Acta Physiologica最新文献

{"title":"How calcineurin inhibitors affect cognition","authors":"Kitti Thiankhaw,&nbsp;Nipon Chattipakorn,&nbsp;Siripron C. Chattipakorn","doi":"10.1111/apha.14161","DOIUrl":"10.1111/apha.14161","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>With a focus on the discrepancy between preclinical and clinical findings, this review will gather comprehensive information about the effects of calcineurin inhibitors (CNI) on cognitive function and related brain pathology from <i>in vitro</i>, <i>in vivo</i>, and clinical studies. We also summarize the potential mechanisms that underlie the pathways related to CNI-induced cognitive impairment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We systematically searched articles in PubMed using keywords ‘calcineurin inhibitor*’ and ‘cognition’ to identify related articles, which the final list pertaining to underlying mechanisms of CNI on cognition.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Several studies have reported an association between calcineurin and the neuropathology of Alzheimer’s disease (AD). AD is the most common neurocognitive disorder associated with amyloid plaques and neurofibrillary tangles in the brain, leading to cognitive impairment. CNI, including tacrolimus and cyclosporin A, are commonly prescribed for patients with transplantation of solid organs such as kidney, liver, or heart, those drugs are currently being used as long-term immunosuppressive therapy. Although preclinical models emphasize the favorable effects of CNI on the restoration of brain pathology due to the impacts of calcineurin on the alleviation of amyloid-beta deposition and tau hyperphosphorylation, or rescuing synaptic and mitochondrial functions, treatment-related neurotoxicity, resulting in cognitive dysfunctions has been observed in clinical settings of patients who received CNI.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Inconsistent results of CNI on cognition from clinical studies have been observed due to impairment of the blood-brain barrier, neuroinflammation mediated by reactive oxygen species, and alteration in mitochondrial fission, and extended research is required to confirm its promising use in cognitive impairment.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"240 7","pages":""},"PeriodicalIF":6.3,"publicationDate":"2024-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140920144","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":"Altered skeletal muscle function and beneficial effects of exercise training in a rat model of induced pulmonary emphysema","authors":"Emilie Passerieux,&nbsp;Elodie Desplanche,&nbsp;Laurie Alburquerque,&nbsp;Quentin Wynands,&nbsp;Axel Bellanger,&nbsp;Anne Virsolvy,&nbsp;Farés Gouzi,&nbsp;Olivier Cazorla,&nbsp;Arnaud Bourdin,&nbsp;Maurice Hayot,&nbsp;Pascal Pomiès","doi":"10.1111/apha.14165","DOIUrl":"10.1111/apha.14165","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Chronic obstructive pulmonary disease (COPD) is characterized by progressive airflow obstruction and development of emphysema. Among the comorbidities associated with COPD, skeletal muscle dysfunction is known to affect exercise capacity and the survival rate of patients. Pulmonary rehabilitation (PR), via exercise training, is essential for COPD patients. However, the response to PR is most often moderate. An animal model that recapitulates critical features of chronic human disease and provides access to muscle function should therefore be useful to improve PR benefits.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We used a rat model of induced emphysema based on pulmonary instillations of elastase (ELA) and lipopolysaccharides (LPS). We assessed the long-term effects of ELA/LPS and the potential effectiveness of endurance training on the skeletal muscle function. In vivo strength of the animals, and ex vivo contractility, endurance, type 1 fiber proportion, fiber cross-sectional area, and capillarization of both soleus and extensor digitorum longus (EDL) were assessed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>An impaired overall muscle strength with decreased force, reduced capillarization, and atrophy of type 1 fiber of EDL was observed in ELA/LPS rats. Soleus was not affected. Endurance training was able to reduce fatigability, and increase type 1 fiber proportion and capillarization of soleus, and improve force, endurance, and capillarization of EDL in control and ELA/LPS rats.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our rat model of induced emphysema, which shares some features with the phenotype present in patients with COPD, could represent a suitable model to study skeletal muscle dysfunction and the effects of exercise training on muscle function in patients.