercise called irisin mitigates ischemia–reperfusion (I/R) injury in epithelial cells of various organs by limiting damage to mitochondria. We test whether irisin may preserve the mitochondrial integrity and function in renal tubular epithelial cells and protect against ischemia–reperfusion-induced acute kidney injury (AKI).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We correlated serum irisin levels with serum creatinine and BUN levels from both AKI patients and healthy individuals. In mice with irisin administration, various renal injury markers such as serum creatinine, BUN, kidney injury molecule-1 (Kim-1), and neutrophil gelatinase-associated lipocalin (NGAL), and renal histopathology were assessed after I/R. To identify the potential mechanisms of the protective of irisin's protective effect, we perfused proximal tubules under confocal microscopy and analyzed kidney tissues by qPCR, western blot, and immunohistochemistry.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Serum irisin correlated inversely with serum creatinine and BUN levels were significantly lower in AKI patients than in healthy subjects. Administering irisin to mice after I/R decreased biomarker levels for AKI including serum creatinine, BUN, Kim-1, NAGL and lessened histological changes. In kidney tissues of mice, irisin upregulated the mitochondrial autophagy marker protein microtubule-associated protein 1 light chain 3 (LC3), the mitochondrial autophagy pathway-related proteins PTEN-induced putative kinase 1 (PINK1) and Parkinson's disease 2 parkin (PARK2) and downregulated the reactive substrate protein sequestosome 1 (P62) and mitochondrial membrane proteins translocase of outer mitochondrial membrane 20 (TOM20) and translocase of inner mitochondrial membrane 23 (TIM23).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Irisin protects against renal I/R injury, which may involve the preservation of mitochondrial integrity and function.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"240 9","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.14211","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141786506","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":"Plasma concentrations of peptide hormones: Unrealistic levels of vasopressin (AVP), oxytocin (OXT), and brain natriuretic peptide (BNP)","authors":"Peter Bie","doi":"10.1111/apha.14200","DOIUrl":"10.1111/apha.14200","url":null,"abstract":"<p>Hormones are specific molecules measured in biological fluids by elaborate analytical systems requiring meticulous attention. Variation between laboratories can be expected. However, recently published measurements of AVP, OXT, and BNP in human plasma under basal/control conditions include numbers which, between publications, vary by 100–10 000-fold. Generally, the methods descriptions are scant, at best, and provide no information about quality control measures. Clearly, two results describing the same basal hormone concentration by numbers three orders of magnitude apart are incongruent providing reason for concern. Basal concentrations of bioactive AVP, OXT, and BNP in human plasma are in the order of 1–10 pmol/L. Therefore, assay systems applied to plasma must be able to measure concentrations of less than 1 pmol/L with appropriate specificity and accuracy. Basal concentrations of AVP, OXT, and BNP above 100 pmol/L should be reconsidered, as such results do not reflect bioactive hormone levels in humans, rats, or mice. Any concentration above 1000 pmol/L is of concern because such levels of bioactive hormone may be seen only under extreme conditions, if at all.</p>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"240 9","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.14200","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141732905","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":"Soluble adenylyl cyclase is an acid-base sensor in rainbow trout red blood cells that regulates intracellular pH and haemoglobin–oxygen binding","authors":"Till S. Harter,&nbsp;Emma A. Smith,&nbsp;Cristina Salmerón,&nbsp;Angus B. Thies,&nbsp;Bryan Delgado,&nbsp;Rod W. Wilson,&nbsp;Martin Tresguerres","doi":"10.1111/apha.14205","DOIUrl":"10.1111/apha.14205","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>To identify the physiological role of the acid-base sensing enzyme, soluble adenylyl cyclase (sAC), in red blood cells (RBC) of the model teleost fish, rainbow trout.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We used: (i) super-resolution microscopy to determine the subcellular location of sAC protein; (ii) live-cell imaging of RBC intracellular pH (pH_i) with specific sAC inhibition (KH7 or LRE1) to determine its role in cellular acid-base regulation; (iii) spectrophotometric measurements of haemoglobin–oxygen (Hb-O₂) binding in steady-state conditions; and (iv) during simulated arterial-venous transit, to determine the role of sAC in systemic O₂ transport.