title: Simulated microgravity-induced mitochondrial dysfunction in rat cerebral arteries.
abstract: Exposure to microgravity results in cardiovascular deconditioning, and cerebrovascular oxidative stress injury has been suggested to occur. To elucidate the mechanism for this condition, we investigated whether simulated microgravity induces mitochondrial dysfunction in rat arteries. Four-week hindlimb unweighting (HU) was used to simulate microgravity in rats. Mitochondrial reactive oxygen species (ROS), mitochondrial membrane potential (Δψm), mitochondrial permeability transition pore (mPTP) opening, mitochondrial respiratory control ratio (RCR), MnSOD/GPx activity and expression, and mitochondrial malondialdehyde (MDA) were examined in rat cerebral and mesenteric VSMCs. Compared with the control rats, mitochondrial ROS levels, mPTP opening, and MDA content increased significantly (P<0.001, P<0.01, and P<0.01, respectively), Δψm, RCR, MnSOD/GPx activity (P<0.001 for Δψm and RCR; P<0.05 for MnSOD; and P<0.001 for GPx activity) and protein abundance of mitochondrial MnSOD/GPx-1 decreased (P<0.001 for MnSOD and GPx-1) in HU rat cerebral but not mesenteric arteries. Chronic treatment with NADPH oxidase inhibitor apocynin and mitochondria-targeted antioxidant mitoTempol promoted recovery of mitochondrial function in HU rat cerebral arteries, but exerted no effects on HU rat mesenteric arteries. Therefore, simulated microgravity resulted in cerebrovascular mitochondrial dysfunction, and crosstalk between NADPH oxidase and mitochondria participated in the process.
authors.affiliation: Institute of Geriatric Cardiology.
authors.forename: Ran
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Department of Geriatric Hematology.
authors.forename: Hai-Hong
authors.initials: HH
authors.lastname: Ran
authors.affiliation: Department of Clinical Laboratory Medicine, and.
authors.forename: Li-Li
authors.initials: LL
authors.lastname: Cai
authors.affiliation: Changhai Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Institute of Geriatric Cardiology.
authors.forename: Jun-Fang
authors.initials: JF
authors.lastname: Sun
authors.affiliation: Institute of Geriatric Cardiology.
authors.forename: Liang
authors.initials: L
authors.lastname: Peng
authors.affiliation: Institute of Geriatric Cardiology.
authors.forename: Xiao-Juan
authors.initials: XJ
authors.lastname: Liu
authors.affiliation: Institute of Geriatric Cardiology.
authors.forename: Lan-Ning
authors.initials: LN
authors.lastname: Zhang
authors.affiliation: Institute of Geriatric Cardiology.
authors.forename: Zhou
authors.initials: Z
authors.lastname: Fang
authors.affiliation: Institute of Geriatric Cardiology.
authors.forename: Yong-Yan
authors.initials: YY
authors.lastname: Fan
authors.affiliation: Department of Osteology, Chinese People's Liberation Army General Hospital, Beijing, China; and bjzhangran@126.com.
authors.forename: Geng
authors.initials: G
authors.lastname: Cui
mesh_terms: D000098:Acetophenones / Q000494:pharmacology; D000818:Animals; D002536:Cerebral Arteries / Q000503:physiopathology* / Q000648:ultrastructure; D005979:Glutathione Peroxidase / Q000378:metabolism; D019417:Hindlimb Suspension; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000502:physiology; D008638:Mesenteric Arteries / Q000648:ultrastructure; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism; D000083162:Mitochondrial Permeability Transition Pore; D019255:NADPH Oxidases / Q000378:metabolism; D009943:Organophosphorus Compounds / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D018474:Weightlessness Simulation / Q000009:adverse effects*
chemical_list: D000098:Acetophenones; C555916:MitoTEMPO; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D009943:Organophosphorus Compounds; D010880:Piperidines; D017382:Reactive Oxygen Species; C056165:acetovanillone; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D019255:NADPH Oxidases
keywords: NADPH oxidase; hindlimb unweighting; oxidative stress