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"240 7","pages":""},"PeriodicalIF":6.3,"publicationDate":"2024-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.14165","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140920143","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":"Striatin knock out induces a gain of function of INa and impaired Ca2+ handling in mESC-derived cardiomyocytes","authors":"P. Benzoni,&nbsp;M. Arici,&nbsp;F. Giannetti,&nbsp;A. Cospito,&nbsp;R. Prevostini,&nbsp;C. Volani,&nbsp;L. Fassina,&nbsp;M. D. Rosato-Siri,&nbsp;A. Metallo,&nbsp;L. Gennaccaro,&nbsp;S. Suffredini,&nbsp;L. Foco,&nbsp;S. Mazzetti,&nbsp;A. Calogero,&nbsp;G. Cappelletti,&nbsp;A. Leibbrandt,&nbsp;U. Elling,&nbsp;F. Broso,&nbsp;J. M. Penninger,&nbsp;P. P. Pramstaller,&nbsp;C. Piubelli,&nbsp;A. Bucchi,&nbsp;M. Baruscotti,&nbsp;A. Rossini,&nbsp;M. Rocchetti,&nbsp;A. Barbuti","doi":"10.1111/apha.14160","DOIUrl":"10.1111/apha.14160","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Striatin (Strn) is a scaffold protein expressed in cardiomyocytes (CMs) and alteration of its expression are described in various cardiac diseases. However, the alteration underlying its pathogenicity have been poorly investigated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We studied the role(s) of cardiac Strn gene (<i>STRN</i>) by comparing the functional properties of CMs, generated from Strn-KO and isogenic WT mouse embryonic stem cell lines.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The spontaneous beating rate of Strn-KO CMs was faster than WT cells, and this correlated with a larger fast I_Na conductance and no changes in I_f. Paced (2–8 Hz) Strn-KO CMs showed prolonged action potential (AP) duration in comparison with WT CMs and this was not associated with changes in I_CaL and I_Kr. Motion video tracking analysis highlighted an altered contraction in Strn-KO CMs; this was associated with a global increase in intracellular Ca²⁺, caused by an enhanced late Na⁺ current density (I_NaL) and a reduced Na⁺/Ca²⁺ exchanger (NCX) activity and expression. Immunofluorescence analysis confirmed the higher Na⁺ channel expression and a more dynamic microtubule network in Strn-KO CMs than in WT. Indeed, incubation of Strn-KO CMs with the microtubule stabilizer taxol, induced a rescue (downregulation) of I_Na conductance toward WT levels.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Loss of <i>STRN</i> alters CMs electrical and contractile profiles and affects cell functionality by a disarrangement of Strn-related multi-protein complexes. This leads to impaired microtubules dynamics and Na⁺ channels trafficking to the plasma membrane, causing a global Na⁺ and Ca²⁺ enhancement.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"240 8","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.14160","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140920145","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 function in skeletal muscle contributes to reproductive endothermy in tegu lizards (Salvator merianae)","authors":"Livia Saccani Hervas,&nbsp;Lara do Amaral-Silva,&nbsp;Marina Rincon Sartori,&nbsp;Ane Guadalupe-Silva,&nbsp;Luciane H. Gargaglioni,&nbsp;Johannes Lerchner,&nbsp;Marcos Túlio Oliveira,&nbsp;Kênia Cardoso Bícego","doi":"10.1111/apha.14162","DOIUrl":"10.1111/apha.14162","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>In cyclic climate variations, including seasonal changes, many animals regulate their energy demands to overcome critical transitory moments, restricting their high-demand activities to phases of resource abundance, enabling rapid growth and reproduction. Tegu lizards (<i>Salvator merianae</i>) are ectotherms with a robust annual cycle, being active during summer, hibernating during winter, and presenting a remarkable endothermy during reproduction in spring. Here, we evaluated whether changes in mitochondrial respiratory physiology in skeletal muscle could serve as a mechanism for the increased thermogenesis observed during the tegu's reproductive endothermy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We performed high-resolution respirometry and calorimetry in permeabilized red and white muscle fibers, sampled during summer (activity) and spring (high activity and reproduction), in association with citrate synthase measurements.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>During spring, the muscle fibers exhibited increased oxidative phosphorylation. They also enhanced uncoupled respiration and heat production via adenine nucleotide translocase (ANT), but not via uncoupling proteins (UCP). Citrate synthase activity was higher during the spring, suggesting greater mitochondrial density compared to the summer. These findings were consistent across both sexes and muscle types (red and white).