标题：Distinct patterns of autophagy evoked by two benzoxazine derivatives in vascular endothelial cells
作者：Wang, Li; Dong, ZhiWu; Huang, Bin; Zhao, BaoXiang; Wang, Hua; Zhao, Jing; Kung, HsiangFu; Zhang, ShangLi; Miao, JunYing
作者机构：[Zhao, BaoXiang] Shandong Univ, Sch Chem & Chem Engn, Inst Organ Chem, Jinan 250100, Peoples R China.; [Wang, Li; Dong, ZhiWu; Huang, Bin; Zhao, Jin 更多
通讯作者地址：[Zhao, BX]Shandong Univ, Sch Chem & Chem Engn, Inst Organ Chem, Jinan 250100, Peoples R China.
关键词：autophagy; LC3; benzoxazine derivative; human umbilical vein endothelial; cell; annexin A7; calcium
摘要：Macroautophagy (referred to as autophagy) is an evolutionarily conserved, bulk-destruction process in eukaryotes. During this process, the cytoplasm containing long-lived proteins and organelles is engulfed into double-membrane autophagosomes, and ultimately undergoes enzymatic degradation within lysosomes. Autophagy serves as a prosurvival machinery, or it may contribute to cell death. Accumulating evidence indicates that autophagy is involved in the pathogenesis and intervention of various human diseases. Pharmacological autophagy modulators are arousing interest from biologists and clinical physicians in light of their potential for disease therapy and increasing our understanding of the mechanism of autophagy. In this study, we identified two autophagy enhancers, 6-amino-2,3-dihydro-3-hydroxymethyl-1,4-benzoxazine (ABO) and 6,8-dichloro-2,3-dihydro-3-hydroxymethyl-1,4-benzoxazine (DBO), in human umbilical vein endothelial cells (HUVECs) by autophagy assays, and demonstrate that ABO and DBO could stimulate autophagy in an mtor-independent and mtor-dependent manner, respectively; ABO-stimulated autophagy was attributed to the elevation of the Ca(2+) channel annexin A7 (ANXA7), whereas DBO's effect was due to the level of intracellular reactive oxygen species (ROS). Importantly, we found that ANXA7 was essential for autophagy induction via modulating the intracellular calcium concentration ([Ca(2+)](i)) in HUVECs. In summary, our work introduced two distinct autophagy enhancers and highlighted the critical role of ANXA7 in endothelial autophagy.