Autophagy induced by purple Emphasis Type="Italic

Authors: Cristiane C Denardin Leo A M Martins Mariana M Parisi Moema Queiroz Vieira Silvia R Terra Florencia M BarbéTuana Radovan Borojevic Márcia Vizzotto Tatiana Emanuelli Fátima Costa Rodrigues Guma

Publish Date: 2016/10/15

Volume: 33, Issue: 2, Pages: 197-206

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Abstract

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 organellemediated 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 wellestablished activated HSC line We evaluated the effects of 72h treatment with crescent concentrations of purple pitanga extract 5 to 100 μg/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 autophagyrelated 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 fibrosisThe authors acknowledge Conselho Nacional de Desenvolvimento Científico e Tecnológico CNPq Coordenação de Aperfeiçoamento de Pessoal de Nível Superior CAPES and Fundação de Amparo à Pesquisa do Rio Grande do Sul FAPERGS for financial support and Embrapa Clima Temperado for their collaboration and supply of fruit samples The authors thank to Centro de Microscopia e Microanálise CMMUFRGS by technical assistance in confocal and transmission electron microscopy

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