Acta Physiologica最新文献

{"title":"Natural Mutation in Naked Mole-Rat UCP1 Refutes Importance of the Histidine Pair Motif for Proton Conductance and Thermogenesis","authors":"Michael J. Gaudry,&nbsp;Amanda Bundgaard,&nbsp;Maria Kutschke,&nbsp;Klaudia Ostatek,&nbsp;Margeoux A. S. Dela Rosa,&nbsp;Paul G. Crichton,&nbsp;Jane Reznick,&nbsp;Martin Jastroch","doi":"10.1111/apha.70109","DOIUrl":"10.1111/apha.70109","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Uncoupling protein 1 (UCP1) is the crucial protein for non-shivering thermogenesis in placental mammals, but the molecular mechanism of thermogenic proton transport is still unknown. Its histidine pair motif (H145 and H147) has been claimed as a critical element for proton translocation, leading to the paradigmatic “cofactor model” of the UCP1 thermogenic mechanism. The histidine pair motif is mutated (H145Q) in the naked mole-rat (NMR, <i>Heterocephalus glaber</i>) UCP1, suggesting disrupted thermogenic function in line with NMR's poor thermoregulatory abilities. Here, we investigated the functionality NMR versus mouse UCP1 to scrutinized the importance of the histidine pair motif.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Respiratory analyses for UCP1 function were performed in isolated brown adipose tissue mitochondria from NMR and mouse. The histidine pair motif of NMR UCP1 was manipulated through mutations, ectopically overexpressed in HEK293 cells and subjected to plate-based respirometry for functional comparison.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Isolated BAT mitochondria of NMRs display guanosine diphosphate-sensitive respiration, indicative of thermogenically competent UCP1. Overexpressed wildtype NMR UCP1 demonstrates proton leak activity comparable to mouse UCP1. Neither restoration of the histidine pair motif nor full ablation of the motif through a double mutation affects UCP1-dependent respiration.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The UCP1 variant of the NMR, a warm-adapted fossorial species, excludes the histidine pair motif as crucial for UCP1 thermogenic function. Collectively, we show that functional investigation into natural sequence variation of UCP1 not only casts new light on the thermophysiology of NMRs but also represents a powerful tool to delineate structure-function relationships underlying the enigmatic thermogenic proton transport of UCP1.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 10","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.70109","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145129640","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":"Beyond Being a Biomarker: Lipocalin-2/NGAL as a Facilitator for Protective Drug Action in Hypoxic Kidney Injury","authors":"Boye L. Jensen","doi":"10.1111/apha.70110","DOIUrl":"10.1111/apha.70110","url":null,"abstract":"&lt;p&gt;In the present issue of &lt;i&gt;Acta Physiologica&lt;/i&gt; [&lt;span&gt;1&lt;/span&gt;], an international consortium of investigators reports that the iron-transporter glycoprotein lipocalin-2 (LCN2), originally identified in neutrophils and named &lt;i&gt;neutrophil gelatinase-associated lipocalin&lt;/i&gt;, abbreviated NGAL or 24p3, may protect the kidneys from ischemia–reperfusion injury. The findings suggest that LCN2 protects the kidneys by restoring the sensitivity of soluble guanylate cyclase (sGC) to drug activators in afferent glomerular arterioles through a receptor-mediated mechanism. LCN2 is produced and released by several tissues including adipose tissue, liver, kidneys, and neutrophils. It is categorized as an acute-phase protein that is upregulated during inflammatory states. LCN2 is widely used in clinical and experimental settings as an early biomarker in acute kidney injury and for the staging of chronic kidney disease.&lt;/p&gt;&lt;p&gt;The study by Zhao et al. [&lt;span&gt;1&lt;/span&gt;] is an elegant follow-up study on a series of independent observations dating 10–20 years back, which include a study by authors from 2016 [&lt;span&gt;2&lt;/span&gt;]. A consistent kidney-protective effect of exogenous LCN2 was found in preclinical kidney ischemia-injury models, including a kidney transplantation model. The study in &lt;i&gt;Acta&lt;/i&gt; shows ex vivo with murine, isolated kidney microvessels, that LCN2 mitigates excessive microvascular resistance through restoring vascular smooth sGC sensitivity towards activator drugs. The sensitivity is typically lost by more severe prolonged hypoxia. Soluble GCs can be oxidized to the heme-free form, apo-sGC, and the authors confirm that apo-sGC cannot be activated by the endogenous agonist nitric oxide (NO). The class of sGC activator drugs is unique and different from sGC stimulators since they can overcome this state and activate apo-sGC independently of NO to increase target cell cyclic guanosine monophosphate (cGMP) production even under detrimental oxidative stress. Zhao et al. [&lt;span&gt;1&lt;/span&gt;] show that LCN2 restores sensitivity of the kidney afferent arterioles towards sGC activators dependent on iron. The effect is found in arterioles subjected to hypoxia ex vivo after isolation and in arterioles subjected to hypoxia “in situ” in transplanted kidneys before microdissection and testing. The conclusion is that by delivering ferric iron bound to LCN2 (holo-LCN2) to arterioles, this oxidizes sGC, which restores sensitivity to activator drugs. The study corroborates that LCN2 may be a direct, extracellular, signaling molecule that indirectly protects vascular smooth muscle suffering from prolonged ischemic insults in the kidneys (Figure 1).