• Journal of Animal Reproduction and Biotechnology
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• v.36 no.3
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• pp.145-153
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• 2021

The role of transient receptor potential vanilloid receptor-1 (TRPV1) has been primarily investigated in pain sensory neurons. Relatively, little research has been performed in testicular cells. TRPV1 is abundantly expressed in Leydig cells of young adult mice. This study was conducted to determine the role of the TRPV1 channel in Leydig cells. TRPV1 modulators and testosterone were treated to the mouse Leydig cell line TM3 cells for 24 h. Capsaicin, a TRPV1 activator, dose-dependently induced cell death, whereas capsazepine, a TRPV1 inhibitor, inhibited capsaicin-induced cell death. Testosterone treatment reduced capsaicin-induced cell death. High concentrations of testosterone decreased TRPV1 mRNA and protein expression levels. However, TRPV1 modulators did not affect testosterone production. These results showed that capsaicin induced cell death of Leydig cells and that testosterone reduced capsaicin-induced cell death. Our findings suggest that testosterone may regulate the survival of Leydig cells in young adult mice by decreasing the expression level of TRPV1.

• The Korean Journal of Physiology and Pharmacology
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• v.16 no.3
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• pp.211-217
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• 2012

Recent studies have demonstrated that nitric oxide (NO) activates transient receptor potential vanilloid subtype 1 (TRPV1) via S-nitrosylation of the channel protein. NO also modulates various cellular functions via activation of the soluble guanylyl cyclase (sGC)/protein kinase G (PKG) pathway and the direct modification of proteins. Thus, in the present study, we investigated whether NO could indirectly modulate the activity of TRPV1 via a cGMP/PKG-dependent pathway in cultured rat dorsal root ganglion (DRG) neurons. NO donors, sodium nitroprusside (SNP) and S-nitro-N-acetylpenicillamine (SNAP), decreased capsaicin-evoked currents ($I_{cap}$). NO scavengers, hemoglobin and 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (CPTIO), prevented the inhibitory effect of SNP on $I_{cap}$. Membrane-permeable cGMP analogs, 8-bromoguanosine 3', 5'-cyclic monophosphate (8bromo-cGMP) and 8-(4chlorophenylthio)-guanosine 3',5'-cyclic monophosphate (8-pCPT-cGMP), and the guanylyl cyclase stimulator YC-1 mimicked the effect of SNP on $I_{cap}$. The PKG inhibitor KT5823 prevented the inhibition of $I_{cap}$ by SNP. These results suggest that NO can downregulate the function of TRPV1 through activation of the cGMP/PKG pathway in peripheral sensory neurons.

• Yonsei Medical Journal
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• v.59 no.9
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• pp.1131-1137
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• 2018

Purpose: Previous reports have shown that hyperglycemia-induced inhibition of transient receptor potential vanilloid sub type 4 (TRPV4), a transient receptor potential ion channel, affects the severity of hearing impairment (HI). In this study, we explored the role of TRPV4 in HI using HEI-OC1 cells exposed to high glucose (HG). Materials and Methods: HEI-OC1 cells were cultured in a HG environment (25 mM D-glucose) for 48 hours, and qRT-PCR and Western blotting were used to analyze the expression of TRPV4 at the mRNA and protein level. TRPV4 agonist (GSK1016790A) or antagonist (HC-067047) in cultured HEI-OC1 cells was used to obtain abnormal TRPV4 expression. Functional TRPV4 activity was assessed in cultured HEI-OC1 cells using the MTT assay and a cell death detection ELISA. Results: TRPV4 agonists exerted protective effects against HG-induced HI, as evidenced by increased MTT levels and inhibition of apoptosis in HEI-OC1 cells. TRPV4 overexpression significantly increased protein levels of phosphorylated p38 mitogen-activated protein kinase (p-p38 MAPK), while TRPV4 antagonists had the opposite effect. Our results indicated that TRPV4 is a hyperglycemia-related factor that can inhibit cell proliferation and promote cell apoptosis by activating the MAPK signaling pathway in HEI-OC1 cells. Conclusion: Our results show that the overexpression of TRPV4 can attenuate cell death in HEI-OC1 cells exposed to HG.

