• Home
  • Search Results
  • Rictor/mTORC2 protects against cisplatin-induced tubular cell death and acute kidney injury.

Rictor/mTORC2 protects against cisplatin-induced tubular cell death and acute kidney injury.

Kidney international (2014-01-24)
Jianzhong Li, Zhuo Xu, Lei Jiang, Junhua Mao, Zhifeng Zeng, Li Fang, Weichun He, Weiping Yuan, Junwei Yang, Chunsun Dai
ABSTRACT

The mammalian target of rapamycin (mTOR) plays a critical role for cell growth and survival in many cell types. While substantial progress has been made in understanding the abnormal activation of mTORC1 in the pathogenesis of kidney disease, little is known about mTORC2 in kidney disease such as acute kidney injury (AKI). To study this, we generated a mouse model with tubule-specific deletion of Rictor (Tubule-Rictor-/-). The knockouts were born normal and no obvious kidney dysfunction or kidney morphologic abnormality was found within 2 months of birth. However, ablation of Rictor in the tubular cells exacerbated cisplatin-induced AKI compared to that in the control littermates. As expected, tubular cell apoptosis, Akt phosphorylation (Ser473), and autophagy were induced in the kidneys from the control littermates by cisplatin treatment. Less cell autophagy or Akt phosphorylation and more cell apoptosis in the kidneys of the knockout mice were identified compared with those in the control littermates. In NRK-52E cells in vitro, Rictor siRNA transfection sensitized cell apoptosis to cisplatin but with reduced cisplatin-induced autophagy. Metformin, an inducer of autophagy, abolished cell death induced by Rictor siRNA and cisplatin. Thus, endogenous Rictor/mTORC2 protects against cisplatin-induced AKI, probably mediated by promoting cell survival through Akt signaling activation and induction of autophagy.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Lectin from Arachis hypogaea (peanut), FITC conjugate, lyophilized powder
Sigma-Aldrich
Anti-AKT antibody produced in rabbit, affinity isolated antibody
Sigma-Aldrich
Anti-AKT antibody produced in rabbit, affinity isolated antibody
Sigma-Aldrich
Anti-phospho-AKT1 (pSer473) antibody produced in rabbit, affinity isolated antibody
Sigma-Aldrich
Anti-Caspase 3 antibody produced in rabbit, IgG fraction of antiserum, buffered aqueous solution
Sigma-Aldrich
Anti-AKT1 antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution
Sigma-Aldrich
Anti-CASP3 antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution
Sigma-Aldrich
Anti-ADGRE1 antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution
Sigma-Aldrich
Anti-phospho-Akt (pSer473) antibody produced in rabbit, affinity isolated antibody
Sigma-Aldrich
Anti-RICTOR antibody produced in rabbit, purified immunoglobulin, buffered aqueous solution
Sigma-Aldrich
Anti-AKT1 antibody produced in rabbit, affinity isolated antibody
Sigma-Aldrich
Anti-AKT antibody produced in rabbit, affinity isolated antibody
Sigma-Aldrich
Anti-AKT antibody produced in rabbit, affinity isolated antibody
Sigma-Aldrich
Anti-CASP3 antibody produced in rabbit, affinity isolated antibody
Sigma-Aldrich
Anti-Akt1 antibody produced in rabbit, affinity isolated antibody, buffered aqueous solution
Sigma-Aldrich
Anti-Rictor antibody produced in rabbit, ~1-2 μg/mL, affinity isolated antibody
Sigma-Aldrich
Anti-AKT1 (Ab-473) antibody produced in rabbit, affinity isolated antibody
Sigma-Aldrich
Anti-AKT1 (Ab-450) antibody produced in rabbit, affinity isolated antibody
Sigma-Aldrich
Anti-AKT1 (Ab-308) antibody produced in rabbit, affinity isolated antibody
Sigma-Aldrich
Monoclonal Anti-AKT1 antibody produced in mouse, clone 6D6, purified immunoglobulin, buffered aqueous solution
Sigma-Aldrich
Monoclonal Anti-AKT1 antibody produced in mouse, clone 2H1, purified immunoglobulin, buffered aqueous solution
Sigma-Aldrich
Monoclonal Anti-AKT1 antibody produced in mouse, clone 4B9, purified immunoglobulin, buffered aqueous solution
Sigma-Aldrich
Monoclonal Anti-AKT1 antibody produced in mouse, clone 6G6, purified immunoglobulin, buffered aqueous solution
Sigma-Aldrich
Anti-AKT1 antibody produced in rabbit, affinity isolated antibody
Sigma-Aldrich
Anti-CASP3 antibody produced in rabbit, IgG fraction of antiserum
Sigma-Aldrich
Anti-AKT1 (ab1) antibody produced in chicken, affinity isolated antibody, buffered aqueous solution
Sigma-Aldrich
Monoclonal Anti-AKT1 antibody produced in mouse, clone 2E11, purified immunoglobulin, buffered aqueous solution
Sigma-Aldrich
Monoclonal Anti-RICTOR antibody produced in mouse, clone 1F3, purified immunoglobulin, buffered aqueous solution
Sigma-Aldrich
Monoclonal Anti-Caspase 3 antibody produced in mouse, clone 84803.111, purified immunoglobulin, lyophilized powder
Sigma-Aldrich
Anti-phospho-PKB (pSer473) antibody produced in rabbit, IgG fraction of antiserum, buffered aqueous solution