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, 2 July 2002
Vol. 2002, Issue 139, p. tw228
[DOI: 10.1126/stke.2002.139.tw228]


Apoptosis NO Survival Signal

In certain situations, cells experience conflicting signals such as proapoptotic and prosurvival signals and it is the balance of two that seems to determine the cell's response. Beltrán et al. describe an example of such conflict in cells stimulated through the receptor Fas. Activation of Fas in Jurkat (human adult T cell leukemia) cells causes cells to undergo apoptosis, but the authors found that the early phases of Fas signaling actually produced a protective effect on the mitochondria. In the first hour, treatment of cells with antibody to Fas caused increased production of intracellular nitric oxide (NO). NO inhibits cytochrome oxidase (complex IV) and thus caused decreased respiration and hyperpolarization of the mitochondria. Later, after about 2 hours, a second phase occurred in which the mitochondrial membrane potential was depolarized, caspases were activated, and the cells died. The second deadly phase was accelerated if the early generation of NO was blocked with an inhibitor of NO synthase. Thus, the authors propose that the early phase response is part of a protective mechanism that is ultimately overwhelmed by the later events that cause apoptosis.

B. Beltrán, M. Quintero, E. García-Zaragozá, E. O'Connor, J. V. Esplugues, S. Moncada, Inhibition of mitochondrial respiration by endogenous nitric oxide: A critical step in Fas signaling. Proc. Natl. Acad. Sci. U.S.A. 99, 8892-8897 (2002). [Abstract] [Full Text]

Citation: NO Survival Signal. Sci. STKE 2002, tw228 (2002).

To Advertise     Find Products

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