• International Journal of Oral Biology
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• v.40 no.4
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• pp.183-187
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• 2015

The present study was aimed to evaluate the influence of glutaraldehyde (GA) concentration on multiple electron microscopic (EM) immunostaining using pre-embedding peroxidase and post-embedding immunogold method. Influence of various concentrations of GA included in the fixative on immuoreactivity was assessed in the multiple immunostaining using antisera against anti-transient receptor potential vanilloid 1 (TRPV1) for peroxidase staining and anti-GABA for immunogold labeling in the rat trigeminal caudal nucleus. Anti-TRPV1 antiserum had specificity in pre-embedding peroxidase staining when tissues were fixed with fixative containing paraformaldehyde (PFA) alone. Immunoreactivity for TRPV1 was specific in tissues fixed with fixative containing 0.5% GA at both perfusion and postfixation steps, though the immunoreactivity was weaker than in tissues fixed with fixative containing PFA alone. Tissues fixed with fixative containing 0.5% GA at the perfusion and postfixation steps showed specific immunogold staining for GABA. The results of the present study indicate that GA concentration is critical for immunoreactivity to antigens such as TRPV1 and GABA. This study also suggests that the appropriate GA concentration is 0.5% for multiple immunostaining with peroxidase labeling for TRPV1 and immunogold labeling for GABA.

• Annals of dermatology
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• v.30 no.6
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• pp.653-661
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• 2018

Background: Citron is well known for an abundance of antioxidative and anti-inflammatory ingredients such as vitamin C, polyphenol compounds, flavonoids, and limonoids. Objective: In this study, we aimed to evaluate the effects of citron essential oils on rosacea mediators in activated keratinocytes in vitro. Methods: Normal human epidermal keratinocytes (NHEKs) were stimulated with $1{\alpha}$, 25-dihydroxyvitamin $D_3$ ($VD_3$) and interleukin 33 (IL-33) with LL-37 to induce rosacea mediators such as kallikrein 5 (KLK5), cathelicidin, vascular endothelial growth factor (VEGF), and transient receptor potential vanilloid 1 (TRPV1). These mediators were analyzed by performing reverse-transcription polymerase chain reaction (PCR), quantitative real-time PCR, immunocytofluorescence and enzyme-linked immunosorbent assay after NHEKs were treated with citron seed and unripe citron essential oils. Results: The messenger RNA (mRNA) and protein levels of KLK5 and LL-37 induced by $VD_3$ were suppressed by citron seed and unripe citron essential oils. Furthermore, the mRNA and protein levels of VEGF and TRPV1 induced by IL-33 with LL-37 were also suppressed by citron essential oils. Conclusion: These results show that citron essential oils have suppressive effects on rosacea mediators in activated epidermal keratinocytes, which indicates that the citron essential oils may be valuable adjuvant therapeutic agents for rosacea.

• The Korean Journal of Physiology and Pharmacology
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• v.20 no.1
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• pp.129-136
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• 2016

This study was performed to investigate whether an intra-articular injection of transient receptor potential vanilloid 1 (TRPV1) receptor agonist, resiniferatoxin (RTX) would alleviate behavioral signs of arthritic pain in a rat model of osteoarthritis (OA). We also sought to determine the effect of RTX treatment on calcitonin gene-related peptide (CGRP) expression in the spinal cord. Knee joint inflammation was induced by intra-articular injection of monosodium iodoacetate (MIA, $8mg/50{\mu}l$) and weight bearing percentage on right and left hindpaws during walking, paw withdrawal threshold to mechanical stimulation, and paw withdrawal latency to heat were measured to evaluate pain behavior. Intra-articular administration of RTX (0.03, 0.003 and 0.0003%) at 2 weeks after the induction of knee joint inflammation significantly improved reduction of weight bearing on the ipsilateral hindlimb and increased paw withdrawal sensitivity to mechanical and heat stimuli. The reduction of pain behavior persisted for 3~10 days according to each behavioral test. The MIA-induced increase in CGRP immunoreactivity in the spinal cord was decreased by RTX treatment in a dose-dependent manner. The present study demonstrated that a single intra-articular administration of RTX reduced pain behaviors for a relatively long time in an experimental model of OA and could normalize OA-associated changes in peptide expression in the spinal cord.

• Korean Journal of Exercise Nutrition
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• v.24 no.3
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• pp.39-43
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• 2020

[Purpose] In this literature review we aimed to investigate the effects of curcumin supplementation on delayed onset muscle soreness (DOMS), which occurs after exercise, and evaluate related parameters to propose practical recommendations for the field of exercise physiology. [Methods] Experimental studies conducted on curcumin supplementation and DOMS were systematically reviewed to determine (1) the effect of curcumin supplementation on DOMS, (2) potential mechanisms by which curcumin supplementation may attenuate DOMS, and (3) practical considerations for curcumin supplementation. [Results] While several studies have reported that curcumin supplementation attenuates DOMS after exercise, others have reported that curcumin supplementation has no effect on DOMS. Several mechanisms have been proposed by which curcumin supplementation may attenuate DOMS; the most probable of which is a reduction in inflammatory response. Other potential mechanisms include modulation of transient receptor potential vanilloid 1 (TRPV1) or changes in post-exercise capillary lactate levels; these require further examination. The usual recommended dose of curcumin is 150-1500 mg daily (sometimes up to 5 g), divided into 2-3 portions and taken before and after exercise. It is not necessary to take curcumin together with piperine. [Conclusion] Although conflicting results regarding the effects of curcumin supplementation on DOMS exist in literature, it may be considered as a method of nutritional intervention for reducing post-exercise DOMS.

