scholarly journals Transient Receptor Potential Melastatin 4 (TRPM4) Contributes to High Salt Diet-Mediated Early-Stage Endothelial Injury

2017 ◽  
Vol 41 (2) ◽  
pp. 835-848 ◽  
Author(s):  
Xiao-Qing Ding ◽  
Tao Ban ◽  
Zeng-Yan Liu ◽  
Jie Lou ◽  
Liang-Liang Tang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Endothelial Cells ◽  
Cell Migration ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
High Salt Diet ◽  
Salt Diet ◽  
Transient Receptor Potential Melastatin ◽  
Intracellular Ros ◽  
Transient Receptor

Background/Aims: The present study investigated whether the transient receptor potential melastatin 4 (TRPM4) channel plays a role in high salt diet (HSD)-induced endothelial injuries. Methods: Western blotting and immunofluorescence were used to examine TRPM4 expression in the mesenteric endothelium of Dahl salt-sensitive (SS) rats fed a HSD. The MTT, TUNEL, and transwell assays were used to evaluate the cell viability, cell apoptosis, and cell migration, respectively, of human umbilical vein endothelial cells (HUVECs). Enzyme-linked immunosorbent assays were used to determine the concentrations of intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion protein 1 (VCAM-1), and E-selectin. Carboxy-H2DCFDA, a membrane-permeable reactive oxygen species (ROS)-sensitive fluorescent probe, was used to detect intracellular ROS levels. Results: TRPM4 was mainly expressed near the plasma membrane of mesenteric artery endothelial cells, and its expression level increased in SS hypertensive rats fed a HSD. Its protein expression was significantly upregulated upon treatment with exogenous hydrogen peroxide (H2O2) and aldosterone in cultured HUVECs. Cell viability decreased upon treatment with both agents in a concentration-dependent manner, which could be partially reversed by 9-phenanthrol, a specific TRPM4 inhibitor. Exogenous H2O2 induced apoptosis, enhanced cell migration, and increased the release of adhesion molecules, including ICAM-1, VCAM-1, and E-selectin, all of which were significantly attenuated upon treatment with 9-phenanthrol. Aldosterone and H2O2 induced the accumulation of intracellular ROS, which was significantly inhibited by 9-phenanthrol, suggesting that oxidative stress is one of the mechanisms underlying aldosterone-induced endothelial injury. Conclusions: Given the fact that oxidative stress and high levels of circulating aldosterone are present in hypertensive patients, we suggest that the upregulation of TRPM4 in the vascular endothelium may be involved in endothelial injuries caused by these stimuli.

scholarly journals Glia and TRPM2 Channels in Plasticity of Central Nervous System and Alzheimer’s Diseases

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Jing Wang ◽  
Michael F. Jackson ◽  
Yu-Feng Xie
Keyword(s):  
Oxidative Stress ◽  
Synaptic Plasticity ◽  
Glial Cells ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Synaptic Efficacy ◽  
Transient Receptor Potential Melastatin ◽  
Trpm2 Channel ◽  
Trpm2 Channels ◽  
Transient Receptor

Synaptic plasticity refers to the ability of neurons to strengthen or weaken synaptic efficacy in response to activity and is the basis for learning and memory. Glial cells communicate with neurons and in this way contribute in part to plasticity in the CNS and to the pathology of Alzheimer’s disease (AD), a neurodegenerative disease in which impaired synaptic plasticity is causally implicated. The transient receptor potential melastatin member 2 (TRPM2) channel is a nonselective Ca2+-permeable channel expressed in both glial cells (microglia and astrocytes) and neurons. Recent studies indicated that TRPM2 regulates synaptic plasticity as well as the activation of glial cells. TRPM2 also modulates oxidative stress and inflammation through interaction with glial cells. As both oxidative stress and inflammation have been implicated in AD pathology, this suggests a possible contribution of TRPM2 to disease processes. Through modulating the homeostasis of glutathione, TRPM2 is involved in the process of aging which is a risk factor of AD. These results potentially point TRPM2 channel to be involved in AD through glial cells. This review summarizes recent advances in studying the contribution of TRPM2 in health and in AD pathology, with a focus on contributions via glia cells.

scholarly journals TRPV1 Activation Attenuates High-Salt Diet-Induced Cardiac Hypertrophy and Fibrosis through PPAR-δUpregulation

