Autophagy induced by purple pitanga (Eugenia uniflora L.) extract triggered a cooperative effect on inducing the hepatic stellate cell death
Autophagy induced by purple pitanga (Eugenia uniflora L.) extract triggered a cooperative effect on inducing the hepatic stellate cell death
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DOI：
10.1007/s10565-016-9366-5
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发表时间：
2017-04-01
影响因子：
6.1
通讯作者：
Costa Rodrigues Guma, Fatima
中科院分区：
文献类型：
--
作者：
Denardin, Cristiane C.;Martins, Leo A. M.;Costa Rodrigues Guma, Fatima
活化的肝星状细胞（HSC）是肝纤维化中I型胶原的主要来源。独花丁香是一种广泛分布于南美洲的树种。E.独花属水果--通常称为皮唐卡--已经显示出有益的特性。自噬有助于维持细胞内环境的稳定和在应激条件下的存活，但它也被认为是一种替代性的细胞死亡途径。线粒体在细胞死亡信号中起着关键作用。受损线粒体的自噬是细胞抵抗细胞器介导的细胞死亡信号传导的重要细胞防御机制。我们以前发现，紫皮坦加提取物诱导线粒体功能障碍，细胞周期停滞，并在GRX细胞，一个完善的活化HSC系凋亡和坏死死亡。我们评估了用新月形浓度的紫皮坦加提取物（5至100 μ g/mL）处理72小时对触发GRX细胞中的自噬的影响，因为这是细胞毒性条件下的细胞的重要机制。我们发现，所有处理过的细胞呈现自噬相关蛋白7（ATG 7）的mRNA表达增加。同时，流式细胞术和超微结构分析处理的细胞显示增加的自噬体/autolysosomes，从而导致增加的线粒体自噬。由于紫皮坦加提取物先前被发现对GRX细胞具有广泛的细胞毒性，我们假设自噬有助于这种情况，其中细胞死亡似乎是不可避免的命运。因此，紫皮坦加提取物诱导活化HSC死亡的有效性可以作为治疗肝纤维化的良好候选药物。
Activated hepatic stellate cells (HSC) are the major source of collagen I in liver fibrosis. Eugenia uniflora L. is a tree species that is widely distributed in South America. E. uniflora L. fruit-popularly known as pitanga-has been shown to exert beneficial properties. Autophagy contributes to the maintenance of cellular homeostasis and survival under stress situation, but it has also been suggested to be an alternative cell death pathway. Mitochondria play a pivotal role on signaling cell death. Mitophagy of damaged mitochondria is an important cell defense mechanism against organelle-mediated cell death signaling. We previously found that purple pitanga extract induced mitochondrial dysfunction, cell cycle arrest, and death by apoptosis and necrosis in GRX cells, a well-established activated HSC line. We evaluated the effects of 72-h treatment with crescent concentrations of purple pitanga extract (5 to 100 mu g/mL) on triggering autophagy in GRX cells, as this is an important mechanism to cells under cytotoxic conditions. We found that all treated cells presented an increase in the mRNA expression of autophagy-related protein 7 (ATG7). Concomitantly, flow cytometry and ultrastructural analysis of treated cells revealed an increase of autophagosomes/autolysosomes that consequentially led to an increased mitophagy. As purple pitanga extract was previously found to be broadly cytotoxic to GRX cells, we postulated that autophagy contributes to this scenario, where cell death seems to be an inevitable fate. Altogether, the effectiveness on inducing activated HSC death can make purple pitanga extract a good candidate on treating liver fibrosis.