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Distinct pools of sAC protein were detected in the RBC cytoplasm, at the plasma membrane and within the nucleus. Inhibition of sAC decreased the setpoint for RBC pH_i regulation by ~0.25 pH units compared to controls, and slowed the rates of RBC pH_i recovery after an acid-base disturbance. RBC pH_i recovery was entirely through the anion exchanger (AE) that was in part regulated by HCO₃⁻-dependent sAC signaling. Inhibition of sAC decreased Hb-O₂ affinity during a respiratory acidosis compared to controls and reduced the cooperativity of O₂ binding. During in vitro simulations of arterial-venous transit, sAC inhibition decreased the amount of O₂ that is unloaded by ~11%.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>sAC represents a novel acid-base sensor in the RBCs of rainbow trout, where it participates in the modulation of RBC pH_i and blood O₂ transport though the regulation of AE activity. If substantiated in other species, these findings may have broad implications for our understanding of cardiovascular physiology in vertebrates.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"240 10","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.14205","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141730786","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":"A single bout of resistance exercise triggers mitophagy, potentially involving the ejection of mitochondria in human skeletal muscle","authors":"Francisco Díaz-Castro,&nbsp;Mauro Tuñón-Suárez,&nbsp;Patricia Rivera,&nbsp;Javier Botella,&nbsp;Jorge Cancino,&nbsp;Ana María Figueroa,&nbsp;Juan Gutiérrez,&nbsp;Claudette Cantin,&nbsp;Louise Deldicque,&nbsp;Hermann Zbinden-Foncea,&nbsp;Joachim Nielsen,&nbsp;Carlos Henríquez-Olguín,&nbsp;Eugenia Morselli,&nbsp;Mauricio Castro-Sepúlveda","doi":"10.1111/apha.14203","DOIUrl":"10.1111/apha.14203","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>The present study aimed to investigate the effects of a single bout of resistance exercise on mitophagy in human skeletal muscle (SkM).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Eight healthy men were recruited to complete an acute bout of one-leg resistance exercise. SkM biopsies were obtained one hour after exercise in the resting leg (Rest-leg) and the contracting leg (Ex-leg). Mitophagy was assessed using protein-related abundance, transmission electron microscopy (TEM), and fluorescence microscopy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Our results show that acute resistance exercise increased pro-fission protein phosphorylation (DRP1^Ser616) and decreased mitophagy markers such as PARKIN and BNIP3L/NIX protein abundance in the Ex-leg. Additionally, mitochondrial complex IV decreased in the Ex-leg when compared to the Rest-leg. In the Ex-leg, TEM and immunofluorescence images showed mitochondrial cristae abnormalities, a mitochondrial fission phenotype, and increased mitophagosome-like structures in both subsarcolemmal and intermyofibrillar mitochondria. We also observed increased mitophagosome-like structures on the subsarcolemmal cleft and mitochondria in the extracellular space of SkM in the Ex-leg. We stimulated human primary myotubes with CCCP, which mimics mitophagy induction in the Ex-leg, and found that BNIP3L/NIX protein abundance decreased independently of lysosomal degradation. Finally, in another human cohort, we found a negative association between BNIP3L/NIX protein abundance with both mitophagosome-like structures and mitochondrial cristae density in the SkM.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The findings suggest that a single bout of resistance exercise can initiate mitophagy, potentially involving mitochondrial ejection, in human skeletal muscle. BNIP3L/NIX is proposed as a sensitive marker for assessing mitophagy flux in SkM.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"240 9","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141632036","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":"HIF-1α limits myocardial infarction by promoting mitophagy in mouse hearts adapted to chronic hypoxia","authors":"Petra Alanova,&nbsp;Lukas Alan,&nbsp;Barbora Opletalova,&nbsp;Romana Bohuslavova,&nbsp;Pavel Abaffy,&nbsp;Katerina Matejkova,&nbsp;Kristyna Holzerova,&nbsp;Daniel Benak,&nbsp;Nina Kaludercic,&nbsp;Roberta Menabo,&nbsp;Fabio Di Lisa,&nbsp;Bohuslav Ostadal,&nbsp;Frantisek Kolar,&nbsp;Gabriela Pavlinkova","doi":"10.1111/apha.14202","DOIUrl":"10.1111/apha.14202","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>The transcriptional factor HIF-1α is recognized for its contribution to cardioprotection against acute ischemia/reperfusion injury. Adaptation to chronic hypoxia (CH) is known to stabilize HIF-1α and increase myocardial ischemic tolerance. However, the precise role of HIF-1α in mediating the protective effect remains incompletely understood.