Cargando…
TRPC1 stimulates calcium-sensing receptor-induced store-operated Ca(2+) entry and nitric oxide production in endothelial cells
Store-operated Ca(2+) entry (SOCE) via store-operated Ca(2+) channels (SOCC), encoded by transient receptor potential canonical (TRPC) channel proteins, is an important underlying mechanism regulating intracellular Ca(2+) concentration ([Ca(2+)](i)) and various intracellular functions in endothelial...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
D.A. Spandidos
2017
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5647016/ https://www.ncbi.nlm.nih.gov/pubmed/28791397 http://dx.doi.org/10.3892/mmr.2017.7164 |
_version_ | 1783272188045950976 |
---|---|
author | Qu, Yuan-Yuan Wang, La-Mei Zhong, Hua Liu, Yong-Min Tang, Na Zhu, Li-Ping He, Fang Hu, Qing-Hua |
author_facet | Qu, Yuan-Yuan Wang, La-Mei Zhong, Hua Liu, Yong-Min Tang, Na Zhu, Li-Ping He, Fang Hu, Qing-Hua |
author_sort | Qu, Yuan-Yuan |
collection | PubMed |
description | Store-operated Ca(2+) entry (SOCE) via store-operated Ca(2+) channels (SOCC), encoded by transient receptor potential canonical (TRPC) channel proteins, is an important underlying mechanism regulating intracellular Ca(2+) concentration ([Ca(2+)](i)) and various intracellular functions in endothelial cells (ECs). TRPC1, the probable candidate for SOCC, is expressed in ECs. Ca(2+)-sensing receptor (CaSR) is functionally expressed in vascular endothelium and is important in Ca(2+) mobilization and cardiovascular functions. To date, there have been no reports demonstrating an association between CaSR and TRPC1 in ECs. The present study investigated the effects of TRPC1 on CaSR-induced Ca(2+) influx and nitric oxide (NO) production in human umbilical vein ECs (HUVECs). TRPC1 and CaSR proteins in HUVECs were measured by immunostaining and western blot analysis. [Ca(2+)](i) levels were measured using the Fura-2-acetoxymethyl ester method. The indicator 3-amino, 4-aminomethyl-2, 7-difluorescein diacetate was used to measure NO production in HUVECs. The expression of TRPC1 protein in HUVECs was silenced by transfecting HUVECs with small interfering RNA (siRNA) against TRPC1. Although changes in extracellular Ca(2+) failed to alter [Ca(2+)](i) in HUVECs, the CaSR agonist spermine increased [Ca(2+)](i) and NO production in HUVECs. NO production in HUVECs was diminished in Ca(2+)-free medium or following treatment with a CaSR negative allosteric modulator (Calhex231), SOCC inhibitor (MRS1845) or TRPC inhibitor (SKF96365). The spermine-induced increases in [Ca(2+)](i) and NO production were reduced in HUVECs transfected with TRPC1 siRNA. These results suggested that TRPC1 is a primary candidate in forming SOCC that stimulates CaSR-induced SOCE and NO production in HUVECs and is a potential therapeutic target for vascular diseases. |
format | Online Article Text |
id | pubmed-5647016 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | D.A. Spandidos |
record_format | MEDLINE/PubMed |
spelling | pubmed-56470162017-10-24 TRPC1 stimulates calcium-sensing receptor-induced store-operated Ca(2+) entry and nitric oxide production in endothelial cells Qu, Yuan-Yuan Wang, La-Mei Zhong, Hua Liu, Yong-Min Tang, Na Zhu, Li-Ping He, Fang Hu, Qing-Hua Mol Med Rep Articles Store-operated Ca(2+) entry (SOCE) via store-operated Ca(2+) channels (SOCC), encoded by transient receptor potential canonical (TRPC) channel proteins, is an important underlying mechanism regulating intracellular Ca(2+) concentration ([Ca(2+)](i)) and various intracellular functions in endothelial cells (ECs). TRPC1, the probable candidate for SOCC, is expressed in ECs. Ca(2+)-sensing receptor (CaSR) is functionally expressed in vascular endothelium and is important in Ca(2+) mobilization and