Mitochondrial Oxidative Stress Enhances Vasoconstriction by Altering Calcium Homeostasis in Cerebrovascular Smooth Muscle Cells under Simulated Microgravity  

作　　者：LIU Zi Fan WANG Hai Ming JIANG Min WANG Lin LIN Le Jian ZHAO Yun Zhang SHAO Jun Jie ZHOU Jing Jing XIE Man Jiang LI Xin ZHANG Ran 

机构地区：[1]Department of Cardiovascular Medicine,Chinese PLA General Hospital&Chinese PLA Medical School,Beijing 100853,China [2]Department of Cardiology,The Eighth Medical Center of Chinese PLA General Hospital,Beijing 100193,China [3]The First Clinical Medical College of Inner Mongolia Medical University,Hohhot 010059,Inner Mongolia,China [4]Department of Aerospace Physiology,Key Laboratory of Aerospace Medicine of Ministry of Education,Fourth Military Medical University,Xi'an 710032,Shaanxi,China [5]Division of Health services,The First Medical Center of Chinese PLA General Hospital,Beijing 100853,China

出　　处：《Biomedical and Environmental Sciences》2021年第3期203-212,共10页生物医学与环境科学（英文版）

基　　金：supported by the National Natural Science Foundation of China[81871516,81571841];Youth Special Project of Chinese PLA General Hospital[QNC19052]。

摘　　要：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(IP3 R)abundance,and the activities of voltage-gated K+channels(KV)and Ca^(2+)-activated K+channels(BKCa)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 IP3 R protein/mRNA levels were significantly upregulated.The current densities and open probabilities of KV and BKCa 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 IP3 R expression levels and restored the activities of the KV and BKCa 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.

关 键 词：MICROGRAVITY Mitochondrial oxidative stress Calcium homeostasis VASOCONSTRICTION 

分 类 号：R852.22[医药卫生—航空、航天与航海医学]