| First Author | Yao Y | Year | 2017 |
| Journal | Biochem Biophys Res Commun | Volume | 493 |
| Issue | 3 | Pages | 1288-1295 |
| PubMed ID | 28965952 | Mgi Jnum | J:253898 |
| Mgi Id | MGI:6103291 | Doi | 10.1016/j.bbrc.2017.09.153 |
| Citation | Yao Y, et al. (2017) Interleukin-33 attenuates doxorubicin-induced cardiomyocyte apoptosis through suppression of ASK1/JNK signaling pathway. Biochem Biophys Res Commun 493(3):1288-1295 |
| abstractText | Interleukin-33 (IL-33), a new member of the IL-1 cytokine family, has cardiac protective effect in many circumstances. The aims of present study are to assess whether IL-33 can protect cardiomyocytes from doxorubicin (DOX)-induced apoptosis and the mechanism involved in the protection. Cardiomyocytes derived from either wild-type or c-Jun N-terminal kinase deficient (JNK(-/-)) mice were challenged with DOX (1 muM) with or without IL-33 (10 ng/ml). Myocyte apoptosis was assessed by measuring Caspase 3 activity, fragmented DNA and the TUNEL staining. In addition, cardiomyocyte reactive oxygen species (ROS) was assessed by measuring 2'',7''-dichlorofluorescin diacetate (DCFDA); apoptosis signal-regulating kinase 1(ASK1) and JNK phosphorylation were assessed with western blot analysis. Treatment of cardiomyocyes with DOX resulted in ROS generation, ASK1 and JNK phosphorylation and myocyte apoptosis. IL-33 inhibited the DOX-induced ROS, prevented ASK1 and JNK phosphorylation and attenuated the DOX-induced myocyte apoptosis. Genetic inhibition of ASK1 (ASK1 siRNA transfection) and JNK (JNK(-/-)) ameliorated the cardiac-protective effect of IL-33. Moreover, inhibition of ASK1 prevented the DOX-induced phosphorylation of JNK, while inhibition of JNK showed no effect on DOX-induced ASK1 phosphorylation. Our study indicates that: 1) ASK1/JNK signaling pathway is involved in DOX-induced cardiomyocyte apoptosis; 2) IL-33 protects cardiomyocytes from DOX-induced myocyte apoptosis through inhibition of the ASK1/JNK signaling pathway. IL-33 may have therapeutic potential for DOX-induced cardiac injury. |
