ER stress mediated effects on plasma membrane cholesterol and the nitric oxide synthase activity
Mutus, B; Chaube, R
HERO ID
975883
Reference Type
Journal Article
Subtype
Abstract
Year
2008
Language
English
| HERO ID | 975883 |
|---|---|
| Material Type | Abstract |
| In Press | No |
| Year | 2008 |
| Title | ER stress mediated effects on plasma membrane cholesterol and the nitric oxide synthase activity |
| Authors | Mutus, B; Chaube, R |
| Journal | Free Radical Biology and Medicine |
| Volume | 45 |
| Issue | Suppl. |
| Page Numbers | S112-S112 |
| Abstract | 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. |
| Wosid | WOS:000260867900316 |
| Url | http://www.sciencedirect.com/science/article/pii/S089158490800628X |
| Is Certified Translation | No |
| Dupe Override | No |
| Conference Location | Indianapolis, IN |
| Conference Name | Society for Free Radical Biology and Medicine 15th Annual Meeting |
| Conference Date | November 19-23, 2008 |
| Is Public | Yes |
| Language Text | English |
| Relationship(s) |
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