Hypoxia sensitizes cells to nitric oxide-induced apoptosis.

Abstract

Nitric oxide (NO) can induce apoptosis in a variety of cell types. A non-toxic concentration of nitric oxide under normal oxygen conditions triggered cell death under hypoxic conditions (1.5% O(2)) in fibroblasts. Nitric oxide administered during hypoxia induced the release of cytochrome c, caspase-9 activation, and the loss of mitochondrial membrane potential followed by DNA fragmentation and lactate dehydrogenase release (markers of cell death). Bcl-X(L) protected cells from nitric oxide-induced apoptosis during hypoxia by preventing the release of cytochrome c, caspase-9 activation, and by maintaining a mitochondrial membrane potential. Murine embryonic fibroblasts from bax(-/-) bak(-/-) mice exposed to nitric oxide during hypoxia did not die, indicating that pro-apoptotic Bcl-2 family members are required for NO-induced apoptosis during hypoxia. The nitric oxide-induced cell death during hypoxia was independent of cGMP and peroxynitrite. Cells devoid of mitochondrial DNA (rho secondary-cells) lack a functional electron transport chain and were resistant to nitric oxide-induced cell death during hypoxia, suggesting that a functional electron transport chain is required for nitric oxide-induced apoptosis during hypoxia.

• Authors: Vivian Y Lee, David S McClintock, Matthew T Santore, G R Scott Budinger, Navdeep S Chandel
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 277 Issue 18 Pg. 16067-74 (May 03 2002) ISSN: 0021-9258 [Print] United States
• PMID: 11861645 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• 1-hydroxy-2-oxo-3,3-bis(2-aminoethyl)-1-triazene
• Nitric Oxide Donors
• Triazenes
• Nitric Oxide
• Deoxyglucose

Topics

• Animals
• Apoptosis (drug effects, physiology)
• Cell Hypoxia (physiology)
• Cell Line
• Deoxyglucose (pharmacology)
• Embryo, Mammalian
• Fibroblasts (cytology, drug effects, physiology)
• Fibrosarcoma
• Mice
• Nitric Oxide (pharmacology)
• Nitric Oxide Donors (pharmacology)
• Rats
• Triazenes (pharmacology)
• Tumor Cells, Cultured