Acta Physiologica最新文献

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Correction to “Beneficial effects of MGL-3196 and BAM15 combination in a mouse model of fatty liver disease” 更正 "MGL-3196 和 BAM15 联合疗法在脂肪肝小鼠模型中的益处"。
IF 5.6 2区 医学
Acta Physiologica Pub Date : 2024-11-12 DOI: 10.1111/apha.14250
{"title":"Correction to “Beneficial effects of MGL-3196 and BAM15 combination in a mouse model of fatty liver disease”","authors":"","doi":"10.1111/apha.14250","DOIUrl":"10.1111/apha.14250","url":null,"abstract":"<p>Zhou, M., Li, C., Byrne, F. L., Vancuylenburg, C. S., Olzomer, E. M., Hargreaves, A., Wu, L. E., Shackel, N. A., Santos, W. L., &amp; Hoehn, K. L. Beneficial effects of MGL-3196 and BAM15 combination in a mouse model of fatty liver disease. <i>Acta Physiologica</i>. 2014; 240(10): e14217. https://doi.org/10.1111/apha.14217</p><p>In Figure 1A, the compound structure of MGL-3196 is incorrect due to an extra bond between the Cl and N. The corrected structure (below) has the bond between the Cl and N removed.</p>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.14250","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142612905","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}
引用次数: 0
Impaired suppression of fatty acid release by insulin is a strong predictor of reduced whole-body insulin-mediated glucose uptake and skeletal muscle insulin receptor activation 胰岛素对脂肪酸释放的抑制作用受损是全身胰岛素介导的葡萄糖摄取和骨骼肌胰岛素受体活化减少的一个有力预测因素。
IF 5.6 2区 医学
Acta Physiologica Pub Date : 2024-11-01 DOI: 10.1111/apha.14249
Michael W. Schleh, Benjamin J. Ryan, Cheehoon Ahn, Alison C. Ludzki, Douglas W. Van Pelt, Lisa M. Pitchford, Olivia K. Chugh, Austin T. Luker, Kathryn E. Luker, Dmitri Samovski, Nada A. Abumrad, Charles F. Burant, Jeffrey F. Horowitz
{"title":"Impaired suppression of fatty acid release by insulin is a strong predictor of reduced whole-body insulin-mediated glucose uptake and skeletal muscle insulin receptor activation","authors":"Michael W. Schleh,&nbsp;Benjamin J. Ryan,&nbsp;Cheehoon Ahn,&nbsp;Alison C. Ludzki,&nbsp;Douglas W. Van Pelt,&nbsp;Lisa M. Pitchford,&nbsp;Olivia K. Chugh,&nbsp;Austin T. Luker,&nbsp;Kathryn E. Luker,&nbsp;Dmitri Samovski,&nbsp;Nada A. Abumrad,&nbsp;Charles F. Burant,&nbsp;Jeffrey F. Horowitz","doi":"10.1111/apha.14249","DOIUrl":"10.1111/apha.14249","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>To examine factors underlying why most, but not all, adults with obesity exhibit impaired insulin-mediated glucose uptake, we compared: (1) adipose tissue fatty acid (FA) release, (2) skeletal muscle lipid droplet (LD) characteristics, and (3) insulin signalling events, in skeletal muscle of adults with obesity with relatively high versus low insulin-mediated glucose uptake.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Seventeen adults with obesity (BMI: 36 ± 3 kg/m<sup>2</sup>) completed a 2 h hyperinsulinemic–euglycemic clamp with stable isotope tracer infusions to measure glucose rate of disappearance (glucose Rd) and FA rate of appearance (FA Ra). Skeletal muscle biopsies were collected at baseline and 30 min into the insulin infusion. Participants were stratified into HIGH (<i>n</i> = 7) and LOW (<i>n</i> = 10) insulin sensitivity cohorts by their glucose Rd during the hyperinsulinemic clamp (LOW&lt; 400; HIGH &gt;550 nmol/kgFFM/min/[μU/mL]).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Insulin-mediated suppression of FA Ra was lower in LOW compared with HIGH (<i>p</i> &lt; 0.01). In skeletal muscle, total intramyocellular lipid content did not differ between cohorts. However, the size of LDs in the subsarcolemmal region (SS) of type II muscle fibres was larger in LOW compared with HIGH (<i>p</i> = 0.01). Additionally, insulin receptor-β (IRβ) interactions with regulatory proteins CD36 and Fyn were lower in LOW versus HIGH (<i>p</i> &lt; 0.01), which aligned with attenuated insulin-mediated Tyr phosphorylation of IRβ and downstream insulin-signalling proteins in LOW.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Collectively, reduced ability for insulin to suppress FA mobilization, with accompanying modifications in intramyocellular LD size and distribution, and diminished IRβ interaction with key regulatory proteins may be key contributors to impaired insulin-mediated glucose uptake commonly found in adults with obesity.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11674998/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142563544","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}
