title: Aberrant increase in cytochrome c oxidase subunit I precedes neuronal death after cerebral ischemia.
abstract: Cerebral ischemia is known to produce excessive reactive oxygen species in mitochondria, and these radicals initiate radical chain reactions, causing cellular macromolecule damage, and also promote the mitochondrial apoptosis pathway, ultimately leading to cell death. However, little is known about the mitochondrial functional alterations after ischemia. The authors examined the expression of cytochrome c oxidase (COX), a terminal, rate-limiting enzyme of the electron transport chain to generate ATP, after global cerebral ischemia in rats. Immunofluorescent staining and western blot were performed to investigate the spatial and temporal changes in two important COX subunits: mitochondrion-encoded COX subunit I (COX I) and nucleus-encoded COX subunit IV (COX IV). Under the normal condition, these subunits have to be regulated precisely in a 1 : 1 stoichiometry to assemble the functional COX holoenzyme. In this study, a huge increase in COX I, which is disproportionate to COX IV, was observed in the early stage after lethal ischemia, preceding delayed neuronal death. In contrast, mild sublethal ischemia did not induce obvious changes in COX I and IV. This aberrant increase in COX I may be an early sign of delayed neuronal death or may predict later electron transport chain dysfunction to generate ATP.
authors.affiliation: aDepartment of Neurosurgery, Akita University School of Medicine bDepartment of Life Science, Faculty and Graduate School of Engineering and Resource Science, Akita University, Akita, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Takahashi
authors.forename: Taku
authors.initials: T
authors.lastname: Sugawara
authors.forename: Toshio
authors.initials: T
authors.lastname: Miyazaki
authors.forename: Hideaki
authors.initials: H
authors.lastname: Itoh
authors.forename: Kazuo
authors.initials: K
authors.lastname: Mizoi
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000201:enzymology* / Q000473:pathology; D056547:CA1 Region, Hippocampal / Q000201:enzymology* / Q000473:pathology; D016923:Cell Death; D003576:Electron Transport Complex IV / Q000378:metabolism*; D008297:Male; D024101:Mitochondrial Proteins / Q000378:metabolism; D017966:Pyramidal Cells / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D024101:Mitochondrial Proteins; D003576:Electron Transport Complex IV