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The current results highlight potential cellular thermogenic mechanisms in an ectothermic reptile that contribute to transient endothermy. Our study indicates that the unique feature of transitioning to endothermy through nonshivering thermogenesis during the reproductive phase may be facilitated by higher mitochondrial density, function, and uncoupling within the skeletal muscle. This knowledge contributes significant elements to the broader picture of models for the evolution of endothermy, particularly in relation to the enhancement of aerobic capacity.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"240 7","pages":""},"PeriodicalIF":6.3,"publicationDate":"2024-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140915472","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":"Time-dependent reduction in oxidative capacity among cultured myotubes from spinal cord injured individuals","authors":"Stanislava Stevanovic,&nbsp;Andrea Dalmao-Fernandez,&nbsp;Derya Mohamed,&nbsp;Tuula A. Nyman,&nbsp;Emil Kostovski,&nbsp;Per Ole Iversen,&nbsp;Mladen Savikj,&nbsp;Natasa Nikolic,&nbsp;Arild C. Rustan,&nbsp;G. Hege Thoresen,&nbsp;Eili T. Kase","doi":"10.1111/apha.14156","DOIUrl":"10.1111/apha.14156","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Skeletal muscle adapts in reaction to contractile activity to efficiently utilize energy substrates, primarily glucose and free fatty acids (FA). Inactivity leads to atrophy and a change in energy utilization in individuals with spinal cord injury (SCI). The present study aimed to characterize possible inactivity-related differences in the energy metabolism between skeletal muscle cells cultured from satellite cells isolated 1- and 12-months post-SCI.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>To characterize inactivity-related disturbances in spinal cord injury, we studied skeletal muscle cells isolated from SCI subjects. Cell cultures were established from biopsy samples from <i>musculus vastus lateralis</i> from subjects with SCI 1 and 12 months after the injury. The myoblasts were proliferated and differentiated into myotubes before fatty acid and glucose metabolism were assessed and gene and protein expressions were measured.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The results showed that glucose uptake was increased, while oleic acid oxidation was reduced at 12 months compared to 1 month. mRNA expressions of <i>PPARGC1α</i>, the master regulator of mitochondrial biogenesis, and <i>MYH2</i>, a determinant of muscle fiber type, were significantly reduced at 12 months. Proteomic analysis showed reduced expression of several mitochondrial proteins.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>In conclusion, skeletal muscle cells isolated from immobilized subjects 12 months compared to 1 month after SCI showed reduced fatty acid metabolism and reduced expression of mitochondrial proteins, indicating an increased loss of oxidative capacity with time after injury.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"240 7","pages":""},"PeriodicalIF":6.3,"publicationDate":"2024-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.14156","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140848906","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":"Regulation of placental amino acid transport in health and disease","authors":"Hiroshi Shimada,&nbsp;Theresa L. Powell,&nbsp;Thomas Jansson","doi":"10.1111/apha.14157","DOIUrl":"10.1111/apha.14157","url":null,"abstract":"<p>Abnormal fetal growth, i.e., intrauterine growth restriction (IUGR) or fetal growth restriction (FGR) and fetal overgrowth, is associated with increased perinatal morbidity and mortality and is strongly linked to the development of metabolic and cardiovascular disease in childhood and later in life. Emerging evidence suggests that changes in placental amino acid transport may contribute to abnormal fetal growth. This review is focused on amino acid transport in the human placenta, however, relevant animal models will be discussed to add mechanistic insights. At least 25 distinct amino acid transporters with different characteristics and substrate preferences have been identified in the human placenta. Of these, System A, transporting neutral nonessential amino acids, and System L, mediating the transport of essential amino acids, have been studied in some detail. Importantly, decreased placental Systems A and L transporter activity is strongly associated with IUGR and increased placental activity of these two amino acid transporters has been linked to fetal overgrowth in human pregnancy. An array of factors in the maternal circulation, including insulin, IGF-1, and adiponectin, and placental signaling pathways such as mTOR, have been identified as key regulators of placental Systems A and L. Studies using trophoblast-specific gene targeting in mice have provided compelling evidence that changes in placental Systems A and L are mechanistically linked to altered fetal growth. It is possible that targeting specific placental amino acid transporters or their upstream regulators represents a novel intervention to alleviate the short- and long-term consequences of abnormal fetal growth in the future.