引用次数: 0
Differential production of mitochondrial reactive oxygen species between mouse (Mus musculus) and crucian carp (Carassius carassius) 小鼠(Mus musculus)和鲫鱼(Carassius carassius)线粒体活性氧产生的差异。
IF 5.6 2区 医学
Acta Physiologica Pub Date : 2024-10-28 DOI: 10.1111/apha.14244
Lucie Gerber, May-Kristin Torp, Göran E. Nilsson, Sjannie Lefevre, Kåre-Olav Stensløkken
{"title":"Differential production of mitochondrial reactive oxygen species between mouse (Mus musculus) and crucian carp (Carassius carassius)","authors":"Lucie Gerber,&nbsp;May-Kristin Torp,&nbsp;Göran E. Nilsson,&nbsp;Sjannie Lefevre,&nbsp;Kåre-Olav Stensløkken","doi":"10.1111/apha.14244","DOIUrl":"10.1111/apha.14244","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>In most vertebrates, oxygen deprivation and subsequent re-oxygenation are associated with mitochondrial impairment and excess production of reactive oxygen species (ROS) like hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>). This in turn triggers a cascade of cell-damaging events in a temperature-dependent manner. The crucian carp (<i>Carassius carassius</i>) is one of few vertebrates that survives months without oxygen at cold temperatures and overcomes oxidative damage during re-oxygenation periods. Mitochondria of this anoxia-tolerant species therefore serve as an excellent model in translational research to study adaptation and resilience to low oxygen conditions and thermal variability.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Here, we used high-resolution respirometry on isolated mitochondria from hearts of crucian carp and the anoxia-intolerant mouse (<i>Mus musculus</i>), at 37 and 8°C; two temperatures relevant for transplantation medicine (i.e., graft preservation and subsequent rewarming).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We find: (1) a striking difference in H<sub>2</sub>O<sub>2</sub> release between the two species at 37°C despite comparable mitochondrial efficiency and capacity, (2) a massive H<sub>2</sub>O<sub>2</sub> release after inhibition of complex V in mouse at 37°C that is absent in crucian carp, and prevented in mouse by incubation at 8°C or uncoupling with a protonophore at 37°C, and (3) indications that differences in mitochondrial complex I and II capacity and thermal sensitivity influence the release of mitochondrial H<sub>2</sub>O<sub>2</sub> relative to respiration.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our findings provide comparative insights into a spectrum of mitochondrial adaptations in vertebrates and the importance of thermal variability. Furthermore, the species- and temperature-related changes associated with mitochondria highlighted in this study may help identify mitochondria-based targets for translational medicine.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"240 12","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.14244","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142491349","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}
引用次数: 0
A quantitative analysis of bestrophin 1 cellular localization in mouse cerebral cortex 小鼠大脑皮层中 bestrophin 1 细胞定位的定量分析
IF 5.6 2区 医学
Acta Physiologica Pub Date : 2024-10-28 DOI: 10.1111/apha.14245
Michael Di Palma, Wuhyun Koh, C. Justin Lee, Fiorenzo Conti
