title: Limb ischemic preconditioning protects endothelium from oxidative stress by enhancing nrf2 translocation and upregulating expression of antioxidases.
abstract: Remote ischemic preconditioning is often performed by limb ischemic preconditioning (LIPC), which has been demonstrated to be beneficial to various cells, including endothelial cells. The mechanisms underlying the protection have not been well clarified. The present study was designed to observe the effects of sera derived from rats after LIPC on human umbilical vein endothelial cells (HUVECs) injured by hydrogen peroxide (H2O2) -induced oxidative stress and explore the involvement of redox state in the protection. Incubation with 1 mM H2O2 for 2 h induced a significant reduction in HUVECs' viability with increased production of malondialdehyde (MDA) and reactive oxygen species (ROS). Preincubation with early preconditioning serum (EPS) or delayed preconditioning serum (DPS) derived from rats subjected to LIPC alleviated these changes. Both EPS and DPS increased the nuclear translocation of transcription factor nuclear factor E2-related factor 2 (Nrf2) and the expression of antioxidases. The protective effects of EPS and DPS were blocked neither by MEK/ERK inhibitors U0126 nor by PI3K/Akt inhibitors LY294002. In conclusion, the present study provides the evidence that LIPC protects the HUVECs from H2O2-induced injury by, at least partially, enhancement of Nrf2 translocation and upregulation of antioxidases via signaling pathways independent of MEK/ERK and PI3K/Akt.
authors.affiliation: Department of Pharmacology, Shanxi Medical University, Xinjiannanlu 56, Taiyuan, 030001, Shanxi Province, China.
authors.forename: Min
authors.initials: M
authors.lastname: Chen
authors.affiliation: Department of Pharmacology, Shanxi Medical University, Xinjiannanlu 56, Taiyuan, 030001, Shanxi Province, China.
authors.forename: Mingsheng
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, Shanxi Medical University, Xinjiannanlu 56, Taiyuan, 030001, Shanxi Province, China.
authors.forename: Xuanping
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, Shanxi Medical University, Xinjiannanlu 56, Taiyuan, 030001, Shanxi Province, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Pharmacology, Shanxi Medical University, Xinjiannanlu 56, Taiyuan, 030001, Shanxi Province, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, Shanxi Medical University, Xinjiannanlu 56, Taiyuan, 030001, Shanxi Province, China.
authors.forename: Yanying
authors.initials: Y
authors.lastname: Fan
authors.affiliation: Department of Pharmacology, Shanxi Medical University, Xinjiannanlu 56, Taiyuan, 030001, Shanxi Province, China.
authors.forename: Ruizan
authors.initials: R
authors.lastname: Shi
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D004798:Enzymes / Q000378:metabolism*; D005121:Extremities / Q000098:blood supply*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007511:Ischemia / Q000503:physiopathology*; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D018384:Oxidative Stress; D021381:Protein Transport; D051381:Rats
chemical_list: D000975:Antioxidants; D004798:Enzymes; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human