Format

Send to

Choose Destination
Eur J Pharmacol. 2017 Sep 5;810:1-8. doi: 10.1016/j.ejphar.2017.06.013. Epub 2017 Jun 10.

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

Author information

1
Charité-Universitätsmedizin Berlin, CC02, Institut für Physiologie, Berlin, Germany.
2
Charité-Universitätsmedizin Berlin, CC04, Institut für Klinische Pharmakologie und Toxikologie, Berlin, Germany.
3
Charité-Universitätsmedizin Berlin, CC04, Institut für Klinische Pharmakologie und Toxikologie, Berlin, Germany. Electronic address: andreas.eisenreich@charite.de.

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.

KEYWORDS:

Human podocytes; Nephrin; ZNF580; α-lipoic acid

PMID:
28606850
DOI:
10.1016/j.ejphar.2017.06.013
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center