TY - JOUR
T1 - Hypoxia sensitizes cells to nitric oxide-induced apoptosis
AU - Lee, Vivian Y.
AU - McClintock, David S.
AU - Santore, Matthew T.
AU - Scott Budinger, G. R.
AU - Chandel, Navdeep S.
PY - 2002/5/3
Y1 - 2002/5/3
N2 - 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% O2) 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-XL 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 (p°-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.
AB - 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% O2) 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-XL 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 (p°-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.
UR - http://www.scopus.com/inward/record.url?scp=0037013299&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0037013299&partnerID=8YFLogxK
U2 - 10.1074/jbc.M111177200
DO - 10.1074/jbc.M111177200
M3 - Article
C2 - 11861645
AN - SCOPUS:0037013299
SN - 0021-9258
VL - 277
SP - 16067
EP - 16074
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 18
ER -