High glucose and diabetes enhanced store-operated Ca2+ entry and increased expression of its signaling proteins in mesangial cells

Sarika Chaudhari, Peiwen Wu, Yanxia Wang, Yanfeng Ding, Joseph P. Yuan, Malcolm Begg, Rong Ma

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28 Citations (Scopus)

Abstract

The present study was conducted to determine whether and how store-operated Ca2+ entry (SOCE) in glomerular mesangial cells (MCs) was altered by high glucose (HG) and diabetes. Human MCs were treated with either normal glucose or HG for different time periods. Cyclopiazonic acid-induced SOCE was significantly greater in the MCs with 7-day HG treatment and the response was completely abolished by GSK- 7975A, a selective inhibitor of store-operated Ca2+ channels. Similarly, the inositol 1,4,5-trisphosphate-induced store-operated Ca2+ currents were significantly enhanced in the MCs treated with HG for 7 days, and the enhanced response was abolished by both GSK-7975A and La3+. In contrast, receptor-operated Ca2+ entry in MCs was significantly reduced by HG treatment. Western blotting showed that HG increased the expression levels of STIM1 and Orai1 in cultured MCs. A significant HG effect occurred at a concentration as low as 10 mM, but required a minimum of 7 days. The HG effect in cultured MCs was recapitulated in renal glomeruli/cortex of both type I and II diabetic rats. Furthermore, quantitative real-time RT-PCR revealed that a 6-day HG treatment significantly increased the mRNA expression level of STIM1. However, the expressions of STIM2 and Orai1 transcripts were not affected by HG. Taken together, these results suggest that HG/diabetes enhanced SOCE in MCs by increasing STIM1/Orai1 protein expressions. HG upregulates STIM1 by promoting its transcription but increases Orai1 protein through a posttranscriptional mechanism.

Original languageEnglish
JournalAmerican Journal of Physiology - Renal Physiology
Volume306
Issue number9
DOIs
StatePublished - 1 May 2014

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Mesangial Cells
Glucose
Proteins
Cultured Cells
Inositol 1,4,5-Trisphosphate
Real-Time Polymerase Chain Reaction
Up-Regulation

Keywords

  • Diabetic nephropathy
  • High glucose
  • Mesangial cells
  • Orai1
  • STIM1

Cite this

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title = "High glucose and diabetes enhanced store-operated Ca2+ entry and increased expression of its signaling proteins in mesangial cells",
abstract = "The present study was conducted to determine whether and how store-operated Ca2+ entry (SOCE) in glomerular mesangial cells (MCs) was altered by high glucose (HG) and diabetes. Human MCs were treated with either normal glucose or HG for different time periods. Cyclopiazonic acid-induced SOCE was significantly greater in the MCs with 7-day HG treatment and the response was completely abolished by GSK- 7975A, a selective inhibitor of store-operated Ca2+ channels. Similarly, the inositol 1,4,5-trisphosphate-induced store-operated Ca2+ currents were significantly enhanced in the MCs treated with HG for 7 days, and the enhanced response was abolished by both GSK-7975A and La3+. In contrast, receptor-operated Ca2+ entry in MCs was significantly reduced by HG treatment. Western blotting showed that HG increased the expression levels of STIM1 and Orai1 in cultured MCs. A significant HG effect occurred at a concentration as low as 10 mM, but required a minimum of 7 days. The HG effect in cultured MCs was recapitulated in renal glomeruli/cortex of both type I and II diabetic rats. Furthermore, quantitative real-time RT-PCR revealed that a 6-day HG treatment significantly increased the mRNA expression level of STIM1. However, the expressions of STIM2 and Orai1 transcripts were not affected by HG. Taken together, these results suggest that HG/diabetes enhanced SOCE in MCs by increasing STIM1/Orai1 protein expressions. HG upregulates STIM1 by promoting its transcription but increases Orai1 protein through a posttranscriptional mechanism.",
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High glucose and diabetes enhanced store-operated Ca2+ entry and increased expression of its signaling proteins in mesangial cells. / Chaudhari, Sarika; Wu, Peiwen; Wang, Yanxia; Ding, Yanfeng; Yuan, Joseph P.; Begg, Malcolm; Ma, Rong.

