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  • Alpha-lipoic acid attenuates p-cresyl sulfate-induced renal tubular injury through suppression of apoptosis and autophagy in human proximal tubular epithelial cells.

Alpha-lipoic acid attenuates p-cresyl sulfate-induced renal tubular injury through suppression of apoptosis and autophagy in human proximal tubular epithelial cells.

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie (2019-02-25)
Jung Sun Park, Hoon In Choi, Dong-Hyun Kim, Chang Seong Kim, Eun Hui Bae, Seong Kwon Ma, Soo Wan Kim
RESUMEN

The p-cresyl sulfate accumulates in kidney disease and may be involved in renal injury. α-Lipoic acid (α-LA) acts as an antioxidant in cell injury. We investigated the effects of α-LA treatment on p-cresyl sulfate-induced renal tubular injury. p-Cresyl sulfate induced cell death, and increased Bax/Bcl-2, cleaved caspase-3, Beclin-1, and LC3BII/LC3BI in human renal proximal tubular epithelial (HK-2) cells, which was counteracted by α-LA treatment. p-Cresyl sulfate-induced apoptosis was reduced by autophagy inhibitor 3-methyladenine, and p-cresyl sulfate induced autophagy was reduced by pan-caspase inhibitor Z-VAD-FMK. Moreover, p-cresyl sulfate treatment increased the expression of ER stress proteins and decreased the expression of baculoviral IAP repeat-containing proteins 6; these effects were prevented by α-LA treatment. Apoptosis and autophagy were associated with the phosphorylation of mitogen-activated protein kinase and nuclear translocation of the nuclear factor-κB p65 subunit. Pretreatment inhibitors of p38 and JNK, and knockdown of ATF4 gene reduced apoptosis- and autophagy-related protein expressions in p-cresyl sulfate treated HK-2 cells. These results demonstrate that α-lipoic acid attenuated p-cresyl sulfate-induced cell death by suppression of apoptosis and autophagy via regulation of ER stress in HK-2 cells.