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Tytuł:
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Mitochondrial Oxidative Stress Enhances Vasoconstriction by Altering Calcium Homeostasis in Cerebrovascular Smooth Muscle Cells under Simulated Microgravity.
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Autorzy:
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Liu ZF; Department of Cardiovascular Medicine, Chinese PLA General Hospital & Chinese PLA Medical School, Beijing 100853, China.
Wang HM; Department of Cardiovascular Medicine, Chinese PLA General Hospital & Chinese PLA Medical School, Beijing 100853, China.
Jiang M; Department of Cardiovascular Medicine, Chinese PLA General Hospital & Chinese PLA Medical School, Beijing 100853, China.
Wang L; Department of Cardiovascular Medicine, Chinese PLA General Hospital & Chinese PLA Medical School, Beijing 100853, China.
Lin LJ; Department of Cardiology, The Eighth Medical Center of Chinese PLA General Hospital, Beijing 100193, China.
Zhao YZ; Department of Cardiovascular Medicine, Chinese PLA General Hospital & Chinese PLA Medical School, Beijing 100853, China.
Shao JJ; The First Clinical Medical College of Inner Mongolia Medical University, Hohhot 010059, Inner Mongolia, China.
Zhou JJ; Department of Cardiovascular Medicine, Chinese PLA General Hospital & Chinese PLA Medical School, Beijing 100853, China.
Xie MJ; Department of Aerospace Physiology, Key Laboratory of Aerospace Medicine of Ministry of Education, Fourth Military Medical University, Xi'an 710032, Shaanxi, China.
Li X; Division of Health services, The First Medical Center of Chinese PLA General Hospital, Beijing 100853, China.
Zhang R; Department of Cardiovascular Medicine, Chinese PLA General Hospital & Chinese PLA Medical School, Beijing 100853, China.
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Źródło:
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Biomedical and environmental sciences : BES [Biomed Environ Sci] 2021 Mar 20; Vol. 34 (3), pp. 203-212.
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Typ publikacji:
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Journal Article
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Język:
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English
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Imprint Name(s):
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Publication: [Beijing, China] : Chinese Center for Disease Control and Prevention
Original Publication: Duluth, MN : Academic Press, [c1988-
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MeSH Terms:
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Homeostasis*
Oxidative Stress*
Weightlessness Simulation*
Calcium/*metabolism
Mitochondria/*physiology
Myocytes, Smooth Muscle/*physiology
Vasoconstriction/*physiology
Animals ; Cerebral Arteries ; Male ; Rats ; Rats, Sprague-Dawley
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Contributed Indexing:
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Keywords: Calcium homeostasis; Microgravity; Mitochondrial oxidative stress; Vasoconstriction
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Substance Nomenclature:
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SY7Q814VUP (Calcium)
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Entry Date(s):
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Date Created: 20210326 Date Completed: 20210406 Latest Revision: 20220421
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Update Code:
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20240105
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DOI:
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10.3967/bes2021.001
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PMID:
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33766216
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Objective: Exposure to microgravity results in postflight cardiovascular deconditioning in astronauts. Vascular oxidative stress injury and mitochondrial dysfunction have been reported during this process. To elucidate the mechanism for this condition, we investigated whether mitochondrial oxidative stress regulates calcium homeostasis and vasoconstriction in hindlimb unweighted (HU) rat cerebral arteries.
Methods: Three-week HU was used to simulate microgravity in rats. The contractile responses to vasoconstrictors, mitochondrial fission/fusion, Ca 2+ distribution, inositol 1,4,5-trisphosphate receptor (IP 3 R) abundance, and the activities of voltage-gated K + channels (K V ) and Ca 2+ -activated K + channels (BK Ca ) were examined in rat cerebral vascular smooth muscle cells (VSMCs).
Results: An increase of cytoplasmic Ca 2+ and a decrease of mitochondrial/sarcoplasmic reticulum (SR) Ca 2+ were observed in HU rat cerebral VSMCs. The abundance of fusion proteins (mitofusin 1/2 [MFN1/2]) and fission proteins (dynamin-related protein 1 [DRP1] and fission-mitochondrial 1 [FIS1]) was significantly downregulated and upregulated, respectively in HU rat cerebral VSMCs. The cerebrovascular contractile responses to vasoconstrictors were enhanced in HU rats compared to control rats, and IP 3 R protein/mRNA levels were significantly upregulated. The current densities and open probabilities of K V and BK Ca decreased and increased, respectively. Treatment with the mitochondrial-targeted antioxidant mitoTEMPO attenuated mitochondrial fission by upregulating MFN1/2 and downregulating DRP1/FIS1. It also decreased IP 3 R expression levels and restored the activities of the K V and BK Ca channels. MitoTEMPO restored the Ca 2+ distribution in VSMCs and attenuated the enhanced vasoconstriction in HU rat cerebral arteries.
Conclusion: The present results suggest that mitochondrial oxidative stress enhances cerebral vasoconstriction by regulating calcium homeostasis during simulated microgravity.
(Copyright © 2020 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.)
