Guangbi Li, Dandan Huang, Pengyang Li, Xinxu Yuan, Viktor Yarotskyy, Pin-Lan Li
{"title":"Regulation of exosome release by lysosomal acid ceramidase in coronary arterial endothelial cells: Role of TRPML1 channel.","authors":"Guangbi Li, Dandan Huang, Pengyang Li, Xinxu Yuan, Viktor Yarotskyy, Pin-Lan Li","doi":"10.1016/bs.ctm.2022.09.002","DOIUrl":"https://doi.org/10.1016/bs.ctm.2022.09.002","url":null,"abstract":"<p><p>Lysosomal acid ceramidase (AC) has been reported to determine multivesicular body (MVB) fate and exosome secretion in different mammalian cells including coronary arterial endothelial cells (CAECs). However, this AC-mediated regulation of exosome release from CAECs and associated underlying mechanism remain poorly understood. In the present study, we hypothesized that AC controls lysosomal Ca<sup>2+</sup> release through TRPML1 channel to regulate exosome release in murine CAECs. To test this hypothesis, we isolated and cultured CAECs from WT/WT and endothelial cell-specific Asah1 gene (gene encoding AC) knockout mice. Using these CAECs, we first demonstrated a remarkable increase in exosome secretion and significant reduction of lysosome-MVB interaction in CAECs lacking Asah1 gene compared to those cells from WT/WT mice. ML-SA1, a TRPML1 channel agonist, was found to enhance lysosome trafficking and increase lysosome-MVB interaction in WT/WT CAECs, but not in CAECs lacking Asah1 gene. However, sphingosine, an AC-derived sphingolipid, was able to increase lysosome movement and lysosome-MVB interaction in CAECs lacking Asah1 gene, leading to reduced exosome release from these cells. Moreover, Asah1 gene deletion was shown to substantially inhibit lysosomal Ca<sup>2+</sup> release through suppression of TRPML1 channel activity in CAECs. Sphingosine as an AC product rescued the function of TRPML1 channel in CAECs lacking Asah1 gene. These results suggest that Asah1 gene defect and associated deficiency of AC activity may inhibit TRPML1 channel activity, thereby reducing MVB degradation by lysosome and increasing exosome release from CAECs. This enhanced exosome release from CAECs may contribute to the development of coronary arterial disease under pathological conditions.</p>","PeriodicalId":11029,"journal":{"name":"Current topics in membranes","volume":"90 ","pages":"37-63"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9842397/pdf/nihms-1861805.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10057071","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Role of TRPV4 Channels in Different Organ Systems","authors":"","doi":"10.1016/s1063-5823(22)x0002-1","DOIUrl":"https://doi.org/10.1016/s1063-5823(22)x0002-1","url":null,"abstract":"","PeriodicalId":11029,"journal":{"name":"Current topics in membranes","volume":"28 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"56450567","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Endothelial TRPV4 channels in lung edema and injury.","authors":"Swapnil K Sonkusare, Victor E Laubach","doi":"10.1016/bs.ctm.2022.07.001","DOIUrl":"https://doi.org/10.1016/bs.ctm.2022.07.001","url":null,"abstract":"<p><p>The alveolo-capillary barrier is relatively impermeable, and facilitates gas exchange via the large alveolar surface in the lung. Disruption of alveolo-capillary barrier leads to accumulation of edema fluid in lung injury. Studies in animal models of various forms of lung injury provide evidence that TRPV4 channels play a critical role in disruption of the alveolo-capillary barrier and pathogenesis of lung injury. TRPV4 channels from capillary endothelial cells, alveolar epithelial cells, and immune cells have been implicated in the pathogenesis of lung injury. Recent studies in endothelium-specific TRPV4 knockout mice point to a central role for endothelial TRPV4 channels in lung injury. In this chapter, we review the findings on the pathological roles of endothelial TRPV4 channels in different forms of lung injury and future directions for further investigation.</p>","PeriodicalId":11029,"journal":{"name":"Current topics in membranes","volume":"89 ","pages":"43-62"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9744595/pdf/nihms-1853600.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9875256","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Transient receptor potential vanilloid type 4 (TRPV4) in urinary bladder structure and function.","authors":"Megan Elizabeth Perkins, Margaret A Vizzard","doi":"10.1016/bs.ctm.2022.06.002","DOIUrl":"https://doi.org/10.1016/bs.ctm.2022.06.002","url":null,"abstract":"<p><p>Bladder pain syndrome (BPS)/interstitial cystitis (IC) is a urologic, chronic pelvic pain syndrome characterized by pelvic pain, pressure, or discomfort with urinary symptoms. Symptom exacerbation (flare) is common with multiple, perceived triggers including stress. Multiple transient receptor potential (TRP) channels (TRPA1, TRPV1, TRPV4) expressed in the bladder have specific tissue distributions in the lower urinary tract (LUT) and are implicated in bladder disorders including overactive bladder (OAB) and BPS/IC. TRPV4 channels are strong candidates for mechanosensors in the urinary bladder and TRPV4 antagonists are promising therapeutic agents for OAB. In this perspective piece, we address the current knowledge of TRPV4 distribution and function in the LUT and its