Send to

Choose Destination
See comment in PubMed Commons below
Cancer Lett. 2005 Aug 8;226(1):1-15. Epub 2004 Dec 8.

Nitric oxide as a modulator of apoptosis.

Author information

Biological Engineering Division and Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Ave., Room 26-009, Cambridge, MA 02139, USA.


Unphysiologically high levels of nitric oxide (NO*) are mutagenic and may contribute to carcinogenesis. Proapoptotic and anitiapoptotic functions of NO* have been reported in various in vivo and in vitro experimental models. The complexity of biological responses induced is a consequence of the multiple chemical pathways through which NO* causes damage to critical cellular macromolecules. The extent and kinetics of apoptotic and other responses are highly dependent on steady-state NO* levels, cumulative total dose and cell type. Steady-state and total dose thresholds have been defined, both of which must be exceeded for the induction of apoptosis and other responses in human lymphoblastoid cells. DNA damage, protein modifications, p53 activation and mitochondrial respiratory inhibition contribute to NO*-mediated apoptosis via mitochondrial and Fas receptor pathways. Multifaceted cellular defense systems including glutathione, antioxidant enzymes and Nrf2-Keap1 signaling participate in protective responses to mitigate damage by toxic levels of NO*.

[Indexed for MEDLINE]
PubMed Commons home

PubMed Commons

How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science
    Loading ...
    Support Center