Scavenger receptor BI prevents nitric oxide-induced cytotoxicity and endotoxin-induced death

Xiang An Li, Ling Guo, Reto Asmis, Mariana Nikolova-Karakashian, Eric J. Smart

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

Nitric oxide (NO)-induced oxidative stress contributes to a variety of diseases. Although numerous mechanisms have been described controlling the production of NO, the mechanisms to prevent NO-induced cytotoxicity after NO synthesis are largely unknown. Here we report that scavenger receptor BI (SR-BI) prevents NO-induced cytotoxicity. Using CHO cell lines expressing wild-type and single-site mutant SR-BI protein, we demonstrate that SR-BI prevents NO-induced cytotoxicity and that a highly conserved CXXS redox motif is required for the anti-NO cytotoxicity activity of SR-BI. Using genetically manipulated mice, we demonstrate that SR-BI-null mice have a 3- to 4-fold increase in tyrosine nitrated proteins in aorta and liver compared with wild-type littermates, indicating that expression of SR-BI prevents peroxynitrite formation in vivo. Using lipopolysacharide (LPS)-challenged mice as an in vivo model of NO-induced cytotoxicity, we found that a single dose of LPS (120 000 U/g IP) induced 90% fatality of SR-BI-null mice within 3 days, whereas all of the wild-type littermates survived (n=20), demonstrating that SR-BI is highly protective against NO cytotoxicity in vivo. Importantly, SR-BI prevents LPS-induced death without eliminating NO production, suggesting that SR-BI prevents NO-induced cytotoxicity post-NO synthesis. Our study describes a novel observation that may shed new light on the treatment of nitric oxidative stress-associated diseases, such as septic shock.

Original languageEnglish (US)
Pages (from-to)e60-e65
JournalCirculation research
Volume98
Issue number7
DOIs
StatePublished - Apr 2006

Keywords

  • Endotoxin
  • Nitric oxidative stress
  • Nitric oxide
  • Scavenger receptor BI

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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