• The Korean Journal of Physiology and Pharmacology
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• v.22 no.3
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• pp.225-234
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• 2018

Adenosine is a naturally occurring breakdown product of adenosine triphosphate and plays an important role in different physiological and pathological conditions. Adenosine also serves as an important trigger in ischemic and remote preconditioning and its release may impart cardioprotection. Exogenous administration of adenosine in the form of adenosine preconditioning may also protect heart from ischemia-reperfusion injury. Endogenous release of adenosine during ischemic/remote preconditioning or exogenous adenosine during pharmacological preconditioning activates adenosine receptors to activate plethora of mechanisms, which either independently or in association with one another may confer cardioprotection during ischemia-reperfusion injury. These mechanisms include activation of $K_{ATP}$ channels, an increase in the levels of antioxidant enzymes, functional interaction with opioid receptors; increase in nitric oxide production; decrease in inflammation; activation of transient receptor potential vanilloid (TRPV) channels; activation of kinases such as protein kinase B (Akt), protein kinase C, tyrosine kinase, mitogen activated protein (MAP) kinases such as ERK 1/2, p38 MAP kinases and MAP kinase kinase (MEK 1) MMP. The present review discusses the role and mechanisms involved in adenosine preconditioning-induced cardioprotection.

• Archives of Pharmacal Research
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• v.28 no.1
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• pp.73-80
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• 2005

The effect of capsaicin on apoptotic cell death was investigated in HepG2 human hepatoma cells. Capsaicin induced apoptosis in time- and dose-dependent manners. Capsaicin induced a rapid and sustained increase in intracellular $Ca^{2+}$ concentration, and BAPTA, an intracellular $Ca^{2+}$ chelator, significantly inhibited capsaicin-induced apoptosis. The capsaicin-induced increase in the intracellular $Ca^{2+}$ and apoptosis were not significantly affected by the extracellular $Ca^{2+}$ chelation with EGTA, whereas blockers of intracellular $Ca^{2+}$ release (dantrolene) and phospholipase C inhibitors, U-73122 and manoalide, profoundly reduced the capsaicin effects. Interestingly, treatment with the vanilloid receptor antagonist, capsazepine, did not inhibit either the increased capsaicin-induced $Ca^{2+}$ or apoptosis. Collectively, these results suggest that the capsaicin-induced apoptosis in the HepG2 cells may result from the activation of a PLC-dependent intracellular $Ca^{2+}$ release pathway, and it is further suggested that capsaicin may be valuable for the therapeutic intervention of human hepatomas.

• The Korean Journal of Physiology and Pharmacology
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• v.18 no.6
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• pp.525-530
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• 2014

Transient receptor potential vanilloid subtype 1 (TRPV1) was originally found in sensory neurons. Recently, it has been reported that TRPV1 is expressed in salivary gland epithelial cells (SGEC). However, the physiological role of TRPV1 in salivary secretion remains to be elucidated. We found that TRPV1 is expressed in mouse and human submandibular glands (SMG) and HSG cells, originated from human submandibular gland ducts at both mRNA and protein levels. However, capsaicin (CAP), TRPV1 agonist, had little effect on intracellular free calcium concentration ($[Ca^{2+}]_i$) in these cells, although carbachol consistently increased $[Ca^{2+}]_i$. Exposure of cells to high temperature (> $43^{\circ}C$) or acidic bath solution (pH5.4) did not increase $[Ca^{2+}]_i$, either. We further examined the role of TRPV1 in salivary secretion using TRPV1 knock-out mice. There was no significant difference in the pilocarpine (PILO)-induced salivary flow rate between wild-type and TRPV1 knock-out mice. Saliva flow rate also showed insignificant change in the mice treated with PILO plus CAP compared with that in mice treated with PILO alone. Taken together, our results suggest that although TRPV1 is expressed in SGEC, it appears not to play any direct roles in saliva secretion via transcellular pathway.