Bcl-2 blocks loss of mitochondrial membrane potential while ICE inhibitors act at a different step during inhibition of death induced by respiratory chain inhibitors.
Bcl-2, Bcl-xL, CrmA and tetrapeptide ICE inhibitor reduce the extent of necrotic cell death induced by cyanide, which primarily damages mitochondria. Although none of them affects the drastic decrease in ATP levels induced by cyanide, Bcl-2 and Bcl-xL but not CrmA or ICE inhibitor inhibit the cyanide-induced decrease in mitochondrial membrane potential. A similar blocking effect is observed on necrotic cell death induced by other respiration inhibitors, rotenone and antimycin A, and on apoptotic cell death induced by etoposide or calcium ionophore. These results indicate that Bc1-2 and Bcl-xL protect mitochondria against the loss of function during both apoptosis and at least some forms of necrotic cell death. The ICE family proteases act at a different step other than the loss of mitochondrial membrane potential.
Shimizu
S
S
The First Department of Surgery, Osaka University Medical School, Japan.
Eguchi
Y
Y
Kamiike
W
W
Waguri
S
S
Uchiyama
Y
Y
Matsuda
H
H
Tsujimoto
Y
Y
D000255:Adenosine Triphosphate / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D000001:Calcimycin / Q000494:pharmacology; D020170:Caspase 1; D016923:Cell Death / Q000187:drug effects / Q000502:physiology*; D015687:Cell Hypoxia; D002645:Chickens / Q000235:genetics; D003546:Cysteine Endopeptidases / Q000235:genetics / Q000502:physiology; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology*; D004579:Electron Transport / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005047:Etoposide / Q000494:pharmacology; D006801:Humans; D007476:Ionophores / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000502:physiology; D008969:Molecular Sequence Data; D009336:Necrosis; D016716:PC12 Cells / Q000187:drug effects / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000502:physiology*; D019253:Proto-Oncogene Proteins c-bcl-2; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015843:Serpins / Q000235:genetics / Q000502:physiology; D012966:Sodium Cyanide / Q000633:toxicity; D059005:Topoisomerase II Inhibitors; D014162:Transfection; D014475:Uncoupling Agents / Q000494:pharmacology; D014764:Viral Proteins; D051020:bcl-X Protein
C494811:BCL2L1 protein, human; C494813:Bcl2l1 protein, rat; D015853:Cysteine Proteinase Inhibitors; D004791:Enzyme Inhibitors; D007476:Ionophores; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011993:Recombinant Fusion Proteins; D015843:Serpins; D059005:Topoisomerase II Inhibitors; D014475:Uncoupling Agents; D014764:Viral Proteins; D051020:bcl-X Protein; D000001:Calcimycin; D005047:Etoposide; D000255:Adenosine Triphosphate; C074641:interleukin-1beta-converting enzyme inhibitor; D003546:Cysteine Endopeptidases; D020170:Caspase 1; D012966:Sodium Cyanide