Vitamin E as a novel enhancer of macroautophagy in rat hepatocytes and H4-II-E cells
Vitamin E as a novel enhancer of macroautophagy in rat hepatocytes and H4-II-E cells
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DOI：
10.1016/j.bbrc.2010.03.103
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发表时间：
2010-04-16
影响因子：
3.1
通讯作者：
Kadowaki, Motoni
中科院分区：
文献类型：
--
作者：
Karim, Md. Razaul;Fujimura, Shinobu;Kadowaki, Motoni
自噬是由营养饥饿引起的细胞内大量降解过程，有助于细胞大分子的周转和细胞器的恢复活力。我们证明维生素E是一种新的营养增强剂，可促进新鲜分离的大鼠肝细胞和大鼠肝癌H4-II-E细胞的自噬。在存在或不存在氨基酸的情况下，以剂量依赖的方式向新鲜肝细胞补充维生素E(高达100mM)可显著增加蛋白质的分解。新建立的自噬通量指标--细胞质LC_3比率被维生素E显著增加，这有力地表明作用部位可能是自噬小体形成的早期步骤--LC_3转换步骤。典型的抗氧化剂α-硫辛酸抑制自噬，而H(2O)O(2)则刺激自噬。可以想象，自噬是由氧化应激刺激的，而这种刺激被细胞的抗氧化作用所抵消。然而，在我们的研究中，维生素E可能会增强H(2O)O(2)对自噬的过度刺激，而不是抑制它。从这些结果来看，维生素E通过一种新的细胞内LC_3比率，通过一种新的信号途径加速LC_3的转化，从而增加自噬，成为一种新的自噬增强剂。(C)2010 Elsevier Inc.保留所有权利。
Autophagy is an intracellular bulk degradation process induced by nutrient starvation, and contributes to macromolecular turnover and rejuvenation of cellular organelles. We demonstrated that vitamin E was a novel nutritional enhancer of autophagy in freshly isolated rat hepatocytes and rat hepatoma H4-II-E cells. Supplementation of fresh hepatocytes with vitamin E (up to 100 mu M) increased proteolysis significantly in the presence or absence of amino acids in a dose-dependent manner. The cytosolic LC3 ratio, a newly established index of autophagic flux, was significantly increased by vitamin E, strongly suggesting that the possible site of action is the LC3 conversion step, an early step in autophagosome formation. A typical antioxidant, alpha-lipoic acid, exerted autophagy suppression, while H(2)O(2) stimulated autophagy. It is conceivable that autophagy was stimulated by oxidative stress and this stimulation was cancelled by cellular antioxidative effects. However, in our studies, vitamin E could have enhanced autophagy over-stimulation by H(2)O(2), rather than suppress it. From these results, using a new cytosolic LC3 ratio, vitamin E increases autophagy by accelerating LC3 conversion through a new signaling pathway, emerging as a novel enhancer of autophagy. (C) 2010 Elsevier Inc. All rights reserved.