Regulation of STIM1, store-operated Ca2+ influx, and nitric oxide generation by retinoic acid in rat mesangial cells

Wanke Zhang, Hua Meng, Zhen Hua Li, Zhenju Shu, Xiuye Ma, Bin Xian Zhang

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

It has been shown that store-operated Ca2+ influx (SOC) plays critical roles in the activation of endothelial nitric oxide (NO) synthase (eNOS) and generation of NO in endothelial cells. Recent studies indicate stromal interaction molecule 1 (STIM1) is the molecule responsible for SOC activation following Ca2+ depletion in the ER. Retinoic acids (RA) have beneficial effects in the treatment of renal diseases. The mechanism of the RA action is still largely unknown. In the current study, we used primary cultured rat mesangial cells to examine the effect of RA on SOC and STIM1. In these cells, BK caused concentration-dependent [Ca2+]i mobilization. Treatment of the cells with RA, while it had no effect on the initial peak, reduced the plateau phase of BK-mediated [Ca2+] i response, indicating the inhibition of SOC by RA. The level of STIM1 protein but not mRNA in RA-treated cells was significantly reduced. RA treatment did not affect TGF-β-mediated gradual Ca2+ influx which occurred by superoxide anion-mediated mechanism, indicating RA treatment specifically inhibited SOC in mesangial cells. RT-PCR and Western blot analysis demonstrated that eNOS was expressed in rat mesangial cells grown in media containing 11 and 30 but not 5.5 mM glucose. Downregulation of STIM1 protein and BK-induced SOC by RA treatment or STIM1 dsRNA were associated with abolished NO production. The 26S proteasome inhibitor lactacystin blocked the RA-mediated downregulation of BK-induced SOC, suggesting that ubiquitin-proteasome pathway may be involved in RA-mediated STIM1 protein downregulation in rat mesangial cells. Our data suggest that glucose-induced eNOS expression and NO production in mesangial cells may contribute to hyperfiltration in diabetes and RA may exert beneficial effects by downregulation of STIM1 and SOC in mesangial cells.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Renal Physiology
Volume292
Issue number3
DOIs
StatePublished - Mar 2007

Fingerprint

Mesangial Cells
Tretinoin
Nitric Oxide
Down-Regulation
Stromal Interaction Molecule 1
Glucose
Proteins
Proteasome Inhibitors
Nitric Oxide Synthase Type III
Proteasome Endopeptidase Complex
Ubiquitin
Superoxides
Endothelial Cells
Western Blotting

Keywords

  • Diabetes
  • eNOS
  • Glomerular hyperfiltration
  • Lactacystin
  • Proteasome
  • Protein downregulation

ASJC Scopus subject areas

  • Physiology

Cite this

Regulation of STIM1, store-operated Ca2+ influx, and nitric oxide generation by retinoic acid in rat mesangial cells. / Zhang, Wanke; Meng, Hua; Li, Zhen Hua; Shu, Zhenju; Ma, Xiuye; Zhang, Bin Xian.

In: American Journal of Physiology - Renal Physiology, Vol. 292, No. 3, 03.2007.

Research output: Contribution to journalArticle

Zhang, Wanke ; Meng, Hua ; Li, Zhen Hua ; Shu, Zhenju ; Ma, Xiuye ; Zhang, Bin Xian. / Regulation of STIM1, store-operated Ca2+ influx, and nitric oxide generation by retinoic acid in rat mesangial cells. In: American Journal of Physiology - Renal Physiology. 2007 ; Vol. 292, No. 3.
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abstract = "It has been shown that store-operated Ca2+ influx (SOC) plays critical roles in the activation of endothelial nitric oxide (NO) synthase (eNOS) and generation of NO in endothelial cells. Recent studies indicate stromal interaction molecule 1 (STIM1) is the molecule responsible for SOC activation following Ca2+ depletion in the ER. Retinoic acids (RA) have beneficial effects in the treatment of renal diseases. The mechanism of the RA action is still largely unknown. In the current study, we used primary cultured rat mesangial cells to examine the effect of RA on SOC and STIM1. In these cells, BK caused concentration-dependent [Ca2+]i mobilization. Treatment of the cells with RA, while it had no effect on the initial peak, reduced the plateau phase of BK-mediated [Ca2+] i response, indicating the inhibition of SOC by RA. The level of STIM1 protein but not mRNA in RA-treated cells was significantly reduced. RA treatment did not affect TGF-β-mediated gradual Ca2+ influx which occurred by superoxide anion-mediated mechanism, indicating RA treatment specifically inhibited SOC in mesangial cells. RT-PCR and Western blot analysis demonstrated that eNOS was expressed in rat mesangial cells grown in media containing 11 and 30 but not 5.5 mM glucose. Downregulation of STIM1 protein and BK-induced SOC by RA treatment or STIM1 dsRNA were associated with abolished NO production. The 26S proteasome inhibitor lactacystin blocked the RA-mediated downregulation of BK-induced SOC, suggesting that ubiquitin-proteasome pathway may be involved in RA-mediated STIM1 protein downregulation in rat mesangial cells. Our data suggest that glucose-induced eNOS expression and NO production in mesangial cells may contribute to hyperfiltration in diabetes and RA may exert beneficial effects by downregulation of STIM1 and SOC in mesangial cells.",
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AU - Zhang, Wanke

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AU - Li, Zhen Hua

AU - Shu, Zhenju

AU - Ma, Xiuye

AU - Zhang, Bin Xian

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AB - It has been shown that store-operated Ca2+ influx (SOC) plays critical roles in the activation of endothelial nitric oxide (NO) synthase (eNOS) and generation of NO in endothelial cells. Recent studies indicate stromal interaction molecule 1 (STIM1) is the molecule responsible for SOC activation following Ca2+ depletion in the ER. Retinoic acids (RA) have beneficial effects in the treatment of renal diseases. The mechanism of the RA action is still largely unknown. In the current study, we used primary cultured rat mesangial cells to examine the effect of RA on SOC and STIM1. In these cells, BK caused concentration-dependent [Ca2+]i mobilization. Treatment of the cells with RA, while it had no effect on the initial peak, reduced the plateau phase of BK-mediated [Ca2+] i response, indicating the inhibition of SOC by RA. The level of STIM1 protein but not mRNA in RA-treated cells was significantly reduced. RA treatment did not affect TGF-β-mediated gradual Ca2+ influx which occurred by superoxide anion-mediated mechanism, indicating RA treatment specifically inhibited SOC in mesangial cells. RT-PCR and Western blot analysis demonstrated that eNOS was expressed in rat mesangial cells grown in media containing 11 and 30 but not 5.5 mM glucose. Downregulation of STIM1 protein and BK-induced SOC by RA treatment or STIM1 dsRNA were associated with abolished NO production. The 26S proteasome inhibitor lactacystin blocked the RA-mediated downregulation of BK-induced SOC, suggesting that ubiquitin-proteasome pathway may be involved in RA-mediated STIM1 protein downregulation in rat mesangial cells. Our data suggest that glucose-induced eNOS expression and NO production in mesangial cells may contribute to hyperfiltration in diabetes and RA may exert beneficial effects by downregulation of STIM1 and SOC in mesangial cells.

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KW - Proteasome

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