Effects of pyrrolidine dithiocarbamate on proliferation and nuclear factor-κB activity in autosomal dominant polycystic kidney disease cells

BMC Nephrology
Michelle H T TaGopala K Rangan

Abstract

Pyrrolidine dithiocarbamate (PDTC) reduces renal cyst growth in a rodent model of polycystic kidney disease (PKD) but the mechanism of action is not clear. Here, we investigated the hypothesis that PDTC reduces the proliferation of cystic epithelial cells in vitro in a nuclear factor (NF)-κB-dependent manner. Immortalized autosomal dominant PKD (ADPKD) cells that are heterozygous (WT9-7) and homozygous (WT-9-12) for a truncating Pkd1 mutation, and immortalized normal human tubular cells (HK-2), were exposed to NF-κB-inducing agents with or without PDTC. Cell proliferation and apoptosis were assessed by bromodeoxyuridine assay and Annexin V flow cytometry, respectively. NF-κB activity was assessed by luciferase reporter assay and western blotting for nuclear p65, p50, and RelB subunits and cytoplasmic phosphorylated-IκBα. Serum-induced proliferation was similar in all cell lines over 72 h. PDTC demonstrated anti-proliferative effects that were delayed in ADPKD cells compared to HK-2. Basal NF-κB-dependent luciferase reporter activity was lower in ADPKD cells compared to normal cells. Classical NF-κB stimulants, lipopolysaccharide (LPS) and tumor necrosis factor (TNF)-α, increased NF-κB luciferase activity in HK-2, whereas in PKD...Continue Reading

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Citations

Jul 28, 2016·World Journal of Nephrology·Michelle H T TaGopala K Rangan
Sep 15, 2018·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·Caroline WeydertDjalila Mekahli
May 2, 2019·American Journal of Physiology. Renal Physiology·Sara J HolditchCharles L Edelstein
Jun 10, 2021·Drug Design, Development and Therapy·Guohu WengShixiong Huang

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Methods Mentioned

BETA
transfection
Protein Assay
nuclear translocation

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