Proanthocyanidin protects H9C2 cells against hypoxia/reoxygenation injury via JAK2/STAT3 signaling pathway.
- Author:
Chen-Bin YU
1
;
Guo-Long ZHAO
2
;
Li-Ming YU
2
;
Shi-Qiang YU
2
;
Wei-Xun DUAN
3
;
Hai-Feng ZHANG
4
Author Information
1. Emergency Department of Jiangsu Research Institute of Traditional Chinese Medicine, Nanjing 210028, China.
2. Department of Cardiovascular Surgery, Xijing Hospital, The Fourth Military Medical University, Xi'an 710032, China.
3. Department of Cardiovascular Surgery, Xijing Hospital, The Fourth Military Medical University, Xi'an 710032, China. duanweixun@126.com.
4. Experimental Teaching Center, The Fourth Military Medical University, Xi'an 710032, China. hfzhang@fmmu.edu.cn.
- Publication Type:Journal Article
- MeSH:
Animals;
Apoptosis;
Cell Hypoxia;
Cell Line;
Cell Survival;
Endoplasmic Reticulum Stress;
In Situ Nick-End Labeling;
Janus Kinase 3;
Oxidation-Reduction;
Phosphorylation;
Proanthocyanidins;
Protective Agents;
RNA, Small Interfering;
Rats;
STAT3 Transcription Factor;
Signal Transduction;
Up-Regulation
- From:
Acta Physiologica Sinica
2016;68(5):568-574
- CountryChina
- Language:Chinese
-
Abstract:
The present study was aimed to investigate the underlying mechanisms of the protective effect of proanthocyanidin (Pro) against hypoxia/reoxygenation (H/R) injury in H9C2 cells with a focus on Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway. H9C2 cells were randomly assigned to 5 groups, including the control group (Con), the H/R-injured group (H/R), the Pro-treated group (H/R+Pro), the JAK2 siRNA-treated group (H/R+Pro+JAK2 siRNA) and the JAK2 siRNA control group (H/R+JAK2 siRNA). The cells were pretreated with Pro (40 µmol/L) for 8 h before 2 h of hypoxia and 4 h of reoxygenation. Cellular viability and apoptosis rate were detected by MTT and TUNEL methods, and superoxide generation was measured. JAK2/STAT3 signaling, oxidative stress markers and endoplasmic reticulum stress markers were also detected by Western blot. We found that Pro treatment significantly improved cellular viability and reduced apoptosis rate in H/R-treated H9C2 cells. In addition, Pro treatment significantly up-regulated the phosphorylation levels of JAK2 and STAT3, down-regulated the superoxide generation, gp91, glucose-regulated protein 78 (GRP78), CCAAT/enhancer binding protein homologous protein (CHOP) and caspase-12 expression. However, these protective effects of Pro were all attenuated by JAK2 siRNA administration. Taken together, we demonstrated that Pro protects H9C2 cells against H/R-induced oxidative stress and endoplasmic reticulum stress injury via JAK2/STAT3 signaling pathway.
