XXXX ameliorates endoplasmic reticulum stress in endothelial cells after @entity519 /reoxygenation via M3 AChR-AMPK signaling.

@entity129 @entity10730 @entity8580 @entity1885 @entity4139 @entity63 @entity1977 @entity519 @entity8582 @entity3451 @entity413 @entity65 @entity130 @entity934
UNASSIGNED: Endoplasmic reticulum (ER) stress is associated with various @entity65 . However, its pathophysiological relevance and the underlying mechanisms in the context of @entity519 /reoxygenation (H/R) in endothelial cells are not fully understood. Previous findings have suggested that @entity934 ( @entity3451 ), the major @entity129 , protected against @entity130 by activating @entity8582 -activated protein kinase (AMPK). This study investigated the role of ER stress in endothelial cells during H/R and explored the beneficial effects of @entity3451 . Our results showed that H/R triggered ER stress and apoptosis in endothelial cells, evidenced by the elevation of @entity413 -regulated protein 78, cleaved caspase-12 and C/EBP homologous protein expression. @entity3451 significantly decreased ER stress and @entity10730 mediated @entity1977 - @entity1885 nick end labeling positive cells and restored ER ultrastructural changes induced by H/R, possibly via protein kinase-like ER kinase and @entity8580 -requiring kinase 1 pathways. Additionally, @entity4139 , a type-3 muscarinic @entity3451 receptor (M3 AChR) inhibitor, abolished @entity3451 -mediated increase in AMPK phosphorylation during H/R. Furthermore, M3 AChR or AMPK siRNA abrogated the @entity3451 -elicited the attenuation of ER stress in endothelial cells, indicating that the salutary effects of @entity3451 were likely mediated by M3 AChR-AMPK signaling. Overall, @entity3451 activated AMPK through M3 AChR, thereby inhibited H/R-induced ER stress and apoptosis in endothelial cells. We have suggested for the first time that AMPK may function as an essential intermediate step between M3 AChR stimulation and inhibition of ER stress-associated apoptotic pathway during H/R, which may help to develop novel therapeutic approaches targeting ER stress to prevent or alleviate @entity63 /reperfusion injury.