</p>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"240 7","pages":""},"PeriodicalIF":6.3,"publicationDate":"2024-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140848324","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":"Effects of thiazides and new findings on kidney stones and dysglycemic side effects","authors":"Matteo Bargagli,&nbsp;Manuel A. Anderegg,&nbsp;Daniel G. Fuster","doi":"10.1111/apha.14155","DOIUrl":"10.1111/apha.14155","url":null,"abstract":"<p>Thiazide and thiazide-like diuretics (thiazides) belong to the most frequently prescribed drugs worldwide. By virtue of their natriuretic and vasodilating properties, thiazides effectively lower blood pressure and prevent adverse cardiovascular outcomes. In addition, through their unique characteristic of reducing urine calcium, thiazides are also widely employed for the prevention of kidney stone recurrence and reduction of bone fracture risk. Since their introduction into clinical medicine in the early 1960s, thiazides have been recognized for their association with metabolic side effects, particularly impaired glucose tolerance, and new-onset diabetes mellitus. Numerous hypotheses have been advanced to explain thiazide-induced glucose intolerance, yet underlying mechanisms remain poorly defined. Regrettably, the lack of understanding and unpredictability of these side effects has prompted numerous physicians to refrain from prescribing these effective, inexpensive, and widely accessible drugs. In this review, we outline the pharmacology and mechanism of action of thiazides, highlight recent advances in the understanding of thiazide-induced glucose intolerance, and provide an up-to-date discussion on the role of thiazides in kidney stone prevention.</p>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"240 7","pages":""},"PeriodicalIF":6.3,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.14155","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140834350","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":"Current insights into the Pathophysiology of kidney diseases","authors":"Anika Westphal","doi":"10.1111/apha.14158","DOIUrl":"10.1111/apha.14158","url":null,"abstract":"&lt;p&gt;Chronic kidney disease (CKD) affects 700–800 million humans per year.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; Damage to the kidney is often recognized late, although early diagnosis is essential for successful treatment. While acute kidney injury can often be effectively managed, CKD poses a challenge due to irreversible structural damage, compromising intrinsic kidney functions such as regulation of fluid, electrolyte, and acid–base balance, and the release of hormones into the blood, for example, renin and erythropoietin (Epo). The decrease in the glomerular filtration rate (GFR) and the increase in albumin in the urine are the most important markers in the diagnosis of kidney diseases. This article presents novel findings on kidney diseases, potential approaches for future therapies and new impacts in preventing and treating different stages of renal diseases, recently published in &lt;i&gt;Acta Physiologica&lt;/i&gt;.&lt;/p&gt;&lt;p&gt;Early diagnosis of acute kidney injury (AKI) is of high importance for an adequate treatment. However, revealing early events in AKI is challenging, due to the absence of clear symptoms. Several urine- or blood-based markers for renal injury, fibrosis etc. have been suggested, with varying outcomes. In most forms of AKI, renal tissue hypoxia is an early marker. Hypoxia of the kidney tissue is also involved in the development of chronic and diabetic kidney disease. Kidney hypoxia often comes along with changes in kidney size. Cantow et al. analyzed in a magnetic resonance imaging (MRI)-based approach the connection between kidney size and renal tissue hypoxia. To achieve this, they used different interventions impairing renal tissue oxygenation, for example, occlusions and hypoxemia. MRI markers, kidney size, and their interactions were analyzed. In summary, observation of kidney size enables the interpretation of pathophysiological changes in kidney oxygenation. They conclude that monitoring of kidney size should always accompany MRI oximetry to gain essential information about renal disease levels, especially in acute changes in renal tissue oxygenation in AKI and its progression to CKD.