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Male wild-type (WT) mice and mice with partial <i>Hif1a</i> deficiency (<i>hif1a</i>\u0000 ^+/−) were exposed to CH for 4 weeks, while their respective controls were kept under normoxic conditions. Subsequently, their isolated perfused hearts were subjected to ischemia/reperfusion to determine infarct size, while RNA-sequencing of isolated cardiomyocytes was performed. Mitochondrial respiration was measured to evaluate mitochondrial function, and western blots were performed to assess mitophagy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We demonstrated enhanced ischemic tolerance in WT mice induced by adaptation to CH compared with their normoxic controls and chronically hypoxic <i>hif1a</i>\u0000 ^+/− mice. Through cardiomyocyte bulk mRNA sequencing analysis, we unveiled significant reprogramming of cardiomyocytes induced by CH emphasizing mitochondrial processes. CH reduced mitochondrial content and respiration and altered mitochondrial ultrastructure. Notably, the reduced mitochondrial content correlated with enhanced autophagosome formation exclusively in chronically hypoxic WT mice, supported by an increase in the LC3-II/LC3-I ratio, expression of PINK1, and degradation of SQSTM1/p62. Furthermore, pretreatment with the mitochondrial division inhibitor (mdivi-1) abolished the infarct size-limiting effect of CH in WT mice, highlighting the key role of mitophagy in CH-induced cardioprotection.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>These findings provide new insights into the contribution of HIF-1α to cardiomyocyte survival during acute ischemia/reperfusion injury by activating the selective autophagy pathway.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"240 9","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.14202","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141625376","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":"Increased water intake dilutes protective uromodulin levels in urine and results in increased rates of pyelonephritis in a murine model","authors":"Aimi D. K. Hamilton,&nbsp;Laura V. Sparsoe,&nbsp;Mathias Skov,&nbsp;Nanna Johnsen,&nbsp;Mette H. Chreistensen,&nbsp;Thomas J. Corydon,&nbsp;Helle Praetorius","doi":"10.1111/apha.14204","DOIUrl":"10.1111/apha.14204","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Urinary tract infections (UTIs) rank among the most prevalent infections in humans, carrying substantial implications for public health. Women experiencing recurrent UTIs are often advised to boost their fluid intake to help eliminate bacteria. In this study, we explored the impact of elevated fluid consumption during UTIs using a mouse model of pyelonephritis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>UTI was induced in 8–10 w female BALB/cJ-mice by surgically injecting <i>Escherichia coli</i> (O6:K13:H1) into the bladder whereafter mice were randomized to gel food (GF) or regular chow. Immune response and infection severity were determined 24-h post-infection. In vitro bacterial growth (OD₆₀₀) was determined in urine from mice or from human volunteers.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Gel feeding increased urine output (1.40 ± 0.77 μL min⁻¹, <i>p</i> &lt; 0.01) and diluted the urine (668.7 ± 177 mOsmol kg⁻¹, <i>p</i> &lt; 0.0001) compared to controls on regular chow (urine output: 0.34 ± 0.27 μL min⁻¹, osmolality: 1439 ± 473.5 mOsmol kg⁻¹). Mice on GF had a higher risk of pyelonephritis (87.5%) and more severe infections (26.22 ± 9.88 CFU mg⁻¹ tissue) compared to controls (43.75%; 3.87 ± 3.56 CFU mg⁻¹, <i>p</i> &lt; 0.01). Correspondingly, the growth <i>of E. coli</i> was markedly reduced at osmolalities above 1200 mOsmol kg⁻¹ compared to 600 mOsmol kg⁻¹ and GF mice had lower urine levels of uromodulin (13.70 ± 1.89 μg mL⁻¹, <i>p</i> &lt; 0.01) compared to controls (24.65 ± 2.70 μg mL⁻¹).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Increased water intake and urine flow in mice will markedly increase the risk of pyelonephritis. The increased risk may reflect reduced urine uromodulin combined with optimized growth conditions for <i>E. coli</i>. The study does not immediately support the notion that established UTIs can be eliminated by increased water intake.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"240 9","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.14204","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141615349","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}