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α-Asarone Blocks 7β-hydroxycholesterol-exposed Macrophage Injury Through Blocking elF2α Phosphorylation and Prompting beclin-1-dependent Autophagy

α-Asarone Blocks 7β-hydroxycholesterol-exposed Macrophage Injury Through Blocking elF2α Phosphorylation and Prompting beclin-1-dependent Autophagy

Sin-Hye Park, Min-Kyung Kang, Yean-Jung Choi, Yun-Ho Kim, Lucia Dwi Antika, Dong Yeon Kim, Eun-Jung Lee, Soon Sung Lim, Young-Hee Kang

Oncotarget. 2017 Jan 31;8(5):7370-7383.

PMID: 28088783

Abstract:

Macrophage apoptosis is salient in advanced atherosclerotic lesions and is induced by several stimuli including endoplasmic reticulum (ER) stress. This study examined that α-asarone present in purple perilla abrogated macrophage injury caused by oxysterols via ER stress- and autophagy-mediated mechanisms. Nontoxic α-asarone at 1-20 μM attenuated 7β-hydroxycholesterol-induced activation of eukaryotic initiation factor 2α in macrophages leading to C/EBP homologous protein (CHOP) expression and apoptosis due to sustained ER stress. The α-asarone treatment increased the formation of autophagolysosomes localizing in perinuclear regions of 7β-hydroxycholesterol-exposed macrophages. Consistently, this compound promoted the induction of the key autophagic proteins of beclin-1, vacuolar protein sorting 34 and p150 responsible for vesicle nucleation, and prompted the conversion of microtubule-associated protein 1A/1B-light chain 3 and the induction of p62, neighbor of BRCA1 and autophagy-related (Atg) 12-Atg5-Atg16L conjugate involved in phagophore expansion and autophagosome formation. Additionally, α-asarone increased ER phosphorylation of bcl-2 facilitating beclin-1 entry to autophagic process. Furthermore, the deletion of Atg5 or beclin-1 gene enhanced apoptotic CHOP induction. Collectively, α-asarone-stimulated autophagy may be potential multi-targeted therapeutic avenues in treating ER stress-associated macrophage apoptosis.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP566278	7β-Hydroxycholesterol		566-27-8	Price

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