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The impact of α-Lipoic acid on cell viability and expression of nephrin and ZNF580 in normal human podocytes.

Abstract：

:Human podocytes (hPC) are essential for maintaining normal kidney function and dysfunction or loss of hPC play a pivotal role in the manifestation and progression of chronic kidney diseases including diabetic nephropathy. Previously, α-Lipoic acid (α-LA), a licensed drug for treatment of diabetic neuropathy, was shown to exhibit protective effects on diabetic nephropathy in vivo. However, the effect of α-LA on hPC under non-diabetic conditions is unknown. Therefore, we analyzed the impact of α-LA on cell viability and expression of nephrin and zinc finger protein 580 (ZNF580) in normal hPC in vitro. Protein analyses were done via Western blot techniques. Cell viability was determined using a functional assay. hPC viability was dynamically modulated via α-LA stimulation in a concentration-dependent manner. This was associated with reduced nephrin and ZNF580 expression and increased nephrin phosphorylation in normal hPC. Moreover, α-LA reduced nephrin and ZNF580 protein expression via 'kappa-light-chain-enhancer' of activated B-cells (NF-κB) inhibition. These data demonstrate that low α-LA had no negative influence on hPC viability, whereas, high α-LA concentrations induced cytotoxic effects on normal hPC and reduced nephrin and ZNF580 expression via NF-κB inhibition. These data provide first novel information about potential cytotoxic effects of α-LA on hPC under non-diabetic conditions.

journal_name

Eur J Pharmacol

journal_title

European journal of pharmacology

authors

Leppert U,Gillespie A,Orphal M,Böhme K,Plum C,Nagorsen K,Berkholz J,Kreutz R,Eisenreich A

doi

10.1016/j.ejphar.2017.06.013

subject

Has Abstract

pub_date

2017-09-05 00:00:00

pages

1-8

eissn

0014-2999

issn

1879-0712

pii

S0014-2999(17)30408-9

journal_volume

810

pub_type

杂志文章

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