首页|Endoplasmic reticulum stress caused by traumatic injury promotes cardiomyocyte apoptosis through acetylation modification of GRP78
Endoplasmic reticulum stress caused by traumatic injury promotes cardiomyocyte apoptosis through acetylation modification of GRP78
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Cardiomyocyte apoptosis is an important cause of trauma-induced secondary cardiac injury(TISCI),in which the endoplasmic reticulum stress(ERS)-mediated apoptosis signaling pathway is known to be first activated,but the mechanism remains unclear.In this study,rat models of traumatic injury are established by using the Noble-Collip trauma device.The expression of glucose-regulating protein 78(GRP78,a molecular chaperone of the cardio-myocyte ER),acetylation modification of GRP78 and apoptosis of cardiomyocytes are determined.The results show that ERS-induced GRP78 elevation does not induce cardiomyocyte apoptosis in the early stage of trauma.However,with prolonged ERS,the GRP78 acetylation level is elevated,and the apoptosis of cardiomyocytes also increases significantly.In addition,in the early stage of trauma,the expression of histone acetyl-transferase(HAT)P300 is increased and that of histone deacetylase 6(HDAC6)is decreased in cardiomyocytes.Inhibition of HDAC function could induce the apoptosis of traumatic cardiomyocytes by increasing the acetylation level of GRP78.Our present study demonstrates for the first time that post-traumatic protracted ERS can promote cardiomyocyte apoptosis by increasing the acetylation level of GRP78,which may provide an experimental basis for seeking early molecular events of TISCI.
acetylationapoptosiscardiomyocytesGRP78trauma
Zi Yan、Yufeng Liu、Bowen Yang、Wenhui Zhao、Yan Wang、Deping Wang、Jianguo Li、Xiangying Jiao、Jimin Cao
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Department of Physiology,Shanxi Medical University,Taiyuan 030001,China
State Key Laboratory of Cellular Physiology,Shanxi Medical University,Taiyuan 030001,China
the First Clinical Medical College,Shanxi Medical University,Taiyuan 030001,China
Guangdong Province Key Laboratory of Psychiatric Disorders,Guangzhou 510515,China
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国家自然科学基金Basic Research Program of Shanxi ProvinceBasic Research Program of Shanxi Province山西省"1331工程"重点学科建设项目Research Grant of Guangdong Province Key Laboratory of Psychiatric Disorders
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