Function (Oxford, England)最新文献

Exploring Circadian Changes in Muscle Physiology: Methodological Considerations. 探索肌肉生理学的昼夜节律变化：方法论方面的考虑。

IF 5.1

Function (Oxford, England) Pub Date : 2024-09-03 DOI: 10.1093/function/zqae038

Mark R Viggars, Karyn A Esser

引用次数: 0

Malaria and Hypertension: What Is the Direction of Association? 疟疾与高血压：关联的方向是什么？

IF 5.1

Function (Oxford, England) Pub Date : 2024-08-30 DOI: 10.1093/function/zqae037

Aparna Tiwari, Auley De, Abhinav Sinha

引用次数: 0

Impaired neurocirculatory control in chronic kidney disease: New evidence for blunted sympathetic baroreflex and reduced sympathetic transduction. 慢性肾脏病的神经循环控制受损：交感神经巴氏反射减弱和交感神经传导功能降低的新证据。

IF 5.1

Function (Oxford, England) Pub Date : 2024-08-23 DOI: 10.1093/function/zqae036

Jeann L Sabino-Carvalho, Elsa Mekonnen, Matias Zanuzzi, Sabrina Li, Xiangqin Cui, Jeanie Park

{"title":"Impaired neurocirculatory control in chronic kidney disease: New evidence for blunted sympathetic baroreflex and reduced sympathetic transduction.","authors":"Jeann L Sabino-Carvalho, Elsa Mekonnen, Matias Zanuzzi, Sabrina Li, Xiangqin Cui, Jeanie Park","doi":"10.1093/function/zqae036","DOIUrl":"https://doi.org/10.1093/function/zqae036","url":null,"abstract":"Background: Chronic kidney disease (CKD) is characterized by over-activation of the sympathetic nervous system (SNS) that increases cardiovascular risk. Whether sympathetic baroreflex sensitivity (sBRS) is impaired or intact in CKD remains under-studied and controversial. Furthermore, the downstream effect of SNS activation on blood pressure transduction has not been previously examined in CKD. We tested the hypothesis that sBRS is attenuated, while sympathetic transduction is augmented in CKD.Methods: In 18 sedentary patients with CKD stages III-IV (eGFR: 40±14 ml/min) and 13 age-matched controls (eGFR: 95±10 ml/min), beat-to-beat blood pressure (BP; finger photoplethysmography), heart rate (electrocardiography) and muscle sympathetic nerve activity (MSNA; microneurography) were recorded at rest for 10-min. Weighted linear regression analysis between MSNA burst incidence and diastolic BP was used to determine the spontaneous sBRS. Sympathetic-BP transduction was quantified using signal averaging, whereby the BP response to each MSNA burst was tracked over 15 cardiac cycles and averaged to derive the peak change in BP.Results: Compared with controls, CKD patients had an attenuated sBRS [CKD: -1.34±0.59 versus CON: -2.91±1.09 bursts (100 heartbeats)-1 mmHg-1; P=0.001]. |sBRS| was significantly associated with eGFR (r=0.69, P<0.001). CKD patients had attenuated sympathetic-BP transduction compared to controls (0.75±0.7 vs. 1.60±0.8 mmHg; P=0.010). Resting MSNA was negatively associated with sympathetic transduction (r=-0.57, P=0.002).Conclusion: CKD patients exhibit impaired sBRS that may contribute to SNS overactivation and cardiovascular risk in this patient population. In addition, CKD patients had an attenuated sympathetic transduction that may counteract the vascular effects of SNS overactivation.","PeriodicalId":73119,"journal":{"name":"Function (Oxford, England)","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142047565","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Intrinsic Skeletal Muscle Function and Contraction-stimulated Glucose Uptake Do Not Vary by Time-of-day in Mice. 小鼠骨骼肌内在功能和收缩刺激的葡萄糖摄取量不随时间而变化