&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;Betrie et al. and Xu et al. focus on exploring preventive measures against AKI in ovine and rat models. Half of the patients with sepsis develop AKI and thereby have a higher morbidity and mortality. In ovine sepsis, hypoxia and renal medullary hypoperfusion is often followed by AKI, probably due to inflammation and oxidative stress. So far, there is a lack of specific renal-protective therapies available that focuses on the reduction of inflammation and the increased bioavailability of reactive oxygen and nitrogen species that appear in the kidneys. Betrie et al. investigated a possible protective effect of tempol on the development of AKI following sepsis. Tempol is a synthetic heterocyclic nitroxide that has a positive effect on reducing oxidative stress, increasing the bioavailability of nitric oxide and inhibiting inflammation","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"240 7","pages":""},"PeriodicalIF":6.3,"publicationDate":"2024-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.14158","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140834351","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":"Mechanosensing by Piezo1 and its implications in the kidney","authors":"Xi Yuan,&nbsp;Xiaoduo Zhao,&nbsp;Weidong Wang,&nbsp;Chunling Li","doi":"10.1111/apha.14152","DOIUrl":"10.1111/apha.14152","url":null,"abstract":"<p>Piezo1 is an essential mechanosensitive transduction ion channel in mammals. Its unique structure makes it capable of converting mechanical cues into electrical and biological signals, modulating biological and (patho)physiological processes in a wide variety of cells. There is increasing evidence demonstrating that the piezo1 channel plays a vital role in renal physiology and disease conditions. This review summarizes the current evidence on the structure and properties of Piezo1, gating modulation, and pharmacological characteristics, with special focus on the distribution and (patho)physiological significance of Piezo1 in the kidney, which may provide insights into potential treatment targets for renal diseases involving this ion channel.</p>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"240 6","pages":""},"PeriodicalIF":6.3,"publicationDate":"2024-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140834403","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":"Landscape of transcriptome-wide m6A modification in diabetic liver reveals rewiring of PI3K-Akt signaling after physical exercise","authors":"Cong Chen,&nbsp;Cai Jiang,&nbsp;Ting Lin,&nbsp;Yue Hu,&nbsp;Huijuan Wu,&nbsp;Qing Xiang,&nbsp;Minguang Yang,&nbsp;Sinuo Wang,&nbsp;Xiao Han,&nbsp;Jing Tao","doi":"10.1111/apha.14154","DOIUrl":"10.1111/apha.14154","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Type 2 diabetes mellitus (T2DM) is one of the most common diseases, and epigenetic modification N6-methyladenosine (m⁶A) is essential for transcriptional modulation involved in its development. However, the precise role and landscape of transcriptome-wide m⁶A alterations in molecular adaptations after physical exercise have yet to be fully elucidated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Four-week-old male C57BL/6J mice received a high-fat diet (HFD) for 12 weeks to establish a diabetic state, and HFD mice were simultaneously subjected to physical exercise (HFD + EX). The hepatic RNA m⁶A methylome was examined, the conjoint MeRIP-seq and RNA-seq was performed, and the exercise-modulated genes were confirmed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Physical exercise significantly ameliorates liver metabolic disorder and triggers a dynamic change in hepatic RNA m⁶A. By analyzing the distribution of m⁶A in transcriptomes, an abundance of m⁶A throughout mRNA transcripts and a pattern of conserved m⁶A after physical exercise was identified. It is noteworthy that conjoint MeRIP-seq and RNA-seq data revealed that both differentially methylated genes and differentially expressed genes were enriched in all stages of the PI3K-Akt signaling pathway, in particular the upstream nodes of this pathway, which are considered a valuable therapeutic target for T2DM. Moreover, in vivo and in vitro analyses showed that exercise-mediated methyltransferase Rbm15 positively regulated the expression of two upstream genes (Itga3 and Fgf21) in an m⁶A-dependent manner.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>These findings highlight the pivotal role of the exercise-induced m⁶A epigenetic network and contribute insights into the intricate epigenetic mechanism underlying insulin signaling.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"240 6","pages":""},"PeriodicalIF":6.3,"publicationDate":"2024-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.14154","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140834355","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}