Blocking PERK resuces vascular smooth muscle cells from homocysteine-induced ER stress and apoptosis.
Front Biosci (Landmark Ed)
; 25(3): 536-548, 2020 01 01.
Article
en En
| MEDLINE
| ID: mdl-31585902
ABSTRACT
Hyperhomocysteinemia induces stress response in endoplasmic reticulum (ERS). Here, we tested whether blockage of homocysteine (Hcy) induced ERS and subsequent apoptosis in vascular smooth muscle cells can be inhibited by blockage of PERK/eIF2α/ATF4/CHOP signaling. Short-term exposure of vascular smooth muscle cells to Hcy led to the phosphorylation of PERK (pPERK), which in turn, phosphorylated eIF2 alpha (peIF2a) and inhibited the unfolded protein response. Long-term Hcy exposure, however, increased the expression of ATF-4 and CHOP and led to apoptosis. Treatment of cells with salubrinal, a specific inhibitor for eIF2a decreased the expression of ATF-4 and CHOP, and prevented apoptosis. Together, the results show that PERK pathway is involved in Hcy-induced vascular smooth muscle cell apoptosis and that blocking the PERK pathway protects against this injury.
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Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Transducción de Señal
/
Apoptosis
/
EIF-2 Quinasa
/
Miocitos del Músculo Liso
/
Estrés del Retículo Endoplásmico
/
Homocisteína
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Front Biosci (Landmark Ed)
Año:
2020
Tipo del documento:
Article
País de afiliación:
China