Fructose-1,6-bisphosphate reverts iron-induced phenotype of hepatic stellate cells by chelating ferrous ions

被引：6

作者：

Dias, Henrique Bregolin ^{[1
]}

Krause, Gabriele Catyana ^{[1
]}

Squizani, Eamin Daidr ^{[1
]}

Lima, Kelly Goulart ^{[1
]}

Schuster, Aline Daniele ^{[1
]}

Pedrazza, Leonardo ^{[1
]}

Basso, Bruno de Souza ^{[1
]}

Martha, Bianca Andrade ^{[1
]}

de Mesquita, Fernanda Cristina ^{[1
]}

Nunes, Fernanda Bordignon ^{[1
,2
]}

Fagundes Donadio, Marcio Vinicius ^{[1
]}

de Oliveira, Jarbas Rodrigues ^{[1
]}

机构：

[1] Pontificia Univ Catolica Rio Grande Sul PUCRS, Cellular Biophys & Inflammat Lab, Ave Ipiranga 6681,Predio 12,Bloco C,Sala 221, BR-90619900 Porto Alegre, RS, Brazil

[2] Univ Fed Ciencias Saude Porto Alegre, Basic Sci & Hlth Dept, Rua Sarmento Leite 245, BR-90050170 Porto Alegre, RS, Brazil

来源：

BIOMETALS | 2017年 / 30卷 / 04期

关键词：

Hepatic fibrosis; Fructose-1,6-bisphosphate; Hepatic stellate cell; Iron; ACTIVATED RECEPTOR-GAMMA; INDUCED APOPTOSIS; N-ACETYLCYSTEINE; RAT HEPATOCYTES; NITRIC-OXIDE; FIBROSIS; LIVER; GALACTOSAMINE; PROLIFERATION; FIBROGENESIS;

D O I：

10.1007/s10534-017-0025-y

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Hepatic fibrosis is an extracellular matrix deposition by hepatic stellate cells (HSC). Fibrosis can be caused by iron, which will lead to hydroxyl radical production and cell damage. Fructose-1,6-bisphosphate (FBP) has been shown to deliver therapeutic effects in many pathological situations. In this work, we aimed to test the effects of FBP in HSC cell line, GRX, exposed to an excess of iron (Fe). The Fe-treatment increased cell proliferation and FBP reversed this effect, which was not due to increased necrosis, apoptosis or changes in cell cycle. Oil Red-O staining showed that FBP successfully increased lipid content and lead GRX cells to present characteristics of quiescent HSC. Fe-treatment decreased PPAR-gamma expression and increased Col-1 expression. Both effects were reversed by FBP which also decreased TGF-beta 1 levels in comparison to both control and Fe groups. FBP, also, did not present scavenger activity in the DPPH assay. The treatment with FBP resulted in decreased proliferation rate, Col-1 expression and TGF-beta 1 release by HSC cells. Furthermore, activated PPAR-gamma and increased lipid droplets induce cells to become quiescent, which is a key event to reversion of hepatic fibrosis. FBP also chelates iron showing potential to improve Cell redox state.

引用

页码：549 / 558

页数：10

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