期刊
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
卷 1853, 期 2, 页码 377-387出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbamcr.2014.10.030
关键词
Transient receptor potential canonical channel 4; Macroautophagy; Vascular endothelial cell; Trans-3,5,4'-trimethoxystilbene; Mammalian target of rapamycin
资金
- National Natural Science Foundation of China [31101001, 31100607, 31471296]
- Key Project of Henan Educational Committee [14A180028]
- Foundation for University Key Teacher by Henan Educational Committee [2013GGJS-078]
- Technological innovation incubator program from Henan University of Technology [11CXRC12]
- doctoral scientific research start-up foundation from Henan University of Technology [2011BS013]
Macroautophagy (autophagy) is an important factor affecting the function of vascular endothelial cells (VECs) and must be tightly regulated in these cells. However, the precise mechanisms underlying this process, particularly in the presence of serum, remain obscure. In this study, we identified trans-3,5,4'-trimethoxystilbene (TMS) as a potent small molecule inducer of autophagy in human umbilical vascular endothelial cells (HUVECs) in the presence of serum. Using high-throughput DNA microarray and siRNA transfection technologies, we demonstrated that TMS induced autophagy by up-regulating the expression of the transient receptor potential canonical channel 4 (TRPC4), an important cation channel in HUVECs. In addition, the overexpression of TRPC4 by plasmid transfection also induced autophagy. Mechanistic studies revealed that the up-regulation of TRPC4 increased the intracellular Ca2+ concentration, which, in turn, activated the Ca2+/CaMKK beta/AMPK pathway, leading to mTOR inhibition and autophagy. Our study identifies a novel role for TRPC4 in the regulation of autophagy in VECs. TMS is a useful new tool for investigating the molecular mechanism of autophagy in VECs and may serve as a potential lead compound for developing a class of autophagy inducers to treat autophagy-related diseases. (C) 2014 Elsevier B.V. All rights reserved.
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