Distinct patterns of autophagy evoked by two benzoxazine derivatives in vascular endothelial cells.
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 (HUVEC s) 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 Ca2+ 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 ([Ca2+]i) in HUVEC s. In summary, our work introduced two distinct autophagy enhancers and highlighted the critical role of ANXA7 in endothelial autophagy.
Wang
Li
L
Institute of Developmental Biology, School of Life Science, Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital, China.
Dong
ZhiWu
Z
Huang
Bin
B
Zhao
BaoXiang
B
Wang
Hua
H
Zhao
Jing
J
Kung
HsiangFu
H
Zhang
ShangLi
S
Miao
JunYing
J
D017310:Annexin A7 / Q000378:metabolism; D001343:Autophagy / Q000187:drug effects*; D048588:Benzoxazines / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D042783:Endothelial Cells / Q000166:cytology* / Q000187:drug effects*; D006801:Humans; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D010078:Oxazines / Q000494:pharmacology*; D010588:Phagosomes / Q000187:drug effects / Q000378:metabolism; D020123:Sirolimus / Q000494:pharmacology; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D014471:Umbilical Veins / Q000166:cytology; D015854:Up-Regulation / Q000187:drug effects
C545140:6,8-dichloro-2,3-dihydro-3-hydroxymethyl-1,4-benzoxazine; C541593:6-amino-2,3-dihydro-3-hydroxymethyl-1,4-benzoxazine; D017310:Annexin A7; D048588:Benzoxazines; C477012:MAP1LC3A protein, human; D008869:Microtubule-Associated Proteins; D010078:Oxazines; D058570:TOR Serine-Threonine Kinases; D002118:Calcium; D020123:Sirolimus