Geranylgeranylacetone-induced heat shock protein70 expression reduces retinal ischemia-reperfusion injury through PI3K/AKT/mTOR signaling

作者全名："Zhang, Lirong; Xue, Kaige; Fan, Ping; Chen, Chunyan; Hu, Jiaheng; Huang, Juan; Lu, Weitian; Xu, Jin; Xu, Shiye; Ran, Jianhua; Zhu, Shujuan; Gan, Shengwei"

作者地址："[Zhang, Lirong; Xue, Kaige; Chen, Chunyan; Hu, Jiaheng; Huang, Juan; Lu, Weitian; Xu, Jin; Xu, Shiye; Ran, Jianhua; Zhu, Shujuan; Gan, Shengwei] Basic Med Coll Chongqing Med Univ, Inst Neurosci, Chongqing, Peoples R China; [Fan, Ping] Fifth Peoples Hosp Chongqing, Dept Gynecol & Obstet, Chongqing, Peoples R China; [Gan, Shengwei] Basic Med Coll Chongqing Med Univ, Inst Neurosci, 1, Med Coll Rd, Chongqing, Peoples R China"

通信作者："Gan, SW (通讯作者)，Basic Med Coll Chongqing Med Univ, Inst Neurosci, 1, Med Coll Rd, Chongqing, Peoples R China."

来源：EXPERIMENTAL EYE RESEARCH

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:000944620500001

JCR分区：Q1

影响因子：3

年份：2023

卷号：229

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Heat shock protein 70; Apoptosis; Autophagy; Gliosis; Retinal ischemia-reperfusion injury

摘要："Retinal ischemia-reperfusion (I/R) injury is a common pathophysiological stress state connected to various diseases, including acute glaucoma, retinal vascular obstruction, and diabetic retinopathy. Recent studies have suggested that geranylgeranylacetone (GGA) could increase heat shock protein70 (HSP70) level and reduce retinal ganglion cells (RGCs) apoptosis in a rat retinal I/R model. However, the underlying mechanism remains unclear. Moreover, the injury caused by retinal I/R includes not only apoptosis but also autophagy and gliosis, and the effects of GGA on autophagy and gliosis have not been reported. Our study established a retinal I/R model by anterior chamber perfusion pressuring to 110 mmHg for 60 min, followed by 4 h of reperfusion. The levels of HSP70, apoptosis-related proteins, GFAP, LC3-II, and PI3K/AKT/mTOR signaling proteins were determined by western blotting and qPCR after treatment with GGA, HSP70 inhibitor quercetin (Q), PI3K in-hibitor LY294002, and mTOR inhibitor rapamycin. Apoptosis was evaluated by TUNEL staining, meanwhile, HSP70 and LC3 were detected by immunofluorescence. Our results demonstrated that GGA-induced HSP70 expression significantly reduced gliosis, autophagosome accumulation, and apoptosis in retinal I/R injury, indicating that GGA exerted protective effects on retinal I/R injury. Moreover, the protective effects of GGA mechanistically relied on the activation of PI3K/AKT/mTOR signaling. In conclusion, GGA-induced HSP70 overexpression has protective effects on retinal I/R injury by activating PI3K/AKT/mTOR signaling."

基金机构："National Natural Science Foundation of China [31300911, 82171457]; Natural Science Foundation Project of CQ CSTS [CSTC2016jcyjA0073, CSTB2022NSCQ-MSX1083]"

基金资助正文："This study was funded by grants from the National Natural Science Foundation of China (NSFC No.31300911, 82171457) , the Natural Science Foundation Project of CQ CSTS (CSTC2016jcyjA0073, CSTB2022NSCQ-MSX1083) . We would like to thank the English editor of Editage ( www.editage.cn) ."