plasticity with injury or disease with an emphasis on BPS/IC. We review our studies that extend the knowledge of TRPV4 in urinary bladder function by focusing on (i) TRPV4 involvement in voiding dysfunction, pelvic pain, and non-voiding bladder contractions in NGF-OE mice; (ii) distention-induced luminal ATP release mechanisms and (iii) involvement of TRPV4 and vesicular release mechanisms. Finally, we review our lamina propria studies in postnatal rat studies that demonstrate: (i) the predominance of the TRPV4+ and PDGFRα+ lamina propria cellular network in early postnatal rats; (ii) the ability of exogenous mediators (i.e., ATP, TRPV4 agonist) to activate and increase the number of lamina propria cells exhibiting active Ca<sup>2+</sup> events; and (iii) the ability of ATP and TRPV4 agonist to increase the rate of integrated Ca<sup>2+</sup> activity corresponding to coupled lamina propria network events and the formation of propagating wavefronts.</p>","PeriodicalId":11029,"journal":{"name":"Current topics in membranes","volume":"89 ","pages":"95-138"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10486315/pdf/nihms-1929075.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10247788","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Olaf A Bachkoenig, Benjamin Gottschalk, Roland Malli, Wolfgang F Graier
{"title":"An unexpected effect of risperidone reveals a nonlinear relationship between cytosolic Ca<sup>2+</sup> and mitochondrial Ca<sup>2+</sup> uptake.","authors":"Olaf A Bachkoenig, Benjamin Gottschalk, Roland Malli, Wolfgang F Graier","doi":"10.1016/bs.ctm.2022.09.001","DOIUrl":"https://doi.org/10.1016/bs.ctm.2022.09.001","url":null,"abstract":"<p><p>Mitochondria actively contribute to cellular Ca<sup>2+</sup> homeostasis. The molecular mechanisms of mitochondrial Ca<sup>2+</sup> uptake and release are well characterized and are attributed to the multi-protein assembly of the mitochondrial Ca<sup>2+</sup> uniporter complex (MCUC) and the mitochondrial sodium-calcium exchanger (NCLX), respectively. Hence, Ca<sup>2+</sup> transfer from the endoplasmic reticulum (ER) and store-operated Ca<sup>2+</sup> entry (SOCE) into the mitochondrial matrix has been quantitatively visualized on the subcellular level using targeted fluorescent biosensors. However, a correlation between the amplitude of cytosolic Ca<sup>2+</sup> elevation with that in the mitochondrial matrix has not been investigated in detail so far. In the present study, we combined the Ca<sup>2+</sup>-mobilizing agonist histamine with the H<sub>1</sub>-receptor antagonist risperidone to establish a well-tunable experimental approach allowing the correlation between low, slow, high, and fast cytosolic and mitochondrial Ca<sup>2+</sup> signals in response to inositol 1,4,5-trisphosphate (IP<sub>3</sub>)-triggered ER Ca<sup>2+</sup> release. Our present data confirm a defined threshold in cytosolic Ca<sup>2+</sup>, which is necessary for the activation of mitochondrial Ca<sup>2+</sup> uptake. Moreover, our data support the hypothesis of different modes of mitochondrial Ca<sup>2+</sup> uptake depending on the source of the ion (i.e., ER vs SOCE).</p>","PeriodicalId":11029,"journal":{"name":"Current topics in membranes","volume":"90 ","pages":"13-35"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10627170","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Eric A Pereira da Silva, Miguel Martín-Aragón Baudel, Junyoung Hong, Peter Bartels, Manuel F Navedo, Madeline Nieves-Cintrón
{"title":"Vascular Ca<sub>V</sub>1.2 channels in diabetes.","authors":"Eric A Pereira da Silva, Miguel Martín-Aragón Baudel, Junyoung Hong, Peter Bartels, Manuel F Navedo, Madeline Nieves-Cintrón","doi":"10.1016/bs.ctm.2022.09.003","DOIUrl":"https://doi.org/10.1016/bs.ctm.2022.09.003","url":null,"abstract":"<p><p>Diabetic vasculopathy is a significant cause of morbidity and mortality in the diabetic population. Hyperglycemia, one of the central metabolic abnormalities in diabetes, has been associated with vascular dysfunction due to endothelial cell damage. However, studies also point toward vascular smooth muscle as a locus for hyperglycemia-induced vascular dysfunction. Emerging evidence implicates hyperglycemia-induced regulation of vascular L-type Ca<sup>2+</sup> channels Ca<sub>V</sub>1.2 as a potential mechanism for vascular dysfunction during diabetes. This chapter summarizes our current understanding of vascular Ca<sub>V</sub>1.2 channels and their regulation during physiological and hyperglycemia/diabetes conditions. We will emphasize the role of Ca<sub>V</sub>1.2 in vascular smooth muscle, the effects of elevated glucose on Ca<sub>V</sub>1.2 function, and the mechanisms underlying its dysregulation in hyperglycemia and diabetes. We conclude by examining future directions and gaps in knowledge regarding Ca<sub>V</sub>1.2 regulation in health and during diabetes.