Protective role of calreticulin in HFE hemochromatosis.
Protective role of calreticulin in HFE hemochromatosis.
复制标题
钙网蛋白在 HFE 血色素沉着症中的保护作用。
DOI：
10.1016/j.freeradbiomed.2007.09.014
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发表时间：
2008
影响因子：
7.4
通讯作者：
deSousa,Maria
中科院分区：
文献类型：
--
作者：
Pinto,JorgeP;Ramos,Pedro;deAlmeida,SérgioF;Oliveira,Susana;Breda,Laura;Michalak,Marek;Porto,Graça;Rivella,Stefano;deSousa,Maria
HFE gene mutations are associated with over 80% of cases of hereditary hemochromatosis (HH), an iron-overload disease in which the liver is the most frequently affected organ. Research on HFE has traditionally focused on its interaction with the transferrin receptor. More recent studies have suggested a more complex function for this nonclassical MHC-I protein. The aim of this study was to examine how HFE and its two most common mutations affect the expression of selected genes in a hepatocyte-like cell line. Gene expression was analyzed in HepG2 cells overexpressing wild-type and mutant HFE. The effect of HFE in iron import and oxidative stress levels was assessed. Unfolded protein response (UPR)-activated gene expression was analyzed in peripheral blood mononuclear cells from characterized HH patients. C282Y HFE down-regulated hepcidin and enhanced calreticulin mRNA expression. Calreticulin levels correlated with intracellular iron increase and were associated with protection from oxidative stress. In C282Y+/+patients calreticulin levels correlated with the expression of the UPR marker BiP and showed a negative association with the number of hereditary hemochromatosis clinical manifestations. The data show that expression of C282Y HFE triggers a stress-protective response in HepG2 cells and suggest a role for calreticulin as a modifier of the clinical expression of HH.
