TY - JOUR
T1 - Dynamic changes of mitochondrial fusion and fission proteins after transient cerebral ischemia in mice
AU - Liu, Wentao
AU - Tian, Fengfeng
AU - Kurata, Tomoko
AU - Morimoto, Nobutoshi
AU - Abe, Koji
PY - 2012/6
Y1 - 2012/6
N2 - 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.
AB - 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.
KW - Drp1
KW - Fission
KW - Fusion
KW - Opa1
KW - TMCAO
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UR - http://www.scopus.com/inward/citedby.url?scp=84862786010&partnerID=8YFLogxK
U2 - 10.1002/jnr.23016
DO - 10.1002/jnr.23016
M3 - Article
C2 - 22345048
AN - SCOPUS:84862786010
VL - 90
SP - 1183
EP - 1189
JO - Journal of Neuroscience Research
JF - Journal of Neuroscience Research
SN - 0360-4012
IS - 6
ER -