期刊
JOURNAL OF NUTRITIONAL BIOCHEMISTRY
卷 24, 期 5, 页码 903-911出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jnutbio.2012.06.008
关键词
CaMKK beta; Macroautophagy; mTOR; Pterostilbene; Vascular endothelial cell
资金
- National Natural Science Foundation of China [31101001]
- Science and Technology Developmental Project of Zhengzhou [20110942]
- Henan University of Technology [2011BS013, 2011BS017]
Chemical modulators of macroautophagy (herein referred to as autophagy) have aroused widespread interest among biologists and clinical physicians because of their potential for disease therapy. Pterostilbene (PT), a natural small-molecular compound, has been demonstrated to inhibit oxidized low-density lipoprotein (oxLDL)-induced apoptosis in vascular endothelial cells (VECs). The aim of the present study was to investigate whether and how PT could induce VEC autophagy. PT at 0.5 or 1 mu M could effectively induce autophagosome formation in human umbilical vein VECs (HUVECs). PT promoted autophagy via a rapid elevation in intracellular calcium ([Ca2+](i)) concentration and subsequent AMP-activated protein kinase alpha 1 subunit (AMPK alpha 1) activation, which in turn inhibited mammalian target of rapamycin, a potent inhibitor of autophagy. PT-induced AMPK alpha 1 activation and autophagy were refractory to the depletion of serine/threonine kinase 11 but depended on calcium/calmodulin-dependent protein kinase-beta activation. Interestingly, PT stimulated cytoprotective autophagy so as to aid in the removal of accumulated toxic oxLDL and inhibit apoptosis in HUVECs. Our study provides a potent small molecule enhancer of autophagy and a novel useful tool in exploring the molecular mechanisms for crosstalk between apoptosis and autophagy. PT could serve as a potential lead compound for developing a class of autophagy regulator as autophagy-related diseases therapy. (C) 2013 Elsevier Inc. All rights reserved.
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