&lt;/p&gt;&lt;p&gt;What is the mechanism? LCN2 binds hydrophobic microbial siderophores, which are small molecules that bacteria produce to sequester iron from their environment. The acute phase reactant LCN2 is thereby bacteriostatic since iron is a vital nutrient for many microbes. Deletion of LCN2 increases susceptibility to &lt;i&gt;Esch","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 10","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.70110","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145123858","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":"Micro-Embolic Events and Their Clearing in the Brain. A Narrative Review","authors":"Kevin Mol,&nbsp;Inge A. Mulder,&nbsp;Ed van Bavel","doi":"10.1111/apha.70098","DOIUrl":"https://doi.org/10.1111/apha.70098","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The cerebral circulation is continuously challenged by intravascular micrometer-sized particles that become trapped microvascular-emboli. These particles may include micro-thrombi, stiffened erythrocytes, and leukocytes, while also fat particles, air, and microplastics may cause microvascular embolism.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Review Scope</h3>\u0000 \u0000 <p>In this narrative review, we discuss these embolization processes and their acute and chronic consequences. These relate to the local flow interruption as well as the direct interaction with the endothelium. In addition, we address the clearing processes, including local thrombolysis and extravasation, or angiophagy, of the emboli.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>A continuous balance exists between embolic events and their resolution under normal conditions. Increased micro-embolic rates, as occur in e.g., atrial fibrillation, or decreased clearing, possibly related to endothelial cell dysfunction, disturb this balance. This could lead to continuing loss of capillaries, micro-infarcts, and cognitive decline.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 10","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.70098","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145021990","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":"Poster Session B","authors":"","doi":"10.1111/apha.70105","DOIUrl":"https://doi.org/10.1111/apha.70105","url":null,"abstract":"","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 S735","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145012239","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":"Symposia","authors":"","doi":"10.1111/apha.70101","DOIUrl":"https://doi.org/10.1111/apha.70101","url":null,"abstract":"","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 S735","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145012241","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":"Oral Sessions","authors":"","doi":"10.1111/apha.70103","DOIUrl":"https://doi.org/10.1111/apha.70103","url":null,"abstract":"","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 S735","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145012242","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":"Special Lectures","authors":"","doi":"10.1111/apha.70099","DOIUrl":"https://doi.org/10.1111/apha.70099","url":null,"abstract":"","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 S735","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145012489","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":"Poster Session C","authors":"","doi":"10.1111/apha.70104","DOIUrl":"https://doi.org/10.1111/apha.70104","url":null,"abstract":"","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 S735","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145012240","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":"Plenary Lectures","authors":"","doi":"10.1111/apha.14285","DOIUrl":"https://doi.org/10.1111/apha.14285","url":null,"abstract":"","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 S735","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145012286","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":"Poster Session A","authors":"","doi":"10.1111/apha.70102","DOIUrl":"https://doi.org/10.1111/apha.70102","url":null,"abstract":"","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 S735","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145012287","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}