title: Upregulation of peroxiredoxin III in doxorubicin-induced cytotoxicity and the FoxO3a-dependent expression in H9c2 cardiac cells.
abstract: Doxorubicin (DOX) is an efficient drug used in cancer therapy; however, it produces reactive oxygen species (ROS) that induce severe cytotoxicity, limiting its clinical application. The aim of the present study was to investigate the role of peroxiredoxin III (Prx III) in DOX-induced H9c2 cell injuries. Following DOX treatment, the expression of phosphorylated-FoxO3a (p-FoxO3a) was decreased and Prx III expression was increased in H9c2 cells. In order to detect whether oxidative stress was involved in the induction of Prx III expression by FoxO3a, exogenous H2O2was used to induce oxidative stress in the H9c2 cells. Apoptosis of H9c2 cardiomyocytes was assessed using methyl thiazolyl tetrazolium assay and Hoechst staining. The levels of Prx III and p-FoxO3a were evaluated using western blot analysis. As expected, H2O2was found to mimic the effect of DOX, decreasing the expression of p-FoxO3a and increasing the expression of Prx III. In addition, the study evaluated whether the transcription factor FoxO3a was essential for the expression of Prx III. Pretreatment of H9c2 cells with N-acetyl-L-cysteine (NAC), a scavenger of ROS, prior to exposure to DOX dramatically increased the phosphorylation of FoxO3a and led to a marked reduction in Prx III expression in the H9c2 cells. In conclusion, the results of the current study suggest that FoxO3a mediates the expression of Prx III in DOX-induced injuries.
authors.affiliation: Department of Clinical Laboratory, Affiliated Nanhua Hospital, University of South China, Hengyang, Hunan 421001, P.R. China.
authors.forename: Mi-Hua
authors.initials: MH
authors.lastname: Liu
authors.affiliation: Department of Pathology, Hunan Mawangdui Hospital, Changsha, Hunan 410016, P.R. China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Clinical Laboratory, Affiliated Nanhua Hospital, University of South China, Hengyang, Hunan 421001, P.R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: He
authors.affiliation: Department of Clinical Laboratory, Affiliated Nanhua Hospital, University of South China, Hengyang, Hunan 421001, P.R. China.
authors.forename: Tian-Ping
authors.initials: TP
authors.lastname: Tan
authors.affiliation: Department of Clinical Laboratory, Affiliated Nanhua Hospital, University of South China, Hengyang, Hunan 421001, P.R. China.
authors.forename: Shao-Jian
authors.initials: SJ
authors.lastname: Wu
authors.affiliation: Department of Clinical Laboratory, Affiliated Nanhua Hospital, University of South China, Hengyang, Hunan 421001, P.R. China.
authors.forename: Hong-Yun
authors.initials: HY
authors.lastname: Fu
authors.affiliation: Department of Clinical Laboratory, Affiliated Nanhua Hospital, University of South China, Hengyang, Hunan 421001, P.R. China.
authors.forename: Yu-Dan
authors.initials: YD
authors.lastname: Chen
authors.affiliation: Department of Clinical Laboratory, Affiliated Nanhua Hospital, University of South China, Hengyang, Hunan 421001, P.R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Clinical Laboratory, Affiliated Nanhua Hospital, University of South China, Hengyang, Hunan 421001, P.R. China.
authors.forename: Qun-Fang
authors.initials: QF
authors.lastname: LE
authors.affiliation: Department of Cardiology/Cardiac Catheterisation Lab, Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, P.R. China.
authors.forename: Heng-Jing
authors.initials: HJ
authors.lastname: Hu
authors.affiliation: Department of Cardiology, The First Hospital of Changsha, Changsha, Hunan 410005, P.R. China.
authors.forename: Cong
authors.initials: C
authors.lastname: Yuan
authors.affiliation: Department of Pathology, The Third People's Hospital of Huizhou, Guangzhou Medical University, Huizhou, Guangdong 516002, P.R. China.
authors.forename: Xiao-Long
authors.initials: XL
authors.lastname: Lin
keywords: FoxO3a; cardiomyocytes; doxorubicin; peroxiredoxin III