title: Autophagy induced by purple pitanga (Eugenia uniflora L.) extract triggered a cooperative effect on inducing the hepatic stellate cell death.
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 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 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 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.
authors.affiliation: Programa de Pós-Graduação em Ciências Biológicas-Bioquímica, ICBS, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brasil.|Curso de Farmácia, Universidade Federal do Pampa (UNIPAMPA), Campus Uruguaiana, Uruguaiana, RS, Brasil.
authors.forename: Cristiane C
authors.initials: CC
authors.lastname: Denardin
authors.affiliation: Programa de Pós-Graduação em Ciências Biológicas-Bioquímica, ICBS, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brasil.
authors.forename: Leo A M
authors.initials: LA
authors.lastname: Martins
authors.affiliation: Programa de Pós-Graduação em Ciências Biológicas-Bioquímica, ICBS, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brasil.
authors.forename: Mariana M
authors.initials: MM
authors.lastname: Parisi
authors.affiliation: Programa de Pós-Graduação em Ciências Biológicas-Bioquímica, ICBS, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brasil.
authors.forename: Moema Queiroz
authors.initials: MQ
authors.lastname: Vieira
authors.affiliation: Programa de Pós-Graduação em Ciências Biológicas-Bioquímica, ICBS, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brasil.
authors.forename: Silvia R
authors.initials: SR
authors.lastname: Terra
authors.affiliation: Programa de Pós-Graduação em Ciências Biológicas-Bioquímica, ICBS, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brasil.
authors.forename: Florencia M
authors.initials: FM
authors.lastname: Barbé-Tuana
authors.affiliation: Departamento de Histologia e Embriologia, ICB, UFRJ, Rio de Janeiro, RJ, Brasil.
authors.forename: Radovan
authors.initials: R
authors.lastname: Borojevic
authors.affiliation: Empresa Brasileira de Pesquisa Agropecuária de Clima Temperado, Pelotas, RS, Brasil.
authors.forename: Márcia
authors.initials: M
authors.lastname: Vizzotto
authors.affiliation: Núcleo Integrado de Desenvolvimento em Análises Laboratoriais (NIDAL), Departamento de Tecnologia e Ciência de Alimentos, Universidade Federal de Santa Maria, Santa Maria, RS, Brasil.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Emanuelli
authors.affiliation: Programa de Pós-Graduação em Ciências Biológicas-Bioquímica, ICBS, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brasil. fatima.guma@ufrgs.br.|Departamento de Bioquímica, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos 2600-Anexo, Lab 21, CEP: 90035-003, Porto Alegre, RS, Brasil. fatima.guma@ufrgs.br.|Centro de Microscopia e Microanálise, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brasil. fatima.guma@ufrgs.br.
authors.forename: Fátima Costa Rodrigues
authors.initials: FC
authors.lastname: Guma
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D000071182:Autophagosomes / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D001343:Autophagy / Q000187:drug effects*; D002460:Cell Line; D000068856:Eugenia / Q000737:chemistry*; D055166:Hepatic Stellate Cells / Q000187:drug effects / Q000473:pathology*; D008103:Liver Cirrhosis / Q000188:drug therapy / Q000473:pathology; D008247:Lysosomes / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D010936:Plant Extracts
keywords: Autophagy; Cell death; Eugenia uniflora L. fruits; Hepatic stellate cells; Liver fibrosis