title: Dynamic changes of mitochondrial fusion and fission proteins after transient cerebral ischemia in mice.
abstract: With fusion or fission, mitochondria alter their morphology in response to various physiological and pathological stimuli, resulting in elongated, tubular, interconnected, or fragmented forms. Immunohistochemistry and Western blot analysis were performed at 2 days, 7 days, 14 days, and 28 days after 90 min of transient middle cerebral artery occlusion (tMCAO) in mice. This study showed that mitochondrial fission protein dynamin-related protein 1 (Drp1) and fusion protein optic atrophy 1 (Opa1) were both upregulated in the ischemic penumbra, with the peak at 2 days after tMCAO, whereas phosphorylated-Drp1 (P-Drp1) progressively increased with a peak at 14 days after tMCAO. Double-immunofluorescence analysis showed many Drp1/cytochrome c oxidase subunit l (COX1) double-positive cells and Opa1/COX1 double-positive cells in the ischemic penumbra and also showed some double-positive cells with Drp1/terminal deoxynucleotidyl transferase-mediated dUTP-digoxigenin nick end labeling (TUNEL) and Opa1/TUNEL in the ischemic penumbra. In contrast, both Drp1 and Opa1 showed progressive decreases until 2 days after tMCAO in the ischemic core because of necrotic brain damage. The present study suggests that there was a continuous mitochondrial fission and fusion during these periods in the ischemic penumbra after tMCAO, probably in an effort toward mitophagy and cellular survival.
authors.affiliation: Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan.
authors.forename: Wentao
authors.initials: W
authors.lastname: Liu
authors.forename: Fengfeng
authors.initials: F
authors.lastname: Tian
authors.forename: Tomoko
authors.initials: T
authors.lastname: Kurata
authors.forename: Nobutoshi
authors.initials: N
authors.lastname: Morimoto
authors.forename: Koji
authors.initials: K
authors.lastname: Abe
mesh_terms: D000818:Animals; D051545:Cyclooxygenase 1 / Q000378:metabolism; D004195:Disease Models, Animal; D034281:Dynamins / Q000235:genetics / Q000378:metabolism*; D020558:GTP Phosphohydrolases / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology; D020287:In Situ Nick-End Labeling / Q000379:methods; D002546:Ischemic Attack, Transient / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D008928:Mitochondria / Q000378:metabolism*; D013997:Time Factors; D014404:Tubulin / Q000378:metabolism
chemical_list: D008565:Membrane Proteins; D014404:Tubulin; D051545:Cyclooxygenase 1; C496512:Ptgs1 protein, mouse; D020558:GTP Phosphohydrolases; C498809:Opa1 protein, mouse; C486391:Dnm1l protein, mouse; D034281:Dynamins