Versatile Roles of Intracellularly Located TRPV1 Channel

Zhao, Rui; Tsang, Suk Ying

doi:10.1002/jcp.25704

Cited by 50 publications

(40 citation statements)

References 106 publications

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“…5′-Iodoresiniferatoxin (I-RTX) is an antagonist of Trpv1 38 . Trpv1 is expressed on the plasma membrane as well as intracellular membranes such as the ER and mitochondria 39 . To evaluate whether the supra-pharmacological capsaicin-induced increase in cytosolic calcium concentration is mediated by Trpv1, calcium imaging was performed in the presence of I-RTX and in the absence of extracellular calcium (Fig.…”

Section: Resultsmentioning

confidence: 99%

Supra-pharmacological concentration of capsaicin stimulates brown adipogenesis through induction of endoplasmic reticulum stress

Kida

Noguchi

Murakami

et al. 2018

Sci Rep

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We previously showed that brown (pre)adipocytes express Trpv1, a capsaicin receptor, and that capsaicin stimulates differentiation of brown preadipocytes in the late stages of brown adipogenesis. The present study revealed that treatment with 100 μM capsaicin stimulates brown adipogenesis by inducing endoplasmic reticulum (ER) stress. Treatment with capsaicin (100 μM) during brown adipogenesis enhanced lipid accumulation and the expression of Ucp1, a gene selectively expressed in brown adipocytes. Capsaicin treatment also caused an increase in the cytosolic calcium concentration even when extracellular calcium was removed. I-RTX, a Trpv1 inhibitor, did not modulate the increase in cytosolic calcium concentration, lipid accumulation or Ucp1 expression. Previous studies revealed that the release of calcium from the ER induces ER stress, leading to the conversion of X-box binding protein 1 (Xbp1) pre-mRNA to spliced Xbp1 (sXbp1) as well as the up-regulation of Chop expression. Capsaicin treatment increased the expression of sXbp1 and Chop in brown preadipocytes and did not enhance lipid accumulation or Ucp1 expression in Xbp1 knockdown cells. The present results describe a novel mechanism of brown adipogenesis regulation via ER stress that is induced by a supra-pharmacological concentration of capsaicin.

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Section: Resultsmentioning

confidence: 99%

Supra-pharmacological concentration of capsaicin stimulates brown adipogenesis through induction of endoplasmic reticulum stress

Kida

Noguchi

Murakami

et al. 2018

Sci Rep

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“…48,49 Intracellular TRPV1 expression may result from the normal trafficking of the channels to the cell surface as well as their internalization for degradation and/or recycling. 50 In addition, recent studies have suggested that these channels also may serve to regulate mitochondrial Ca 2þ uptake 51 and act as Ca 2þ release channels on the endoplasmic reticulum. 52,53 Pharmacologic inhibition of TRPV1 or TRPV4 channels caused a concentration-dependent block of retinal angiogenic sprouting in vitro.…”

Section: Discussionmentioning

confidence: 99%

Involvement of TRPV1 and TRPV4 Channels in Retinal Angiogenesis

O'Leary

McGahon

Ashraf

et al. 2019

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. We investigate the contribution of TRPV1 and TRPV4 channels to retinal angiogenesis. METHODS. Primary retinal microvascular endothelial cells (RMECs) were used for RT-PCR, Western blotting, immunolabeling, Ca 2þ signaling, and whole-cell patch-clamp studies while localization of TRPV1 also was assessed in retinal endothelial cells using whole mount preparations. The effects of pharmacologic blockers of TRPV1 and TRPV4 on retinal angiogenic activity was evaluated in vitro using sprout formation, cell migration, proliferation, and tubulogenesis assays, and in vivo using the mouse model of oxygen-induced retinopathy (OIR). Heteromultimerization of TRPV1 and TRPV4 channels in RMECs was assessed using proximity ligation assays (PLA) and electrophysiologic recording. RESULTS. TRPV1 mRNA and protein expression were identified in RMECs. TRPV1 labelling was found to be mainly localized to the cytoplasm with some areas of staining colocalizing with the plasma membrane. Staining patterns for TRPV1 were broadly similar in endothelial cells of intact vessels within retinal flat mounts. Functional expression of TRPV1 and TRPV4 in RMECs was confirmed by patch-clamp recording. Pharmacologic inhibition of TRPV1 or TRPV4 channels suppressed in vitro retinal angiogenesis through a mechanism involving the modulation of tubulogenesis. Blockade of these channels had no effect on VEGF-stimulated angiogenesis or Ca 2þ signals in vitro. PLA and patch-clamp studies revealed that TRPV1 and TRPV4 form functional heteromeric channel complexes in RMECs. Inhibition of either channel reduced retinal neovascularization and promoted physiologic revascularization of the ischemic retina in the OIR mouse model. CONCLUSIONS. TRPV1 and TRPV4 channels represent promising targets for therapeutic intervention in vasoproliferative diseases of the retina.

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“…TRPV1 is found to express on the endoplasmic reticulum/sarcoplasmic reticulum and the mitochondria 35 . Therefore, intracellular TRPV1 may control calcium level both inside the organelles and in the cytoplasm.…”

Section: Discussionmentioning

confidence: 99%

Leukocyte TRP channel gene expressions in patients with non-valvular atrial fibrillation

Düzen

Yavuz

Vuruşkan

et al. 2017

Sci Rep

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Atrial fibrillation (AF) is the most common arrhythmia in clinical practice and is a major cause of morbidity and mortality. The upregulation of TRP channels is believed to mediate the progression of electrical remodelling and the arrhythmogenesis of the diseased heart. However, there is limited data about the contribution of the TRP channels to development of AF. The aim of this study was to investigate leukocyte TRP channels gene expressions in non-valvular atrial fibrillation (NVAF) patients. The study included 47 NVAF patients and 47 sex and age matched controls. mRNA was extracted from blood samples, and real-time polymerase chain reaction was performed for gene expressions by using a dynamic array system. Low levels of TRP channel expressions in the controls were markedly potentiated in NVAF group. We observed marked increases in MCOLN1 (TRPML1), MCOLN2 (TRPML2), MCOLN3 (TRPML3), TRPA1, TRPM1, TRPM2, TRPM3, TRPM4, TRPM5, TRPM6, TRPM7, TRPM8, TRPC1, TRPC2, TRPC3, TRPC4, TRPC5, TRPC6, TRPC7, TRPV1, TRPV2, TRPV3, TRPV4, TRPV5, TRPV6, and PKD2 (TRPP2) gene expressions in NVAF patients (P < 0.05). However, there was no change in PKD1 (TRPP1) gene expression. This is the first study to provide evidence that elevated gene expressions of TRP channels are associated with the pathogenesis of NVAF.

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Versatile Roles of Intracellularly Located TRPV1 Channel

Cited by 50 publications

References 106 publications

Supra-pharmacological concentration of capsaicin stimulates brown adipogenesis through induction of endoplasmic reticulum stress

Supra-pharmacological concentration of capsaicin stimulates brown adipogenesis through induction of endoplasmic reticulum stress

Involvement of TRPV1 and TRPV4 Channels in Retinal Angiogenesis

Leukocyte TRP channel gene expressions in patients with non-valvular atrial fibrillation

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