</p>","PeriodicalId":11029,"journal":{"name":"Current topics in membranes","volume":"90 ","pages":"65-93"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10627171","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"K<sup>+</sup> channels in the coronary microvasculature of the ischemic heart.","authors":"Sharanee P Sytha, Trevor S Self, Cristine L Heaps","doi":"10.1016/bs.ctm.2022.09.004","DOIUrl":"10.1016/bs.ctm.2022.09.004","url":null,"abstract":"<p><p>Ischemic heart disease is the leading cause of death and a major public health and economic burden worldwide with expectations of predicted growth in the foreseeable future. It is now recognized clinically that flow-limiting stenosis of the large coronary conduit arteries as well as microvascular dysfunction in the absence of severe stenosis can each contribute to the etiology of ischemic heart disease. The primary site of coronary vascular resistance, and control of subsequent coronary blood flow, is found in the coronary microvasculature, where small changes in radius can have profound impacts on myocardial perfusion. Basal active tone and responses to vasodilators and vasoconstrictors are paramount in the regulation of coronary blood flow and adaptations in signaling associated with ion channels are a major factor in determining alterations in vascular resistance and thereby myocardial blood flow. K<sup>+</sup> channels are of particular importance as contributors to all aspects of the regulation of arteriole resistance and control of perfusion into the myocardium because these channels dictate membrane potential, the resultant activity of voltage-gated calcium channels, and thereby, the contractile state of smooth muscle. Evidence also suggests that K<sup>+</sup> channels play a significant role in adaptations with cardiovascular disease states. In this review, we highlight our research examining the role of K<sup>+</sup> channels in ischemic heart disease and adaptations with exercise training as treatment, as well as how our findings have contributed to this area of study.</p>","PeriodicalId":11029,"journal":{"name":"Current topics in membranes","volume":"90 ","pages":"141-166"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10494550/pdf/nihms-1927820.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10572690","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Introduction to ion transport and membrane interactions in vascular health and disease.","authors":"Michael Sturek","doi":"10.1016/bs.ctm.2022.09.006","DOIUrl":"https://doi.org/10.1016/bs.ctm.2022.09.006","url":null,"abstract":"<p><p>Cardiovascular disease is on the rise, partially due to the continued increase in metabolic syndrome. Advances in basic research on vascular ion transport have the potential to provide targets for therapeutic interventions. Vascular specificity, which includes different vascular beds having different characteristics and the macro- vs. microvasculature, is a vitally important variable in characterization of ion transport. At the cellular level, targeted fluorescent biosensors for Ca<sup>2+</sup>, super-resolution microscopy, and organelle patch clamp electrophysiology enable more detailed studies. The \"MetS/diabetes milieu\" includes increased and decreased insulin, and increased glucose, increased LDL/HDL cholesterol and triglycerides, and increased blood pressure. The duration and severity of MetS/diabetes components certainly affect the vascular phenotype and ion transport and membrane interactions. A combination of in vivo animal models and in vitro cell models to study ion transport in MetS/diabetes conditions is optimal. Gene editing and selective pharmacological tools should be used after or in conjunction with characterization of ion transport in vascular health and disease phenotypes. This is critical to determining the causal role of Ca<sup>2+</sup> signaling in modulation of vascular phenotype. The ion transport and membrane interactions that are measured are typically only a snapshot in time in these dynamic processes occurring over the progression of health and disease. It is imperative that this concept be considered in the planning of long-term studies of vascular disease, ion transport experiments, and interpretation of the data. Future directions for our contributors' research will advance the field.</p>","PeriodicalId":11029,"journal":{"name":"Current topics in membranes","volume":"90 ","pages":"1-11"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10627168","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The role of TRPV4 channels in cutaneous epithelia.","authors":"Carlene Moore","doi":"10.1016/bs.ctm.2022.06.003","DOIUrl":"10.1016/bs.ctm.2022.06.003","url":null,"abstract":"<p><p>Transient receptor potential vanilloid 4 (TRPV4) channels are multi-modally activated cation permeable channels that are expressed most organ tissues including the skin. TRPV4 is highly expressed in the skin and functions in skin resident cells such as epidermal keratinocytes, melanocytes, immune mast cells and macrophages, and cutaneous neurons. TRPV4 plays many crucial roles in skin homeostasis to affect an extensive range of processes such as temperature sensation, osmo-sensation, hair growth, cell apoptosis, skin barrier integrity, differentiation, nociception and itch. Since TRPV4 functions in a plenitude of pathological states, TRPV4 can become a versatile therapeutic target for diseases such as chronic pain, itch and skin cancer.</p>","PeriodicalId":11029,"journal":{"name":"Current topics in membranes","volume":"89 ","pages":"139-154"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9990182/pdf/nihms-1875139.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10842444","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}