{"title":"A quantitative analysis of bestrophin 1 cellular localization in mouse cerebral cortex","authors":"Michael Di Palma,&nbsp;Wuhyun Koh,&nbsp;C. Justin Lee,&nbsp;Fiorenzo Conti","doi":"10.1111/apha.14245","DOIUrl":"10.1111/apha.14245","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Calcium-activated ligand-gated chloride channels, beyond their role in maintaining anion homeostasis, modulate neuronal excitability by facilitating nonvesicular neurotransmitter release. BEST1, a key member of this family, is permeable to γ-aminobutyric acid (GABA) and glutamate. While astrocytic BEST1 is well-studied and known to regulate neurotransmitter levels, its distribution and role in other brain cell types remain unclear. This study aimed to reassess the localization of BEST1 in the mouse cerebral cortex.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We examined the localization and distribution of BEST1 in the mouse parietal cortex using light microscopy, confocal double-labeling with markers for astrocytes, neurons, microglia, and oligodendrocyte precursor cells, and 3D reconstruction techniques.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In the cerebral cortex, BEST1 is more broadly distributed than previously thought. Neurons are the second most abundant BEST1<sup>+</sup> cell type in the cerebral cortex, following astrocytes. BEST1 is diffusely expressed in neuronal somatic and neuropilar domains and is present at glutamatergic and GABAergic terminals, with a prevalence at GABAergic terminals. We also confirmed that BEST1 is expressed in cortical microglia and identified it in oligodendrocyte precursor cells, albeit to a lesser extent.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Together, these findings suggest that BEST1's role in controlling neurotransmission may extend beyond astrocytes to include other brain cells. Understanding BEST1's function in these cells could offer new insights into the molecular mechanisms shaping cortical circuitry. Further research is needed to clarify the diverse roles of BEST1 in both normal and pathophysiological conditions.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11674994/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142520406","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}
引用次数: 0
Calcineurin inhibitors and the renin–angiotensin–aldosterone system 降钙素抑制剂和肾素-血管紧张素-醛固酮系统。
IF 5.6 2区 医学
Acta Physiologica Pub Date : 2024-10-25 DOI: 10.1111/apha.14248
Mesut Berber, David Penton
{"title":"Calcineurin inhibitors and the renin–angiotensin–aldosterone system","authors":"Mesut Berber,&nbsp;David Penton","doi":"10.1111/apha.14248","DOIUrl":"10.1111/apha.14248","url":null,"abstract":"<p>Calcineurin inhibitors (CnIs) are effective immunosuppressants with decades of accumulated experience in treating immune disorders and, most notably, solid organ transplantation. While CnIs have significantly increased graft survival and transformed the patient standard of care, their use has been overshadowed by a number of undesired side effects. For instance, CnI-associated nephrotoxicity has been reported since early studies and remains a major therapeutic concern. The occurrence of several ion imbalances alongside hypertension was also noted early on, indicating the involvement of the renin–angiotensin–aldosterone system (RAAS) in CnI-mediated toxicity. However, the literature in this field is crowded with conflicting reports from clinical trials as well as studies using animal and invitro models. With this review, we aim to provide a structured and updated overview of the physiological and pathophysiological evidence supporting the involvement of the classical RAAS in CnI-associated toxicity.</p>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"240 12","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.14248","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142491348","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}
引用次数: 0
High chloride induces aldosterone resistance in the distal nephron 高氯化物诱导远端肾小球的醛固酮抵抗。
IF 5.6 2区 医学
Acta Physiologica Pub Date : 2024-10-24 DOI: 10.1111/apha.14246
Helga Vitzthum, Nina Hauswald, Helena Pham, Leya Eckermann-Reimer, Catherine Meyer-Schwesinger, Heimo Ehmke