IF 5.1

Function (Oxford, England) Pub Date : 2024-08-12 DOI: 10.1093/function/zqae035

Liam S Fitzgerald, Shannon N Bremner, Samuel R Ward, Yoshitake Cho, Simon Schenk

{"title":"Intrinsic Skeletal Muscle Function and Contraction-stimulated Glucose Uptake Do Not Vary by Time-of-day in Mice.","authors":"Liam S Fitzgerald, Shannon N Bremner, Samuel R Ward, Yoshitake Cho, Simon Schenk","doi":"10.1093/function/zqae035","DOIUrl":"10.1093/function/zqae035","url":null,"abstract":"A growing body of data suggests that skeletal muscle contractile function and glucose metabolism vary by time-of-day, with chronobiological effects on intrinsic skeletal muscle properties being proposed as the underlying mediator. However, no studies have directly investigated intrinsic contractile function or glucose metabolism in skeletal muscle over a 24 h circadian cycle. To address this, we assessed intrinsic contractile function and endurance, as well as contraction-stimulated glucose uptake, in isolated extensor digitorum longus and soleus from mice at four times-of-day (zeitgeber times 1, 7, 13, 19). Significantly, though both muscles demonstrated circadian-related changes in gene expression, there were no differences between the four time points in intrinsic contractile function, endurance, and contraction-stimulated glucose uptake, regardless of sex. Overall, these results suggest that time-of-day variation in exercise performance and the glycemia-reducing benefits of exercise are not due to chronobiological effects on intrinsic muscle function or contraction-stimulated glucose uptake.","PeriodicalId":73119,"journal":{"name":"Function (Oxford, England)","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141972405","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Managing SABV in Physiological Research: Best Practices. 管理生理学研究中的 SABV：最佳实践。

IF 5.1

Function (Oxford, England) Pub Date : 2024-08-05 DOI: 10.1093/function/zqae034

Candee Barris, Emily Burns-Ray, Jennifer C Sullivan

引用次数: 0

Acute Metabolic Stress Induces Lymphatic Dysfunction through KATP Channel Activation. 急性代谢压力通过激活 KATP 通道诱发淋巴功能障碍

IF 5.1

Function (Oxford, England) Pub Date : 2024-07-29 DOI: 10.1093/function/zqae033

Hae Jin Kim, Charles E Norton, Scott D Zawieja, Jorge A Castorena-Gonzalez, Michael J Davis

{"title":"Acute Metabolic Stress Induces Lymphatic Dysfunction through KATP Channel Activation.","authors":"Hae Jin Kim, Charles E Norton, Scott D Zawieja, Jorge A Castorena-Gonzalez, Michael J Davis","doi":"10.1093/function/zqae033","DOIUrl":"https://doi.org/10.1093/function/zqae033","url":null,"abstract":"Lymphatic dysfunction is an underlying component of multiple metabolic diseases, including diabetes, obesity, and metabolic syndrome. We investigated the roles of KATP channels in lymphatic contractile dysfunction in response to acute metabolic stress induced by inhibition of the mitochondrial electron transport chain. Ex vivo popliteal lymphatic vessels from mice were exposed to the electron transport chain inhibitors antimycin A and rotenone, or the oxidative phosphorylation inhibitor/protonophore, CCCP. Each inhibitor led to a significant reduction in the frequency of spontaneous lymphatic contractions and calculated pump flow, without a significant change in contraction amplitude. Contraction frequency was restored by the KATP channel inhibitor, glibenclamide. Lymphatic vessels from mice with global Kir6.1 deficiency or expressing a smooth muscle-specific dominant negative Kir6.1 channel were resistant to inhibition. Antimycin A inhibited the spontaneous action potentials generated in lymphatic muscle and this effect was reversed by glibenclamide, confirming the role of KATP channels. Antimycin A, but not rotenone or CCCP, increased dihydrorhodamine fluorescence in lymphatic muscle, indicating ROS production. Pretreatment with tiron or catalase prevented the effect of antimycin A on wild-type lymphatic vessels, consistent with its action being mediated by ROS. Our results support the conclusion that KATP channels in lymphatic muscle can be directly activated by reduced mitochondrial ATP production or ROS generation, consequent to acute metabolic stress, leading to contractile dysfunction through inhibition of the ionic pacemaker controlling spontaneous lymphatic contractions. We propose that a similar activation of KATP channels contributes to lymphatic dysfunction in metabolic disease.","PeriodicalId":73119,"journal":{"name":"Function (Oxford, England)","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141794186","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The P2X7 Receptor is a Master Regulator of Microparticle and Mitochondria Exchange in Mouse Microglia. P2×7 受体是小鼠小胶质细胞微粒和线粒体交换的主调节器。

IF 5.1

Function (Oxford, England) Pub Date : 2024-07-11 DOI: 10.1093/function/zqae019

Simonetta Falzoni, Valentina Vultaggio-Poma, Paola Chiozzi, Mario Tarantini, Elena Adinolfi, Paola Boldrini, Anna Lisa Giuliani, Giampaolo Morciano, Yong Tang, Dariusz C Gorecki, Francesco Di Virgilio

