Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.


Sci. STKE, 16 November 2004
Vol. 2004, Issue 259, p. tw414
[DOI: 10.1126/stke.2592004tw414]

EDITORS' CHOICE

CARDIOPHYSIOLOGY NOS Serves to Prevent Oxidative Stress

Xanthine oxidoreductase (XOR), an enzyme involved in purine metabolism, produces superoxide (O2•—), highly reactive oxygen species that may contribute to heart failure. Khan et al. report that XOR and nitric oxide synthase 1 (NOS1), but not NOS3, coimmunoprecipitate and are colocalized in the sarcoplasmic reticulum of mouse cardiac myocytes. Based on measurements of superoxide production from hearts from NOS1—/— and wild-type mice, deficiency in NOS1 causes an increase in superoxide production, which was inhibited by addition of the XOR inhibitor allopurinol. Under conditions of oxidative stress (high-frequency stimulation), the myocytes from NOS1—/— mice lacked the increase in myocyte contraction observed in the wild-type myocytes, and this effect was reversed by treatment with allopurinol. Thus, it appears that NOS1 specifically serves to inhibit XOR-mediated oxidative stress to regulate cardiocyte contractility. Although not investigated here, there are several mechanisms by which NO may inhibit oxidative stress caused by XOR-produced superoxide: direct inhibition of XOR activity by NO, or scavenging of superoxide by NO.

S. A. Khan, K. Lee, K. M. Minhas, D. R. Gonzalez, S. V. Y. Raju, A. D. Tejani, D. Li, D. E. Berkowitz, J. M. Hare, Neuronal nitric oxide synthase negatively regulates xanthine oxidoreductase inhibition of cardiac excitation-contraction coupling. Proc. Natl. Acad. Sci. U.S.A. 101, 15944-15948 (2004). [Abstract] [Full Text]

Citation: NOS Serves to Prevent Oxidative Stress. Sci. STKE 2004, tw414 (2004).


To Advertise     Find Products


Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882