Original Article
Effects of Kelch-like ECH-associated protein 1/nuclear factor-E2-related factor 2/antioxidant response element signaling pathway on the regulation of mitochondrial fission in cerebral ischemia/reperfusion injury
Wang Yanan, Liu Jia, Zhang Lin, Zhao Qin, Wang Shilei
Published 2020-04-15
Cite as Int J Anesth Resus, 2020,41(04): 321-325. DOI: 10.3760/cma.j.cn321761-20190415-00001
Abstract
ObjectiveTo explore the regulation of Kelch-like ECH-associated protein 1 (Keap1)/nuclear factor-E2-related factor 2 (Nrf2)/antioxidant response element (ARE) signaling pathway on mitochondrial fission after cerebral ischemia/reperfusion (I/R) injury.
MethodsThe extracted primary hippocampal neurons of rats were divided into four groups according to the random number table method: a control group (group C), an oxygen-glucose deprivation/reperfusion group (group OGD/R), an OGD/R+Nrf2 inhibitor group (group OGD/R+N) and an OGD/R+vehicle group (group OGD/R+V). The mitochondrial morphology was observed by electron microscopy. The expression of dynamin-related protein 1 (Drp1), mitochondrial fission protein 1 (Fis1), Keap1 and Nrf2 were detected by Western blot. The nuclear translocation of Nrf2 protein was observed by immunofluorescence, and the apoptosis rate of each group was detected by flow cytometry.
ResultsCompared with group C, group OGD/R presented reduced levels of Keap1 and increased levels of nuclear Nrf2 protein, Drp1 and Fis1; through immunofluorescence, the nuclear translocation of Nrf2 was found during OGD/R, with an increased apoptosis rate (P<0.05). Compared with group OGD/R, group OGD/R + N presented reduced levels of nuclear Nrf2 and increased levels of Keap1, with an increased apoptosis rate (P<0.05). There were no significant differences in the levels of Keap1, Drp1, Fis1 and nuclear Nrf2 protein and apoptosis rates between groups OGD/R+V and OGD/R (P>0.05).
ConclusionsDuring cerebral I/R, the Keap1/Nrf2/ARE signaling pathway can regulate mitochondrial fission, reduce apoptosis and relieve brain damage.
Key words:
Brain; Ischemia/reperfusion; Kelch-like ECH-associated protein 1; Nuclear factor-E2-related factor 2; Antioxidant response element; Mitochondria
Contributor Information
Wang Yanan
Medical College, Qingdao University, Qingdao 266071, China
Liu Jia
Department of Anesthesiology, the Affiliated Hospital of Qingdao University, Qingdao 266555, China
Zhang Lin
Department of Anesthesiology, the Affiliated Hospital of Qingdao University, Qingdao 266555, China
Zhao Qin
Department of Anesthesiology, the Affiliated Hospital of Qingdao University, Qingdao 266555, China
Wang Shilei
Department of Anesthesiology, the Affiliated Hospital of Qingdao University, Qingdao 266555, China