Cytochrome c release from mitochondria to the cytosol was suppressed in the ischemia-tolerance-induced hippocampal CA1 region after 5-min forebrain ischemia in gerbils.
Cytochrome c was detected by immunoblotting in the cytosolic fraction 3 h after 5-min ischemia in the non-ischemia-tolerant CA1 region in which about 96% of neurons had developed delayed neuronal death, while less cytosolic cytochrome c was detected in the ischemia-tolerance-induced CA1 region where many more neurons survived. In the immunohistochemical study using anti-non-native cytochrome c monoclonal antibody, immunoreactivity was observed throughout the cytoplasm in the non-ischemia-tolerant CA1 neurons, but not in the normal and ischemia-tolerant CA1 neurons. Then we determined whether Bcl-2, Bax, Bcl-xL and Bcl-xS, which regulate the release of cytochrome c from mitochondria, were altered in the ischemia-tolerant CA1 region. Bcl-2 and Bax were up-regulated in the ischemia-tolerant group, but Bcl-xL and Bcl-xS showed no apparent difference in their expression. These results suggest that cytochrome c release is prevented in CA1 neurons in gerbils in which ischemia-tolerance had been induced and that the altered ratio of Bcl-2 to Bax may play a part in this mechanism.
Nakatsuka
H
H
Department of Neurological Surgery, Ehime University School of Medicine, Japan. hinakats@m.ehime-u.ac.jp
Ohta
S
S
Tanaka
J
J
Toku
K
K
Kumon
Y
Y
Maeda
N
N
Sakanaka
M
M
Sakaki
S
S
D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism*; D003574:Cytochrome c Group / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D005849:Gerbillinae; D006624:Hippocampus / Q000378:metabolism* / Q000648:ultrastructure; D019194:Ischemic Preconditioning; D008297:Male; D008928:Mitochondria / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000378:metabolism*; D016548:Prosencephalon / Q000098:blood supply*; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D017966:Pyramidal Cells / Q000378:metabolism / Q000648:ultrastructure; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein
D003574:Cytochrome c Group; D009419:Nerve Tissue Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein