Essential Roles of S-Nitrosothiols in Vascular Homeostasis and Endotoxic Shock

Limin Liu, Yun Yan, Ming Zeng, Jian Zhang, Martha A. Hanes, Gregory Ahearn, Timothy J. McMahon, Timm Dickfeld, Harvey E. Marshall, Loretta G. Que, Jonathan S. Stamler

Research output: Contribution to journalArticle

Abstract

The current perspective of NO biology is formulated predominantly from studies of NO synthesis. The role of S-nitrosothiol (SNO) formation and turnover in governing NO-related bioactivity remains uncertain. We generated mice with a targeted gene deletion of S-nitrosoglutathione reductase (GSNOR), and show that they exhibit substantial increases in whole-cell S-nitrosylation, tissue damage, and mortality following endotoxic or bacterial challenge. Further, GSNOR-/- mice have increased basal levels of SNOs in red blood cells and are hypotensive under anesthesia. Thus, SNOs regulate innate immune and vascular function, and are cleared actively to ameliorate nitrosative stress. Nitrosylation of cysteine thiols is a critical mechanism of NO function in both health and disease.

Original languageEnglish (US)
Pages (from-to)617-628
Number of pages12
JournalCell
Volume116
Issue number4
DOIs
StatePublished - Feb 20 2004
Externally publishedYes

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Fingerprint Dive into the research topics of 'Essential Roles of S-Nitrosothiols in Vascular Homeostasis and Endotoxic Shock'. Together they form a unique fingerprint.

  • Cite this

    Liu, L., Yan, Y., Zeng, M., Zhang, J., Hanes, M. A., Ahearn, G., McMahon, T. J., Dickfeld, T., Marshall, H. E., Que, L. G., & Stamler, J. S. (2004). Essential Roles of S-Nitrosothiols in Vascular Homeostasis and Endotoxic Shock. Cell, 116(4), 617-628. https://doi.org/10.1016/S0092-8674(04)00131-X