The PERK/Nrf2 pathway mediates endoplasmic reticulum stress-induced injury by upregulating endoplasmic reticulophagy in H9c2 cardiomyoblasts
| Autor: | Huimin Mao, Xiu-Hua Liu, You Wang, Tianqi Tao, Xiao-Reng Wang, Jianli Wang |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Thapsigargin NF-E2-Related Factor 2 Reticulophagy Apoptosis Endoplasmic Reticulum environment and public health 030226 pharmacology & pharmacy General Biochemistry Genetics and Molecular Biology eIF-2 Kinase 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Downregulation and upregulation Animals Myocytes Cardiac Phosphorylation General Pharmacology Toxicology and Pharmaceutics Protein kinase A Cells Cultured biology Kinase Endoplasmic reticulum General Medicine Tunicamycin Endoplasmic Reticulum Stress Activating Transcription Factor 4 Rats Cell biology Oxidative Stress 030104 developmental biology chemistry biology.protein Beclin-1 Microtubule-Associated Proteins Calreticulin Signal Transduction |
| Zdroj: | Life Sciences. 237:116944 |
| ISSN: | 0024-3205 |
| DOI: | 10.1016/j.lfs.2019.116944 |
| Popis: | Aims Endoplasmic reticulum stress (ERS) is an evolutionarily conserved cell stress response. Recently, it was found that ERS induces not only apoptosis but also endoplasmic reticulophagy (ER-phagy). A previous study demonstrated that inhibition of ER-phagy alleviates cell injury. The purpose of this study was to investigate the involvement of the protein kinase R-like ER kinase (PERK)/nuclear factor erythroid 2-related factor 2 (Nrf2) pathway in ERS-induced ER-phagy in H9c2 cardiomyoblasts. To address this aim, cells were treated with ERS inhibitors and a Nrf2 inhibitor before establishment of thapsigargin (TG)- or tunicamycin (TM)-induced ERS models in H9c2 cardiomyoblasts. Main methods Transmission electron microscopy and immunofluorescence staining were used to detect ER-phagy. Western blotting was employed to detect the levels of calreticulin (CRT), total and phosphorylated PERK, nuclear Nrf2, activated transcription factor 4 (ATF4), light chain 3B (LC3B)-II and Beclin 1. Immunofluorescence staining was used to assess subcellular location of Nrf2. Key finding TG or TM induced H9c2 cell injury and ER-phagy and upregulated CRT expression, PERK phosphorylation, Nrf2 nuclear translocation, and expression of ATF4, Beclin 1, and LC3B-II compared with control cells. Treatment with ERS inhibitors decreased TG- or TM-induced ER-phagy, downregulated CRT expression, PERK phosphorylation, Nrf2 nuclear translocation and the expression of ATF4, Beclin 1 and LC3B-II. Moreover, a Nrf2 inhibitor downregulated the expression of ATF4, Beclin 1 and LC3B-II and alleviated TG- or TM-induced ER-phagy and H9c2 cell injury. Significance These findings suggest that the PERK/Nrf2 pathway mediates upregulation of ER-phagy, thereby inducing cell injury in H9c2 cardiomyoblasts. |
| Databáze: | OpenAIRE |
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