{"title":"High chloride induces aldosterone resistance in the distal nephron","authors":"Helga Vitzthum,&nbsp;Nina Hauswald,&nbsp;Helena Pham,&nbsp;Leya Eckermann-Reimer,&nbsp;Catherine Meyer-Schwesinger,&nbsp;Heimo Ehmke","doi":"10.1111/apha.14246","DOIUrl":"10.1111/apha.14246","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Increasing the dietary intake of K<sup>+</sup> in the setting of a high salt intake promotes renal Na<sup>+</sup> excretion even though K<sup>+</sup> concurrently enhances the secretion of aldosterone, the most effective stimulus for renal Na<sup>+</sup> reabsorption. Here, we questioned whether in the high salt state a mechanism exists, which attenuates the aldosterone response to prevent renal Na<sup>+</sup> reabsorption after high K<sup>+</sup> intake.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Mice were fed diets containing varying amounts of Na<sup>+</sup> combined with KCl or KCitrate. Murine cortical connecting duct (mCCDcl1) cells were cultured in media containing normal or high [Cl<sup>−</sup>]. The response to aldosterone was analyzed by high-resolution imaging and by biochemical approaches.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The canonical cellular response to aldosterone, encompassing translocation of the mineralocorticoid receptor (MR) and activation of the epithelial Na<sup>+</sup> channel ENaC was repressed in Na<sup>+</sup>-replete mice fed a high KCl diet, even though plasma aldosterone concentrations were increased. The response to aldosterone was restored in Na<sup>+</sup>-replete mice when the extracellular [Cl<sup>−</sup>] increase was prevented by feeding a high KCitrate diet. In mCCDcl1 cells, an elevated extracellular [Cl<sup>−</sup>] was sufficient to disrupt the aldosterone-induced MR translocation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>These findings indicate a pivotal role for extracellular [Cl<sup>−</sup>] in modulating renal aldosterone signaling to adapt MR activation by a high K<sup>+</sup> intake to the NaCl balance. An impairment of [Cl<sup>−</sup>]-mediated aldosterone resistance may contribute to excessive MR activation by aldosterone in the presence of a high salt intake characteristic of the Western diet, resulting in an inappropriate salt reabsorption and its downstream detrimental effects.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11674995/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142491350","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}
引用次数: 0
The effects of cannabinoids on the kidney 大麻素对肾脏的影响。
IF 5.6 2区 医学
Acta Physiologica Pub Date : 2024-10-24 DOI: 10.1111/apha.14247
Steven Didik, Oleg Palygin, Mark Chandy, Alexander Staruschenko
{"title":"The effects of cannabinoids on the kidney","authors":"Steven Didik,&nbsp;Oleg Palygin,&nbsp;Mark Chandy,&nbsp;Alexander Staruschenko","doi":"10.1111/apha.14247","DOIUrl":"10.1111/apha.14247","url":null,"abstract":"<p>Cannabinoids are a class of drugs derived from the <i>Cannabis</i> plant that are widely used for the treatment of various medical conditions and recreational use. Common examples include Δ<sup>9</sup>-tetrahydrocannabinol (THC), cannabidiol (CBD), spice, and 2-arachidonoylglycerol (2-AG). With more than 100 cannabinoids identified, their influence on the nervous system, role in pain management, and effects due to illicit use have been extensively studied. However, their effects on peripheral organs, such as the kidneys, require further examination. With dramatic rises in use, production, and legalization, it is essential to understand the impact and mechanistic properties of these drugs as they pertain to renal and cardiovascular physiology. The goal of this review is to summarize prior literature on the expression of cannabinoid receptors and how cannabinoids influence renal function. This review first discusses the interaction of the endocannabinoid system (ECS) and renal physiology and pathophysiology. Following, we briefly discuss the role of the ECS in various kidney diseases and the potential therapeutic applications of drugs targeting the cannabinoid system. Lastly, recent studies have identified several detrimental effects of cannabinoids, not only on the kidney but also in contributing to adverse cardiovascular outcomes. Thus, the negative impact of cannabinoids on renal function and the development of various cardiovascular diseases is also discussed.</p>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"240 12","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142491351","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}
