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

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, alpha-Lipoic acid (alpha-LA), a licensed drug for treatment of diabetic neuropathy, was shown to exhibit protective effects on diabetic nephropathy in vivo. However, the effect of alpha-LA on hPC under non-diabetic conditions is unknown. Therefore, we analyzed the impact of alpha-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 alpha-LA stimulation in a concentration-dependent manner. This was associated with reduced nephrin and ZNF580 expression and increased nephrin phosphorylation in normal hPC. Moreover, alpha-LA reduced nephrin and ZNF580 protein expression via 'kappa-light-chain-enhancer' of activated B-cells (NF-kappa B) inhibition. These data demonstrate that low alpha-LA had no negative influence on hPC viability, whereas, high alpha-LA concentrations induced cytotoxic effects on normal hPC and reduced nephrin and ZNF580 expression via NF-kappa B inhibition. These data provide first novel information about potential cytotoxic effects of alpha-LA on hPC under non-diabetic conditions.