title: Salidroside protects against hydrogen peroxide-induced injury in HUVECs via the regulation of REDD1 and mTOR activation.
abstract: Antioxidative therapy is considered an effective strategy for treating oxidative stress-induced apoptosis in cardiovascular diseases. Salidroside has been used as an antioxidative therapy for oxidative injury in cardiac diseases. However, the mechanism underlying its antioxidant effect is poorly understood. The present study aimed to investigate the pharmacological effects of salidroside on cultured human umbilical vein endothelial cells (HUVECs) under conditions of oxidative injury induced by hydrogen peroxide (H2O2) and the underlying mechanisms in vitro. HUVECs pretreated with or without salidroside for 24 h were exposed to H2O2-induced oxidative stress conditions for 6 h and then cell viability, apoptosis, HIF-1α, regulated in development and DNA damage responses-1 (REDD1) and the PI3K/Akt/mTOR pathway were investigated. The results demonstrated that salidroside effectively attenuated H2O2-impaired cell viability and the production of reactive oxygen species (ROS) in a concentration-dependent manner. Reduced H2O2-induced apoptosis and activation of the cellular PI3K/Akt/mTOR pathway were demonstrated in HUVECs pretreated with salidroside. Furthermore, the level of REDD1, a direct regulator of mitochondrial metabolism, significantly increased in parallel with the level of HIF-1α following pretreatment with salidroside. The antioxidative effect of salidroside was abrogated in REDD1 knockdown cells. However, LY294002, a PI3K inhibitor, attenuated the anti-apoptotic effect of salidroside and blocked the increase of Akt and mTOR; however, did not affect the antioxidative effect of salidroside. These findings suggested that salidroside was capable of protecting HUVECs against H2O2-induced apoptosis by activating the PI3K/Akt/mTOR-dependent pathway and inhibiting ROS production by activating REDD1.
authors: Department of Cardiology, Huashan Hospital of Fudan University, Shanghai 200040, PR China.
authors: Mao-Chun
authors: MC
authors: Xu
authors: Hai-Ming
authors: HM
authors: Shi
authors: Hao
authors: H
authors: Wang
authors: Xiu-Fang
authors: XF
authors: Gao
mesh_terms: D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D005960:Glucosides / Q000737:chemistry / Q000494:pharmacology*; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity*; D010636:Phenols / Q000737:chemistry / Q000494:pharmacology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D000975:Antioxidants; D005960:Glucosides; D006861:Hydrogen Peroxide; D010636:Phenols; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D017382:Reactive Oxygen Species; D058570:TOR Serine-Threonine Kinases; D014157:Transcription Factors; C469991:DDIT4 protein, human; C009172:rhodioloside