引用次数: 0
Histone deacetylase 6 inhibition promotes microtubule acetylation and facilitates autophagosome–lysosome fusion in dystrophin-deficient mdx mice 抑制组蛋白去乙酰化酶 6 可促进微管乙酰化,并有助于肌营养不良 mdx 小鼠的自噬体-溶酶体融合。
IF 5.6 2区 医学
Acta Physiologica Pub Date : 2024-10-18 DOI: 10.1111/apha.14243
Akanksha Agrawal, Erin L. Clayton, Courtney L. Cavazos, Benjamin A. Clayton, George G. Rodney
{"title":"Histone deacetylase 6 inhibition promotes microtubule acetylation and facilitates autophagosome–lysosome fusion in dystrophin-deficient mdx mice","authors":"Akanksha Agrawal,&nbsp;Erin L. Clayton,&nbsp;Courtney L. Cavazos,&nbsp;Benjamin A. Clayton,&nbsp;George G. Rodney","doi":"10.1111/apha.14243","DOIUrl":"10.1111/apha.14243","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Duchenne muscular dystrophy is a progressive muscle-wasting disease caused by mutations in the dystrophin gene. Despite progress in dystrophin-targeted gene therapies, it is still a fatal disease requiring novel therapeutics that can be used synergistically or alternatively to emerging gene therapy. Defective autophagy and disorganized microtubule networks contribute to dystrophic pathogenesis, yet the mechanisms by which microtubule alterations regulate autophagy remain elusive. The present study was designed to uncover possible mechanisms underpinning the role of microtubules in regulating autophagy in dystrophic mice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p><i>Mdx</i> mice were also supplemented with Tubastatin A, a pharmacological inhibitor of histone deacetylase 6, and pathophysiology was assessed. <i>Mdx</i> mice with a genetic deletion of the Nox-2 scaffolding subunit p47<sup>phox</sup> were used to assess redox dependence on tubulin acetylation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Our data show decreased acetylation of α-tubulin with enhanced histone deacetylase 6 expression. Tubastatin A increases tubulin acetylation and Q-SNARE complex formation but does not alter microtubule organization or density, indicating improved autophagosome–lysosome fusion. Tubastatin A increases the acetylation of peroxiredoxin and protects it from hyper-oxidation, hence modulating intracellular redox status in <i>mdx</i> mice. Tubastatin A reduces muscle damage and enhances force production. Genetic down regulation of Nox2 activity in the <i>mdx</i> mice promotes autophagosome maturation but not autolysosome formation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our data highlight that autophagy is differentially regulated by redox and acetylation in <i>mdx</i> mice. By improving autophagy through promoting tubulin acetylation, Tubastatin A decreases the dystrophic phenotype and improves muscle function, suggesting a great potential for clinical translation and treating dystrophic patients.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142453748","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}
引用次数: 0
Beyond hemoglobin: Critical role of 2,3-bisphosphoglycerate mutase in kidney function and injury 超越血红蛋白:2,3-二磷酸甘油酯突变酶在肾功能和肾损伤中的关键作用。
IF 5.6 2区 医学
Acta Physiologica Pub Date : 2024-10-18 DOI: 10.1111/apha.14242
Vera A. Kulow, Kameliya Roegner, Robert Labes, Mumtaz Kasim, Susanne Mathia, Claudia S. Czopek, Nikolaus Berndt, Philipp N. Becker, Gohar Ter-Avetisyan, Friedrich C. Luft, Philipp Enghard, Christian Hinze, Jan Klocke, Kai-Uwe Eckardt, Kai M. Schmidt-Ott, Pontus B. Persson, Christian Rosenberger, Michael Fähling
{"title":"Beyond hemoglobin: Critical role of 2,3-bisphosphoglycerate mutase in kidney function and injury","authors":"Vera A. Kulow,&nbsp;Kameliya Roegner,&nbsp;Robert Labes,&nbsp;Mumtaz Kasim,&nbsp;Susanne Mathia,&nbsp;Claudia S. Czopek,&nbsp;Nikolaus Berndt,&nbsp;Philipp N. Becker,&nbsp;Gohar Ter-Avetisyan,&nbsp;Friedrich C. Luft,&nbsp;Philipp Enghard,&nbsp;Christian Hinze,&nbsp;Jan Klocke,&nbsp;Kai-Uwe Eckardt,&nbsp;Kai M. Schmidt-Ott,&nbsp;Pontus B. Persson,&nbsp;Christian Rosenberger,&nbsp;Michael Fähling","doi":"10.1111/apha.14242","DOIUrl":"10.1111/apha.14242","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>2,3-bisphosphoglycerate mutase (BPGM) is traditionally recognized for its role in modulating oxygen affinity to hemoglobin in erythrocytes. Recent transcriptomic analyses, however, have indicated a significant upregulation of BPGM in acutely injured murine and human kidneys, suggesting a potential renal function for this enzyme. Here we aim to explore the physiological role of BPGM in the kidney.