USP49 inhibits ischemia–reperfusion‐induced cell viability suppression and apoptosis in human AC16 cardiomyocytes through DUSP1–JNK1/2 signaling
| Autor: | Qian Zhao, Hengbing Zhang, Wei Zhang, Yawei Xu, Zheng Liu, Yangyang Zhang |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
MAPK/ERK pathway Cell Survival MAP Kinase Signaling System Physiology p38 mitogen-activated protein kinases Clinical Biochemistry Apoptosis p38 Mitogen-Activated Protein Kinases Rats Sprague-Dawley 03 medical and health sciences 0302 clinical medicine Western blot medicine Animals Humans Mitogen-Activated Protein Kinase 8 Myocytes Cardiac Viability assay Protein kinase A medicine.diagnostic_test Chemistry Kinase JNK Mitogen-Activated Protein Kinases Dual Specificity Phosphatase 1 Cell Biology Cell biology 030104 developmental biology Reperfusion Injury 030220 oncology & carcinogenesis Mitogen-Activated Protein Kinases Signal transduction Ubiquitin Thiolesterase Signal Transduction |
| Zdroj: | Journal of Cellular Physiology. 234:6529-6538 |
| ISSN: | 1097-4652 0021-9541 |
| DOI: | 10.1002/jcp.27390 |
| Popis: | Dual-specificity protein phosphatases (DUSP) also known as mitogen-activated protein kinase (MAPK) phosphatases (MKPs) can dephosphorylate MAPKs, including extracellular signal-regulated kinase, c-Jun N-terminal kinase (JNK), and p38. DUSP1-mediated JNK dephosphorylation has been found to play an antiapoptotic role against cardiac ischemia-reperfusion (I/R) injury. However, the regulation of DUSP1-JNK pathway remains unclear. In the current study, ubiquitin-specific peptidase 49 (USP49) expression in human AC16 cardiomyocytes following I/R injury was measured by real-time polymerase chain reaction and western blot analysis. Cell viability, apoptosis, the Bax, Bcl-2, and DUSP1 expression, and the activity of MAPKs in AC16 cardiomyocytes following indicated treatment was measured by CCK-8, flow cytometry, and western blot analysis. The direct interaction between USP49 and DUSP1 was measured by coimmunoprecipitation and ubiquitination analysis. The effect of USP49 on apoptosis and JNK activity in rat cardiomyocytes following I/R injury was also measured by TUNEL and western blot analysis. Here, we found that USP49 expression was time-dependently increased in AC16 cardiomyocytes following I/R. I/R-induced cell apoptosis and JNK1/2 activation both in in vivo and in vitro reversed by USP49 overexpression in AC16 cardiomyocytes. Inhibiting JNK1/2 activation significantly inhibited USP49 knockdown-induced the cell viability inhibition, apoptosis and the JNK1/2 activation in AC16 cardiomyocytes. Moreover, USP49 positively regulated DUSP1 expression through deubiquitinating DUSP1. Overall, our findings establish USP49 as a novel regulator of DUSP1-JNK1/2 signaling pathway with a protective role in cardiac I/R injury. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text