In: American Journal of Physiology - Renal Physiology, Vol. 306, No. 9, 01.05.2014.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - High glucose and diabetes enhanced store-operated Ca2+ entry and increased expression of its signaling proteins in mesangial cells

AU - Chaudhari, Sarika

AU - Wu, Peiwen

AU - Wang, Yanxia

AU - Ding, Yanfeng

AU - Yuan, Joseph P.

AU - Begg, Malcolm

AU - Ma, Rong

PY - 2014/5/1

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N2 - The present study was conducted to determine whether and how store-operated Ca2+ entry (SOCE) in glomerular mesangial cells (MCs) was altered by high glucose (HG) and diabetes. Human MCs were treated with either normal glucose or HG for different time periods. Cyclopiazonic acid-induced SOCE was significantly greater in the MCs with 7-day HG treatment and the response was completely abolished by GSK- 7975A, a selective inhibitor of store-operated Ca2+ channels. Similarly, the inositol 1,4,5-trisphosphate-induced store-operated Ca2+ currents were significantly enhanced in the MCs treated with HG for 7 days, and the enhanced response was abolished by both GSK-7975A and La3+. In contrast, receptor-operated Ca2+ entry in MCs was significantly reduced by HG treatment. Western blotting showed that HG increased the expression levels of STIM1 and Orai1 in cultured MCs. A significant HG effect occurred at a concentration as low as 10 mM, but required a minimum of 7 days. The HG effect in cultured MCs was recapitulated in renal glomeruli/cortex of both type I and II diabetic rats. Furthermore, quantitative real-time RT-PCR revealed that a 6-day HG treatment significantly increased the mRNA expression level of STIM1. However, the expressions of STIM2 and Orai1 transcripts were not affected by HG. Taken together, these results suggest that HG/diabetes enhanced SOCE in MCs by increasing STIM1/Orai1 protein expressions. HG upregulates STIM1 by promoting its transcription but increases Orai1 protein through a posttranscriptional mechanism.

AB - The present study was conducted to determine whether and how store-operated Ca2+ entry (SOCE) in glomerular mesangial cells (MCs) was altered by high glucose (HG) and diabetes. Human MCs were treated with either normal glucose or HG for different time periods. Cyclopiazonic acid-induced SOCE was significantly greater in the MCs with 7-day HG treatment and the response was completely abolished by GSK- 7975A, a selective inhibitor of store-operated Ca2+ channels. Similarly, the inositol 1,4,5-trisphosphate-induced store-operated Ca2+ currents were significantly enhanced in the MCs treated with HG for 7 days, and the enhanced response was abolished by both GSK-7975A and La3+. In contrast, receptor-operated Ca2+ entry in MCs was significantly reduced by HG treatment. Western blotting showed that HG increased the expression levels of STIM1 and Orai1 in cultured MCs. A significant HG effect occurred at a concentration as low as 10 mM, but required a minimum of 7 days. The HG effect in cultured MCs was recapitulated in renal glomeruli/cortex of both type I and II diabetic rats. Furthermore, quantitative real-time RT-PCR revealed that a 6-day HG treatment significantly increased the mRNA expression level of STIM1. However, the expressions of STIM2 and Orai1 transcripts were not affected by HG. Taken together, these results suggest that HG/diabetes enhanced SOCE in MCs by increasing STIM1/Orai1 protein expressions. HG upregulates STIM1 by promoting its transcription but increases Orai1 protein through a posttranscriptional mechanism.

KW - Diabetic nephropathy

KW - High glucose

KW - Mesangial cells

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U2 - 10.1152/ajprenal.00463.2013

DO - 10.1152/ajprenal.00463.2013

M3 - Article

VL - 306

JO - American Journal of Physiology - Renal Physiology

JF - American Journal of Physiology - Renal Physiology

SN - 0363-6127

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