Cytochrome c binds to inositol (1,4,5) trisphosphate and ryanodine receptors in vivo after transient brain ischemia in gerbils.
Previously we have shown that the biphasic efflux of mitochondrial protein cytochrome c to cytoplasm is one of the important events of the delayed postichemic neuronal death. We concluded that early and transient appearance of cytochrome c in cytoplasm of cells recovering after ischemia was decisive for initiation of the pathological signaling cascade leading to neuronal death, but the precise mechanism remained unknown. In vitro cytochrome c was identified as a messenger that coordinates mitochondrial-endoplasmatic reticulum interactions that drive apoptosis. Here we show that in vivo cytochrome c interacts with inositol (1,4,5) trisphosphate receptor type 1 in gerbil hippocampus subjected to transient brain ischemia and short reperfusion. Moreover, cytochrome c binds also to ryanodine receptor type 2, the role of which in postischemic neuronal death is suggested. The complexes could be coimmunoprecipitated by antibodies against any of the two proteins. Our data verified that the mechanism observed in vitro applies to the pathological in vivo situation.
Beresewicz
Małgorzata
M
Molecular Biology Unit, Mossakowski Medical Research Centre, PAS, 5 Pawińskiego, 02-106 Warsaw, Poland.
Kowalczyk
Joanna E
JE
Zabłocka
Barbara
B
D000818:Animals; D016893:Carotid Stenosis / Q000150:complications; D016923:Cell Death; D045304:Cytochromes c / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005849:Gerbillinae; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism*; D002546:Ischemic Attack, Transient / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D009474:Neurons / Q000473:pathology; D011485:Protein Binding; D021381:Protein Transport; D015424:Reperfusion; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism*
D019837:Ryanodine Receptor Calcium Release Channel; D015544:Inositol 1,4,5-Trisphosphate; D045304:Cytochromes c