title: [Ophiopogonin D protects cardiomyocytes against doxorubicin-induced injury through suppressing endoplasmic reticulum stress].
abstract: This study aimed to examine whether ophiopogonin D (OP-D) is capable of protecting cardiomyocytes against DOX-induced injury and the mechanisms involved. H9c2 cells were cultured. MTT assay was used to evaluate cell viability and toxicity. Mito-tracker as fluorescence probe was used to measure ROS content raised from mitochondria. The mRNA and protein expression of ATF6alpha, GRP78 and CHOP were analyzed using real-time PCR and Western blotting, respectively. The results showed that a significant endoplasmic reticulum stress (ERS) was induced upon exposure of H9c2 cells to DOX as indicated by the increase in the expression of ERS related proteins, which was paralleled with the accumulation of reactive oxygen species (ROS) and decrease in the viability of H9c2 cells. Whereas, DOX-induced ROS accumulation and up-regulation of ERS related proteins were partially abolished by pretreatment with OP-D. Consequently, a DOX-induced ERS was mitigated by application of OP-D. Similarly, DOX-induced decrease in cell viability was partially attenuated by either inhibiting CHOP or pretreatment with N-acetylcysteine (NAC), an antioxidant. Moreover, cardiac ultrastructural abnormalities seen in mouse receiving DOX injections were obviously ameliorated by pretreatment of OP-D. Taken together, the present study proved that OP-D protects cardiomyocytes against DOX-induced injury, at least in part, through reducing ROS accumulation and alleviating ERS.
authors.forename: Chen
authors.initials: C
authors.lastname: Meng
authors.forename: Cai-Hua
authors.initials: CH
authors.lastname: Yuan
authors.forename: Chen-Chen
authors.initials: CC
authors.lastname: Zhang
authors.forename: Ming-Da
authors.initials: MD
authors.lastname: Wen
authors.forename: Yan-Hong
authors.initials: YH
authors.lastname: Gao
authors.forename: Xiao-Yu
authors.initials: XY
authors.lastname: Ding
authors.forename: Ying-Yu
authors.initials: YY
authors.lastname: Zhang
authors.forename: Zhao
authors.initials: Z
authors.lastname: Zhang
mesh_terms: D000111:Acetylcysteine; D051702:Activating Transcription Factor 6 / Q000378:metabolism; D000818:Animals; D000975:Antioxidants; D002460:Cell Line; D002470:Cell Survival; D004317:Doxorubicin / Q000009:adverse effects*; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D006360:Heat-Shock Proteins / Q000378:metabolism; D051379:Mice; D008928:Mitochondria / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000187:drug effects*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D012503:Saponins / Q000494:pharmacology*; D013150:Spirostans / Q000494:pharmacology*; D051742:Transcription Factor CHOP / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D051702:Activating Transcription Factor 6; D000975:Antioxidants; C497113:Atf6 protein, rat; C497251:Ddit3 protein, rat; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins; C000717248:Hspa5 protein, mouse; D017382:Reactive Oxygen Species; D012503:Saponins; D013150:Spirostans; D051742:Transcription Factor CHOP; C046996:ophiopogonin D; D004317:Doxorubicin; D000111:Acetylcysteine