title: Rosmarinic Acid suppressed high glucose-induced apoptosis in H9c2 cells by ameliorating the mitochondrial function and activating STAT3.
abstract: Mitochondrial injury characterized by intracellular reactive oxygen species (ROS) accumulation plays a critical role in hyperglycemia-induced myocardium dysfunction. Previous studies have demonstrated that Rosmarinic Acid (RA) treatment and activating Signal transducer and activator of transcription 3 (STAT3) signaling pathway have protective effects on mitochondrial dysfunction in cardiomyocyte, but there is little data regarding cardiomyocyte under condition of high-glucose. The present study was undertaken to determine the relationship between RA and STAT3 activation, as well as their effects on high glucose-induced mitochondrial injury and apoptosis in H9c2 cardiomyocyte. Our results revealed that RA pretreatment suppressed high glucose-induced apoptosis in H9c2 cells. Moreover, the effect of RA on apoptosis was related with improved mitochondrial function, which was demonstrated by that RA attenuated high glucose-induced ROS generation, inhibited mitochondrial permeability transition pore (MPTP) activation, suppressed cytochrome c release and caspase-3 activation. In addition, the phosphorylation of STAT3 in H9c2 cells was inhibited under condition of high-glucose, but RA improved STAT3 phosphorylation. Importantly, inhibition of STAT3 expression by using STAT3-siRNA partly suppressed the effect of RA on high glucose-induced apoptosis. Taken together, pretreatment with RA suppressed high glucose-induced apoptosis in cardiomyocyte by ameliorating mitochondrial function and activating STAT3.
authors.affiliation: Department of Cardiology, The Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710004, China.
authors.forename: Jiayu
authors.initials: J
authors.lastname: Diao
authors.affiliation: Department of Cardiology, The Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710004, China. Electronic address: docweijin@163.com.
authors.forename: Jin
authors.initials: J
authors.lastname: Wei
authors.affiliation: Department of Cardiology, The Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710004, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Yan
authors.affiliation: Department of Cardiology, The Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710004, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Cardiology, The Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710004, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Cardiology, The Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710004, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Lin
authors.affiliation: Key Laboratory of Trace Elements and Endemic Disease of Ministry of Health, Xi'an Jiaotong University School of Medicine, Shaanxi 710061, China.
authors.forename: Yanhe
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Cardiology, The Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710004, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Li
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002460:Cell Line; D002934:Cinnamates / Q000008:administration & dosage*; D053630:Depsides / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005947:Glucose / Q000008:administration & dosage*; D006801:Humans; D008929:Mitochondria, Heart / Q000187:drug effects / Q000502:physiology*; D032342:Muscle Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D000097123:Rosmarinic Acid
chemical_list: D002934:Cinnamates; D053630:Depsides; D005947:Glucose; D050796:STAT3 Transcription Factor; D000097123:Rosmarinic Acid; C494086:STAT3 protein, human
keywords: Apoptosis; Cardiomyocyte; High-glucose; Mitochondrial injury; Rosmarinic Acid; STAT3