PPAR Research ◽  
2014 ◽  
Vol 2014 ◽  
pp. 1-12 ◽  
Author(s):  
Feng Gao ◽  
Yi Liang ◽  
Xiang Wang ◽  
Zongshi Lu ◽  
Li Li ◽  
...  
Keyword(s):  
Cardiac Hypertrophy ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Protective Role ◽  
High Salt ◽  
Transient Receptor Potential Vanilloid ◽  
High Salt Diet ◽  
Salt Diet ◽  
Transient Receptor

High-salt diet-induced cardiac hypertrophy and fibrosis are associated with increased reactive oxygen species production. Transient receptor potential vanilloid type 1 (TRPV1), a specific receptor for capsaicin, exerts a protective role in cardiac remodeling that resulted from myocardial infarction, and peroxisome proliferation-activated receptorsδ(PPAR-δ) play an important role in metabolic myocardium remodeling. However, it remains unknown whether activation of TRPV1 could alleviate cardiac hypertrophy and fibrosis and the effect of cross-talk between TRPV1 and PPAR-δon suppressing high-salt diet-generated oxidative stress. In this study, high-salt diet-induced cardiac hypertrophy and fibrosis are characterized by significant enhancement of HW/BW%, LVEDD, and LVESD, decreased FS and EF, and increased collagen deposition. These alterations were associated with downregulation of PPAR-δ, UCP2 expression, upregulation of iNOS production, and increased oxidative/nitrotyrosine stress. These adverse effects of long-term high-salt diet were attenuated by chronic treatment with capsaicin. However, this effect of capsaicin was absent in TRPV1−/−mice on a high-salt diet. Our finding suggests that chronic dietary capsaicin consumption attenuates long-term high-salt diet-induced cardiac hypertrophy and fibrosis. This benefit effect is likely to be caused by TRPV1 mediated upregulation of PPAR-δexpression.

scholarly journals Effects of high‐salt diet and thiazide on the expression of transient receptor potential vanilloid 5

2006 ◽  
Vol 20 (5) ◽  
Author(s):  
Hye Ryoun Jang ◽  
Jay Wook Lee ◽  
Nam Ju Heo ◽  
Yun Kyu Oh ◽  
Ki Young Na ◽  
...  
Keyword(s):  
Transient Receptor Potential ◽  
Receptor Potential ◽  
High Salt ◽  
Transient Receptor Potential Vanilloid ◽  
High Salt Diet ◽  
Salt Diet ◽  
Transient Receptor

scholarly journals The Human Transient Receptor Potential Melastatin 2 Ion Channel Modulates ROS Through Nrf2

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Lei Bao ◽  
Fernanda Festa ◽  
Christopher S. Freet ◽  
John P. Lee ◽  
Iwona M. Hirschler-Laszkiewicz ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Viability ◽  
Transient Receptor Potential ◽  
Oxidant Stress ◽  
Receptor Potential ◽  
Related Factor ◽  
Wild Type ◽  
Transient Receptor Potential Melastatin ◽  
Transient Receptor ◽  
Nadh Generation

Abstract Transient receptor potential melastatin channel subfamily member 2 (TRPM2) has an essential role in protecting cell viability through modulation of oxidative stress. TRPM2 is highly expressed in cancer. When TRPM2 is inhibited, mitochondria are dysfunctional, ROS levels are increased, and cell viability is reduced. Here, the importance of NF-E2-related factor (Nrf2) in TRPM2-mediated suppression of oxidant stress was explored. In TRPM2 depleted cells, antioxidant cofactors glutathione, NADPH, and NADH were significantly reduced. Cytoplasmic and nuclear expression of Nrf2 and of IQGAP1, a modulator of Nrf2 stability regulated by intracellular calcium, were decreased. Antioxidant enzymes transcriptionally regulated by Nrf2 and involved in GSH, NADPH, and NADH generation were significantly lower including PRX1 and PRX3, GPX4, GSTP1, GCLC, and MTHFD2. The glutamine pathway leading to GSH production was suppressed, and ATP and GTP levels were impaired. Reconstitution with wild type TRPM2 or Nrf2, but not TRPM2 pore mutant E960D, rescued expression of enzymes downstream of Nrf2 and restored GSH and GTP. Cell viability, ROS, NADPH, NADH, and ATP levels were fully rescued by TRPM2 and partially by Nrf2. These data show that TRPM2 maintains cell survival following oxidative stress through modulation of antioxidant pathways and cofactors regulated by Nrf2.

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