کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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1990056 | 1540673 | 2013 | 9 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Pterostilbene, a natural small-molecular compound, promotes cytoprotective macroautophagy in vascular endothelial cells Pterostilbene, a natural small-molecular compound, promotes cytoprotective macroautophagy in vascular endothelial cells](/preview/png/1990056.png)
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 μM 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 α1 subunit (AMPKα1) activation, which in turn inhibited mammalian target of rapamycin, a potent inhibitor of autophagy. PT-induced AMPKα1 activation and autophagy were refractory to the depletion of serine/threonine kinase 11 but depended on calcium/calmodulin-dependent protein kinase kinase-β 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.
Journal: The Journal of Nutritional Biochemistry - Volume 24, Issue 5, May 2013, Pages 903–911