{"title":"The P2X7 Receptor is a Master Regulator of Microparticle and Mitochondria Exchange in Mouse Microglia.","authors":"Simonetta Falzoni, Valentina Vultaggio-Poma, Paola Chiozzi, Mario Tarantini, Elena Adinolfi, Paola Boldrini, Anna Lisa Giuliani, Giampaolo Morciano, Yong Tang, Dariusz C Gorecki, Francesco Di Virgilio","doi":"10.1093/function/zqae019","DOIUrl":"10.1093/function/zqae019","url":null,"abstract":"Microparticles (MPs) are secreted by all cells, where they play a key role in intercellular communication, differentiation, inflammation, and cell energy transfer. P2X7 receptor (P2X7R) activation by extracellular ATP (eATP) causes a large MP release and affects their contents in a cell-specific fashion. We investigated MP release and functional impact in microglial cells from P2X7R-WT or P2X7R-KO mice, as well as mouse microglial cell lines characterized for high (N13-P2X7RHigh) or low (N13-P2X7RLow) P2X7R expression. P2X7R stimulation promoted release of a mixed MP population enriched with naked mitochondria. Released mitochondria were taken up and incorporated into the mitochondrial network of the recipient cells in a P2X7R-dependent fashion. NLRP3 and the P2X7R itself were also delivered to the recipient cells. Microparticle transfer increased the energy level of the recipient cells and conferred a pro-inflammatory phenotype. These data show that the P2X7R is a master regulator of intercellular organelle and MP trafficking in immune cells.","PeriodicalId":73119,"journal":{"name":"Function (Oxford, England)","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11237899/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141565335","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Megalin Knockout Reduces SGLT2 Expression and Sensitizes to Western Diet-induced Kidney Injury. Megalin基因敲除可减少SGLT2的表达，并对西方饮食诱导的肾损伤敏感。

IF 5.1

Function (Oxford, England) Pub Date : 2024-07-11 DOI: 10.1093/function/zqae026

Elynna B Youm, Katherine E Shipman, Wafaa N Albalawy, Amber M Vandevender, Ian J Sipula, Youssef Rbaibi, Allison E Marciszyn, Jared A Lashway, Emma E Brown, Corry B Bondi, Cary R Boyd-Shiwarski, Roderick J Tan, Michael J Jurczak, Ora A Weisz

{"title":"Megalin Knockout Reduces SGLT2 Expression and Sensitizes to Western Diet-induced Kidney Injury.","authors":"Elynna B Youm, Katherine E Shipman, Wafaa N Albalawy, Amber M Vandevender, Ian J Sipula, Youssef Rbaibi, Allison E Marciszyn, Jared A Lashway, Emma E Brown, Corry B Bondi, Cary R Boyd-Shiwarski, Roderick J Tan, Michael J Jurczak, Ora A Weisz","doi":"10.1093/function/zqae026","DOIUrl":"10.1093/function/zqae026","url":null,"abstract":"Megalin (Lrp2) is a multiligand receptor that drives endocytic flux in the kidney proximal tubule (PT) and is necessary for the recovery of albumin and other filtered proteins that escape the glomerular filtration barrier. Studies in our lab have shown that knockout (KO) of Lrp2 in opossum PT cells leads to a dramatic reduction in sodium-glucose co-transporter 2 (SGLT2) transcript and protein levels, as well as differential expression of genes involved in mitochondrial and metabolic function. SGLT2 transcript levels are reduced more modestly in Lrp2 KO mice. Here, we investigated the effects of Lrp2 KO on kidney function and health in mice fed regular chow (RC) or a Western-style diet (WD) high in fat and refined sugar. Despite a modest reduction in SGLT2 expression, Lrp2 KO mice on either diet showed increased glucose tolerance compared to control mice. Moreover, Lrp2 KO mice were protected against WD-induced fat gain. Surprisingly, renal function in male Lrp2 KO mice on WD was compromised, and the mice exhibited significant kidney injury compared with control mice on WD. Female Lrp2 KO mice were less susceptible to WD-induced kidney injury than male Lrp2 KO. Together, our findings reveal both positive and negative contributions of megalin expression to metabolic health, and highlight a megalin-mediated sex-dependent response to injury following WD.","PeriodicalId":73119,"journal":{"name":"Function (Oxford, England)","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11237895/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141565332","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Sex-Specific Effects of Cholesteryl Ester Transfer Protein (CETP) on the Perivascular Adipose Tissue. 胆固醇酯转移蛋白 (CETP) 对血管周围脂肪组织的性别特异性影响

IF 5.1

Function (Oxford, England) Pub Date : 2024-07-11 DOI: 10.1093/function/zqae024

C M Lazaro, I N Freitas, V S Nunes, D M Guizoni, J A Victorio, H C F Oliveira, A P Davel

