Adenovirus-mediated overexpression of SOAT1 attenuates 7-ketocholesterol-induced cytotoxicity and inflammation in ARPE-19 cells

Monday, September 22, 2014 — Poster Session II
4:00 p.m. – 6:00 p.m.	FAES Academic Center	NEI	MOLBIO-13

Authors

• J.W. Lee
• I.R Rodriguez

Abstract

7-Ketocholesterol (7KCh) is known to have potent pro-inflammatory and cytotoxic effects in cultured RPE cells. Our previous study has shown that the only significant metabolism of 7KCh in ARPE-19 cells is by esterification to membrane fatty acids catalyzed by sterol O-acyltransferase (SOAT1). In this study, we investigated whether adenovirus-mediated overexpression of SOAT1 can attenuate 7KCh-induced cytotoxicity and inflammation in ARPE-19 cells. Adenovirus SOAT1 infection resulted in a high level of SOAT1 protein overexpression in ARPE-19 cells. In normal ARPE-19 cells 4 main 7KCh-fatty acid esters (7KFAEs) are formed which account for 20% of the internalized 7KCh 24 h after 7KCh treatment. SOAT1 overexpression increased 7KFAEs synthesis by 1.5-fold and reduced intracellular 7KCh levels by 40%. SOAT1 overexpression significantly decreased the levels of IL-6 and IL-8 protein in conditioned media but had no effect on VEGF levels. SOAT1 overexpression protected the cells from 7KCh-induced cytotoxicity. These results suggest that overexpression of SOAT1 in ARPE-19 cells attenuates 7KCh-induced cell toxicity and inflammation. This effect is likely due to the increased conversion of 7KCh to 7KFAEs which reduced the intracellular 7KCh levels. This seems to be the only metabolic pathway available to extra-hepatic tissues.

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