Salubrinal Alleviates Pressure Overload-Induced Cardiac Hypertrophy by Inhibiting Endoplasmic Reticulum Stress Pathway
| Autor: | Shilpa Rani, Pradeep Kumar Sreenivasaiah, Do Han Kim, Chunghee Cho |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
TGF-β
Male 0301 basic medicine eIF2α Cardiomegaly Pharmacology Article Muscle hypertrophy Salubrinal Mice 03 medical and health sciences chemistry.chemical_compound transverse aortic constriction Animals Medicine Molecular Biology Pressure overload business.industry Endoplasmic reticulum Thiourea Protein phosphatase 1 Cell Biology General Medicine Endoplasmic Reticulum Stress Endothelin 1 Rats Mice Inbred C57BL Disease Models Animal 030104 developmental biology chemistry Cinnamates cardiovascular system Unfolded protein response GRP Myocardial fibrosis ER stress business |
| Zdroj: | Molecules and Cells |
| ISSN: | 0219-1032 1016-8478 |
| Popis: | Pathological hypertrophy of the heart is closely associated with endoplasmic reticulum stress (ERS), leading to maladaptations such as myocardial fibrosis, induction of apoptosis, and cardiac dysfunctions. Salubrinal is a known selective inhibitor of protein phosphatase 1 (PP1) complex involving dephosphorylation of phospho-eukaryotic translation initiation factor 2 subunit (p-eIF2)-α, the key signaling process in the ERS pathway. In this study, the effects of salubrinal were examined on cardiac hypertrophy using the mouse model of transverse aortic constriction (TAC) and cell model of neonatal rat ventricular myocytes (NRVMs). Treatment of TAC-induced mice with salubrinal (0.5 mg·kg−1·day−1) alleviated cardiac hypertrophy and tissue fibrosis. Salubrinal also alleviated hypertrophic growth in endothelin 1 (ET1)-treated NRVMs. Therefore, the present results suggest that salubrinal may be a potentially efficacious drug for treating pathological cardiac remodeling. |
| Databáze: | OpenAIRE |
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