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A tubular-specific, doxycycline-inducible <i>Bpgm</i>-knockout mouse model was generated. Histological, immunofluorescence, and proteomic analyses were conducted to examine the localization of BPGM expression and the impact of its knockout on kidney structure and function. In vitro studies were performed to investigate the metabolic consequences of <i>Bpgm</i> knockdown under osmotic stress.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>BPGM expression was localized to the distal nephron and was absent in proximal tubules. Inducible knockout of <i>Bpgm</i> resulted in rapid kidney injury within 4 days, characterized by proximal tubular damage and tubulointerstitial fibrosis. Proteomic analyses revealed involvement of BPGM in key metabolic pathways, including glycolysis, oxidative stress response, and inflammation. In vitro, <i>Bpgm</i> knockdown led to enhanced glycolysis, decreased reactive oxygen species elimination capacity under osmotic stress, and increased apoptosis. Furthermore, interactions between nephron segments and immune cells in the kidney suggested a mechanism for propagating stress signals from distal to proximal tubules.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>BPGM fulfills critical functions beyond the erythrocyte in maintaining glucose metabolism in the distal nephron. Its absence leads to metabolic imbalances, increased oxidative stress, inflammation, and ultimately kidney injury.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11674375/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142453747","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}
引用次数: 0
SUMO: A new perspective to decipher fibrosis SUMO:解读纤维化的新视角
IF 5.6 2区 医学
Acta Physiologica Pub Date : 2024-10-15 DOI: 10.1111/apha.14240
Ling Li, Ping-Ping Gao, Ting-Ting Chen, Nan Li, Hui-Juan Zhang, Meng-Qi Li, Ya-Ning Chen, Wei Wei, Hua Wang, Wu-Yi Sun
{"title":"SUMO: A new perspective to decipher fibrosis","authors":"Ling Li,&nbsp;Ping-Ping Gao,&nbsp;Ting-Ting Chen,&nbsp;Nan Li,&nbsp;Hui-Juan Zhang,&nbsp;Meng-Qi Li,&nbsp;Ya-Ning Chen,&nbsp;Wei Wei,&nbsp;Hua Wang,&nbsp;Wu-Yi Sun","doi":"10.1111/apha.14240","DOIUrl":"10.1111/apha.14240","url":null,"abstract":"<p>Fibrosis is characterized by excessive extracellular matrix (ECM) deposition resulting from dysregulated wound healing and connective tissue repair mechanisms. Excessive accumulation of ECM leads to fibrous tissue formation, impairing organ function and driving the progression of various fibrotic diseases. Recently, the role of small ubiquitin-like modifiers (SUMO) in fibrotic diseases has attracted significant attention. SUMO-mediated SUMOylation, a highly conserved posttranslational modification, participates in a variety of biological processes, including nuclear-cytosolic transport, cell cycle progression, DNA damage repair, and cellular metabolism. Conversely, SUMO-specific proteases cleave the isopeptide bond of SUMO conjugates, thereby regulating the deSUMOylation process. Mounting evidence indicates that SUMOylation and deSUMOylation regulate the functions of several proteins, such as Smad3, NF-κB, and promyelocytic leukemia protein, which are implicated in fibrotic diseases like liver fibrosis, myocardial fibrosis, and pulmonary fibrosis. This review summarizes the role of SUMO in fibrosis-related pathways and explores its pathological relevance in various fibrotic diseases. All evidence suggest that the SUMO pathway is important targets for the development of treatments for fibrotic diseases.</p>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"240 12","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142453749","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}
引用次数: 0
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