cardiovascular functions. To date, there have been no reports demonstrating an association between CaSR and TRPC1 in ECs. The present study investigated the effects of TRPC1 on CaSR-induced Ca(2+) influx and nitric oxide (NO) production in human umbilical vein ECs (HUVECs). TRPC1 and CaSR proteins in HUVECs were measured by immunostaining and western blot analysis. [Ca(2+)](i) levels were measured using the Fura-2-acetoxymethyl ester method. The indicator 3-amino, 4-aminomethyl-2, 7-difluorescein diacetate was used to measure NO production in HUVECs. The expression of TRPC1 protein in HUVECs was silenced by transfecting HUVECs with small interfering RNA (siRNA) against TRPC1. Although changes in extracellular Ca(2+) failed to alter [Ca(2+)](i) in HUVECs, the CaSR agonist spermine increased [Ca(2+)](i) and NO production in HUVECs. NO production in HUVECs was diminished in Ca(2+)-free medium or following treatment with a CaSR negative allosteric modulator (Calhex231), SOCC inhibitor (MRS1845) or TRPC inhibitor (SKF96365). The spermine-induced increases in [Ca(2+)](i) and NO production were reduced in HUVECs transfected with TRPC1 siRNA. These results suggested that TRPC1 is a primary candidate in forming SOCC that stimulates CaSR-induced SOCE and NO production in HUVECs and is a potential therapeutic target for vascular diseases. D.A. Spandidos 2017-10 2017-08-04 /pmc/articles/PMC5647016/ /pubmed/28791397 http://dx.doi.org/10.3892/mmr.2017.7164 Text en Copyright: © Qu et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. |
spellingShingle | Articles Qu, Yuan-Yuan Wang, La-Mei Zhong, Hua Liu, Yong-Min Tang, Na Zhu, Li-Ping He, Fang Hu, Qing-Hua TRPC1 stimulates calcium-sensing receptor-induced store-operated Ca(2+) entry and nitric oxide production in endothelial cells |
title | TRPC1 stimulates calcium-sensing receptor-induced store-operated Ca(2+) entry and nitric oxide production in endothelial cells |
title_full | TRPC1 stimulates calcium-sensing receptor-induced store-operated Ca(2+) entry and nitric oxide production in endothelial cells |
title_fullStr | TRPC1 stimulates calcium-sensing receptor-induced store-operated Ca(2+) entry and nitric oxide production in endothelial cells |
title_full_unstemmed | TRPC1 stimulates calcium-sensing receptor-induced store-operated Ca(2+) entry and nitric oxide production in endothelial cells |
title_short | TRPC1 stimulates calcium-sensing receptor-induced store-operated Ca(2+) entry and nitric oxide production in endothelial cells |
title_sort | trpc1 stimulates calcium-sensing receptor-induced store-operated ca(2+) entry and nitric oxide production in endothelial cells |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5647016/ https://www.ncbi.nlm.nih.gov/pubmed/28791397 http://dx.doi.org/10.3892/mmr.2017.7164 |
work_keys_str_mv | AT quyuanyuan trpc1stimulatescalciumsensingreceptorinducedstoreoperatedca2entryandnitricoxideproductioninendothelialcells AT wanglamei trpc1stimulatescalciumsensingreceptorinducedstoreoperatedca2entryandnitricoxideproductioninendothelialcells AT zhonghua trpc1stimulatescalciumsensingreceptorinducedstoreoperatedca2entryandnitricoxideproductioninendothelialcells AT liuyongmin trpc1stimulatescalciumsensingreceptorinducedstoreoperatedca2entryandnitricoxideproductioninendothelialcells AT tangna trpc1stimulatescalciumsensingreceptorinducedstoreoperatedca2entryandnitricoxideproductioninendothelialcells AT zhuliping trpc1stimulatescalciumsensingreceptorinducedstoreoperatedca2entryandnitricoxideproductioninendothelialcells AT hefang trpc1stimulatescalciumsensingreceptorinducedstoreoperatedca2entryandnitricoxideproductioninendothelialcells AT huqinghua trpc1stimulatescalciumsensingreceptorinducedstoreoperatedca2entryandnitricoxideproductioninendothelialcells |