Activation of Ca2+-sensing receptor as a protective pathway to reduce Cadmium-induced cytotoxicity in renal proximal tubular cells

Jie Gu, Shuya Dai, Yanmin Liu, Haitao Liu, Yao Zhang, Xingqi Ji, Feng Yu, Yang Zhou, Liang Chen, Ka Fai William Tse, Chris Kong Chu Wong, Binghai Chen, Haifeng Shi

研究成果: ジャーナルへの寄稿記事

5 引用 (Scopus)

抄録

Cadmium (Cd), as an extremely toxic metal could accumulate in kidney and induce renal injury. Previous studies have proved that Cd impact on renal cell proliferation, autophagy and apoptosis, but the detoxification drugs and the functional mechanism are still in study. In this study, we used mouse renal tubular epithelial cells (mRTECs) to clarify Cd-induced toxicity and signaling pathways. Moreover, we proposed to elucidate the prevent effect of activation of Ca2+ sensing receptor (CaSR) by Calcimimetic (R-467) on Cd-induced cytotoxicity and underlying mechanisms. Cd induced intracellular Ca2+ elevation through phospholipase C-inositol 1, 4, 5-trisphosphate (PLC) followed stimulating p38 mitogen-activated protein kinases (MAPK) activation and suppressing extracellular signal-regulated kinase (ERK) activation, which leaded to increase apoptotic cell death and inhibit cell proliferation. Cd induced p38 activation also contribute to autophagic flux inhibition that aggravated Cd induced apoptosis. R-467 reinstated Cd-induced elevation of intracellular Ca2+ and apoptosis, and it also increased cell proliferation and restored autophagic flux by switching p38 to ERK pathway. The identification of the activation of CaSR-mediated protective pathway in renal cells sheds light on a possible cellular protective mechanism against Cd-induced kidney injury.

元の言語英語
記事番号1092
ジャーナルScientific reports
8
発行部数1
DOI
出版物ステータス出版済み - 12 1 2018

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Calcium-Sensing Receptors
Cadmium
Kidney
Extracellular Signal-Regulated MAP Kinases
Cell Proliferation
Apoptosis
Inositol 1,4,5-Trisphosphate
Poisons
Autophagy
Wounds and Injuries
Type C Phospholipases
p38 Mitogen-Activated Protein Kinases
Cell Death
Epithelial Cells
Metals

All Science Journal Classification (ASJC) codes

  • General

これを引用

Activation of Ca2+-sensing receptor as a protective pathway to reduce Cadmium-induced cytotoxicity in renal proximal tubular cells. / Gu, Jie; Dai, Shuya; Liu, Yanmin; Liu, Haitao; Zhang, Yao; Ji, Xingqi; Yu, Feng; Zhou, Yang; Chen, Liang; Tse, Ka Fai William; Wong, Chris Kong Chu; Chen, Binghai; Shi, Haifeng.

:: Scientific reports, 巻 8, 番号 1, 1092, 01.12.2018.

研究成果: ジャーナルへの寄稿記事

Gu, J, Dai, S, Liu, Y, Liu, H, Zhang, Y, Ji, X, Yu, F, Zhou, Y, Chen, L, Tse, KFW, Wong, CKC, Chen, B & Shi, H 2018, 'Activation of Ca2+-sensing receptor as a protective pathway to reduce Cadmium-induced cytotoxicity in renal proximal tubular cells', Scientific reports, 巻. 8, 番号 1, 1092. https://doi.org/10.1038/s41598-018-19327-9
Gu, Jie ; Dai, Shuya ; Liu, Yanmin ; Liu, Haitao ; Zhang, Yao ; Ji, Xingqi ; Yu, Feng ; Zhou, Yang ; Chen, Liang ; Tse, Ka Fai William ; Wong, Chris Kong Chu ; Chen, Binghai ; Shi, Haifeng. / Activation of Ca2+-sensing receptor as a protective pathway to reduce Cadmium-induced cytotoxicity in renal proximal tubular cells. :: Scientific reports. 2018 ; 巻 8, 番号 1.
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abstract = "Cadmium (Cd), as an extremely toxic metal could accumulate in kidney and induce renal injury. Previous studies have proved that Cd impact on renal cell proliferation, autophagy and apoptosis, but the detoxification drugs and the functional mechanism are still in study. In this study, we used mouse renal tubular epithelial cells (mRTECs) to clarify Cd-induced toxicity and signaling pathways. Moreover, we proposed to elucidate the prevent effect of activation of Ca2+ sensing receptor (CaSR) by Calcimimetic (R-467) on Cd-induced cytotoxicity and underlying mechanisms. Cd induced intracellular Ca2+ elevation through phospholipase C-inositol 1, 4, 5-trisphosphate (PLC) followed stimulating p38 mitogen-activated protein kinases (MAPK) activation and suppressing extracellular signal-regulated kinase (ERK) activation, which leaded to increase apoptotic cell death and inhibit cell proliferation. Cd induced p38 activation also contribute to autophagic flux inhibition that aggravated Cd induced apoptosis. R-467 reinstated Cd-induced elevation of intracellular Ca2+ and apoptosis, and it also increased cell proliferation and restored autophagic flux by switching p38 to ERK pathway. The identification of the activation of CaSR-mediated protective pathway in renal cells sheds light on a possible cellular protective mechanism against Cd-induced kidney injury.",
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AU - Zhou, Yang

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