Steroidogenic Acute Regulatory (StAR)‐Related Lipid Transfer Domain Protein 5 (STARD5) expression is associated with cholesterol content of human kidney proximal tubule cells

Abstract

STARD5 belongs to the START protein superfamily of lipid transport proteins and functions in intracellular non‐vesicular cholesterol transport. We have reported that STARD5 expression is localized to proximal tubules of mouse kidney and the objective for this study was to determine the effect of STARD5 on cholesterol efflux. Using the HK‐2 and HKC‐8 human proximal tubule cell lines, we measured 1) expression of STARD5 and the ABCA1 cholesterol efflux pump by qRT‐PCR and Western blot analysis, 2) total free cholesterol content by cholesterol oxidase assay, and 3) efflux of 3[H]‐cholesterol to the ApoA‐1 acceptor protein. Compared to HK‐2 cells, the HKC‐8 cells have 2‐fold greater STARD5 protein and an 80% increase in total free cholesterol levels. Cholesterol efflux was ~2.5‐fold more efficient in HK‐2 cells, most likely due to 3–4‐fold greater ABCA1 expression levels in this cell line. siRNA silencing of STARD5 expression resulted in a 70% increase in cholesterol efflux in HKC‐8 cells but had no effect in HK‐2 cells. Together our results support that higher expression of STARD5 may function to sequester intracellular cholesterol and impede cholesterol efflux in renal proximal tubule cells with limiting ABCA1 expression levels.