Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0003129 (Anoxia)
 551 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

How cells die in the absence of oxygen (anoxia) is not understood. Here we report that cells deficient in Bax and Bak or caspase-9 do not undergo anoxia-induced cell death. However, the caspase-9 null cells do not survive reoxygenation due to the generation of mitochondrial reactive oxygen species. The individual loss of Bim, Bid, Puma, Noxa, Bad, caspase-2, or hypoxia-inducible factor 1beta, which are potential upstream regulators of Bax or Bak, did not prevent anoxia-induced cell death. Anoxia triggered the loss of the Mcl-1 protein upstream of Bax/Bak activation. Cells containing a mitochondrial DNA cytochrome b 4-base-pair deletion ([rho(-)] cells) and cells depleted of their entire mitochondrial DNA ([rho(0)] cells) are oxidative phosphorylation incompetent and displayed loss of the Mcl-1 protein under anoxia. [rho(0)] cells, in contrast to [rho(-)] cells, did not die under anoxia. However, [rho(0)] cells did undergo cell death in the presence of the Bad BH3 peptide, an inhibitor of Bcl-X(L)/Bcl-2 proteins. These results indicate that [rho(0)] cells survive under anoxia despite the loss of Mcl-1 protein due to residual prosurvival activity of the Bcl-X(L)/Bcl-2 proteins. Collectively, these results demonstrate that anoxia-induced cell death requires the loss of Mcl-1 protein and inhibition of the electron transport chain to negate Bcl-X(L)/Bcl-2 proteins.
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PMID:Loss of Mcl-1 protein and inhibition of electron transport chain together induce anoxic cell death. 1714 74

Anoxia, the condition of oxygen deprivation, induces apoptosis via the intrinsic apoptotic pathway. Cells deficient in both Bax and Bak do not undergo cell death during anoxia. However, the underlying mechanism of anoxia induced cell death is not well defined. Here we report our latest findings of two critical events that are required to induce cell death during anoxia. First, a key member of the Bcl-2 family of pro-survival proteins, Mcl-1, undergoes proteasomal-dependent degradation. The loss of Mcl-1 protein is independent of Bax or Bak indicating this is an early event in the apoptotic cascade. Second, cells inhibit the mitochondrial electron transport chain to negate the pro-survival function of Bcl-2/Bcl-X(L). These observations indicate that loss of pro-survival function is necessary for anoxia induced cell death.
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PMID:Role of Bcl-2 family members in anoxia induced cell death. 1737