Salubrinal Alleviates Pressure Overload-Induced Cardiac Hypertrophy by Inhibiting Endoplasmic Reticulum Stress Pathway.
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.
School of Life Sciences, Gwangju Institute of Science and Technology (GIST), Gwangju 61005, Korea.
Shilpa
S
Rani
School of Life Sciences, Gwangju Institute of Science and Technology (GIST), Gwangju 61005, Korea.
Pradeep Kumar
PK
Sreenivasaiah
School of Life Sciences, Gwangju Institute of Science and Technology (GIST), Gwangju 61005, Korea.
Chunghee
C
Cho
School of Life Sciences, Gwangju Institute of Science and Technology (GIST), Gwangju 61005, Korea.
Do Han
DH
Kim
D000818:Animals; D006332:Cardiomegaly / Q000188:drug therapy* / Q000503:physiopathology; D002934:Cinnamates / Q000494:pharmacology*; D004195:Disease Models, Animal; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D051381:Rats; D013890:Thiourea / Q000031:analogs & derivatives* / Q000494:pharmacology
D002934:Cinnamates; C496827:salubrinal; D013890:Thiourea
ER stress; GRP; TGF-β; eIF2α; transverse aortic constriction