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975883 
Journal Article 
Abstract 
ER stress mediated effects on plasma membrane cholesterol and the nitric oxide synthase activity 
Mutus, B; Chaube, R 
2008 
Yes 
Free Radical Biology and Medicine
ISSN: 0891-5849
EISSN: 1873-4596 
45 
Suppl. 
S112-S112 
English 
WOS:000260867900316 
is part of a larger document 3452652 SFRBM's 15th Annual Meeting: Program and Abstracts
In a recent study in our lab we have shown that increase in plasma membrane (PM) cholesterol leads to attenuation of Nitric Oxide (NO) diffusion and NO-mediated signaling (J. Biol. Chem., Vol. 283, 18513-18521). in parallel with this study, we now have evidence that endoplasmic reticulum (ER) stress, a common occurrence in the pathology of many diseases including diabetes, cardiovascular and neurological disorders, leads to elevation in PM-cholesterol which in addition to its effects on NO-diffusion and reactivity, attenuates endothelial nitric oxide synthase (eNOS) activity and its intracellular distribution. in our attempts to discover potential pathological mechanisms that can lead to elevations in PM-cholesterol we have observed that during ER stress, neutral sphingomyelinase (NSmase) becomes dysfunctional via Snitrosation, thus disrupting the plasma membrane cholesterolsphingomyelin balance and making the plasma membrane susceptible to elevations in cholesterol levels. Furthermore, we have also observed that as the ER stress is prolonged there is an increase in the expression of Sterol Regulatory Element Binding Protein (SREBP) transcription factors upregulating cholesterol biosynthesis. These results have led us to propose a mechanism by which ER-stress can lead to endothelial dysfunction through elevation of PM-cholesterol. 
Society for Free Radical Biology and Medicine 15th Annual Meeting 
Indianapolis, IN 
November 19-23, 2008