{"title":"Sex-Specific Effects of Cholesteryl Ester Transfer Protein (CETP) on the Perivascular Adipose Tissue.","authors":"C M Lazaro, I N Freitas, V S Nunes, D M Guizoni, J A Victorio, H C F Oliveira, A P Davel","doi":"10.1093/function/zqae024","DOIUrl":"10.1093/function/zqae024","url":null,"abstract":"Cholesteryl ester transfer protein (CETP) increases the atherosclerosis risk by lowering HDL-cholesterol levels. It also exhibits tissue-specific effects independent of HDL. However, sexual dimorphism of CETP effects remains largely unexplored. Here, we hypothesized that CETP impacts the perivascular adipose tissue (PVAT) phenotype and function in a sex-specific manner. PVAT function, gene and protein expression, and morphology were examined in male and female transgenic mice expressing human or simian CETP and their non-transgenic counterparts (NTg). PVAT exerted its anticontractile effect in aortas from NTg males, NTg females, and CETP females, but not in CETP males. CETP male PVAT had reduced NO levels, decreased eNOS and phospho-eNOS levels, oxidative stress, increased NOX1 and 2, and decreased SOD2 and 3 expressions. In contrast, CETP-expressing female PVAT displayed increased NO and phospho-eNOS levels with unchanged NOX expression. NOX inhibition and the antioxidant tempol restored PVAT anticontractile function in CETP males. Ex vivo estrogen treatment also restored PVAT function in CETP males. Moreover, CETP males, but not female PVAT, show increased inflammatory markers. PVAT lipid content increased in CETP males but decreased in CETP females, while PVAT cholesterol content increased in CETP females. CETP male PVAT exhibited elevated leptin and reduced Prdm16 (brown adipocyte marker) expression. These findings highlight CETP sex-specific impact on PVAT. In males, CETP impaired PVAT anticontractile function, accompanied by oxidative stress, inflammation, and whitening. Conversely, in females, CETP expression increased NO levels, induced an anti-inflammatory phenotype, and preserved the anticontractile function. This study reveals sex-specific vascular dysfunction mediated by CETP.","PeriodicalId":73119,"journal":{"name":"Function (Oxford, England)","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11237897/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141565333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Single Cell RNAseq Analysis of Cytokine-Treated Human Islets: Association of Cellular Stress with Impaired Cytokine Responsiveness. 细胞因子处理的人类胰岛的单细胞 RNAseq 分析：细胞压力与细胞因子反应能力受损的关系

IF 5.1

Function (Oxford, England) Pub Date : 2024-07-11 DOI: 10.1093/function/zqae015

Jennifer S Stancill, Moujtaba Y Kasmani, Weiguo Cui, John A Corbett

{"title":"Single Cell RNAseq Analysis of Cytokine-Treated Human Islets: Association of Cellular Stress with Impaired Cytokine Responsiveness.","authors":"Jennifer S Stancill, Moujtaba Y Kasmani, Weiguo Cui, John A Corbett","doi":"10.1093/function/zqae015","DOIUrl":"10.1093/function/zqae015","url":null,"abstract":"Pancreatic β-cells are essential for survival, being the only cell type capable of insulin secretion. While they are believed to be vulnerable to damage by inflammatory cytokines such as interleukin-1 beta (IL-1β) and interferon-gamma, we have recently identified physiological roles for cytokine signaling in rodent β-cells that include the stimulation of antiviral and antimicrobial gene expression and the inhibition of viral replication. In this study, we examine cytokine-stimulated changes in gene expression in human islets using single-cell RNA sequencing. Surprisingly, the global responses of human islets to cytokine exposure were remarkably blunted compared to our previous observations in the mouse. The small population of human islet cells that were cytokine responsive exhibited increased expression of IL-1β-stimulated antiviral guanylate-binding proteins, just like in the mouse. Most human islet cells were not responsive to cytokines, and this lack of responsiveness was associated with high expression of genes encoding ribosomal proteins. We further correlated the expression levels of RPL5 with stress response genes, and when expressed at high levels, RPL5 is predictive of failure to respond to cytokines in all endocrine cells. We postulate that donor causes of death and isolation methodologies may contribute to stress of the islet preparation. Our findings indicate that activation of stress responses in human islets limits cytokine-stimulated gene expression, and we urge caution in the evaluation of studies that have examined cytokine-stimulated gene expression in human islets without evaluation of stress-related gene expression.","PeriodicalId":73119,"journal":{"name":"Function (Oxford, England)","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11237896/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141565334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0