Hereditary hemochromatosis: An opportunity for gene therapy

Levels of body iron should be tightly controlled to prevent the formation of oxygen radicals, lipoperoxidation, genotoxicity, and the production of cytotoxic cytokines, which result in damage to a number of organs. Enterocytes in the intestinal villae are involved in the apical uptake of iron from t...

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Autores principales:	EZQUER,FERNANDO, NÚÑEZ,MARCO T, ROJAS,ALEJANDRO, ASENJO,JUAN, ISRAEL,YEDY
Lenguaje:	English
Publicado:	Sociedad de Biología de Chile 2006
Materias:	iron intestine hemochromatosis gene therapy HFE DMT1 cirrhosis
Acceso en línea:	http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602006000100014
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spelling	oai:scielo:S0716-976020060001000142006-06-30Hereditary hemochromatosis: An opportunity for gene therapyEZQUER,FERNANDONÚÑEZ,MARCO TROJAS,ALEJANDROASENJO,JUANISRAEL,YEDY iron intestine hemochromatosis gene therapy HFE DMT1 cirrhosis Levels of body iron should be tightly controlled to prevent the formation of oxygen radicals, lipoperoxidation, genotoxicity, and the production of cytotoxic cytokines, which result in damage to a number of organs. Enterocytes in the intestinal villae are involved in the apical uptake of iron from the intestinal lumen; iron is further exported from the cells into the circulation. The apical divalent metal transporter-1 (DMT1) transports ferrous iron from the lumen into the cells, while the basolateral transporter ferroportin extrudes iron from the enterocytes into the circulation. Patients with hereditary hemochromatosis display an accelerated transepithelial uptake of iron, which leads to body iron accumulation that results in cirrhosis, hepatocellular carcinoma, pancreatitis, and cardiomyopathy. Hereditary hemochromatosis, a recessive genetic condition, is the most prevalent genetic disease in Caucasians, with a prevalence of one in 300 subjects. The majority of patients with hereditary hemochromatosis display mutations in the gene coding for HFE, a protein that normally acts as an inhibitor of transepithelial iron transport. We discuss the different control points in the homeostasis of iron and the different mutations that exist in patients with hereditary hemochromatosis. These control sites may be influenced by gene therapeutic approaches; one general therapy for hemochromatosis of different etiologies is the inhibition of DMT1 synthesis by antisense-generating genes, which has been shown to markedly inhibit apical iron uptake by intestinal epithelial cells. We further discuss the most promising strategies to develop gene vectors and deliver them into enterocytesinfo:eu-repo/semantics/openAccessSociedad de Biología de ChileBiological Research v.39 n.1 20062006-01-01text/htmlhttp://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602006000100014en10.4067/S0716-97602006000100014
institution	Scielo Chile
collection	Scielo Chile
language	English
topic	iron intestine hemochromatosis gene therapy HFE DMT1 cirrhosis
spellingShingle	iron intestine hemochromatosis gene therapy HFE DMT1 cirrhosis EZQUER,FERNANDO NÚÑEZ,MARCO T ROJAS,ALEJANDRO ASENJO,JUAN ISRAEL,YEDY Hereditary hemochromatosis: An opportunity for gene therapy
description	Levels of body iron should be tightly controlled to prevent the formation of oxygen radicals, lipoperoxidation, genotoxicity, and the production of cytotoxic cytokines, which result in damage to a number of organs. Enterocytes in the intestinal villae are involved in the apical uptake of iron from the intestinal lumen; iron is further exported from the cells into the circulation. The apical divalent metal transporter-1 (DMT1) transports ferrous iron from the lumen into the cells, while the basolateral transporter ferroportin extrudes iron from the enterocytes into the circulation. Patients with hereditary hemochromatosis display an accelerated transepithelial uptake of iron, which leads to body iron accumulation that results in cirrhosis, hepatocellular carcinoma, pancreatitis, and cardiomyopathy. Hereditary hemochromatosis, a recessive genetic condition, is the most prevalent genetic disease in Caucasians, with a prevalence of one in 300 subjects. The majority of patients with hereditary hemochromatosis display mutations in the gene coding for HFE, a protein that normally acts as an inhibitor of transepithelial iron transport. We discuss the different control points in the homeostasis of iron and the different mutations that exist in patients with hereditary hemochromatosis. These control sites may be influenced by gene therapeutic approaches; one general therapy for hemochromatosis of different etiologies is the inhibition of DMT1 synthesis by antisense-generating genes, which has been shown to markedly inhibit apical iron uptake by intestinal epithelial cells. We further discuss the most promising strategies to develop gene vectors and deliver them into enterocytes
author	EZQUER,FERNANDO NÚÑEZ,MARCO T ROJAS,ALEJANDRO ASENJO,JUAN ISRAEL,YEDY
author_facet	EZQUER,FERNANDO NÚÑEZ,MARCO T ROJAS,ALEJANDRO ASENJO,JUAN ISRAEL,YEDY
author_sort	EZQUER,FERNANDO
title	Hereditary hemochromatosis: An opportunity for gene therapy
title_short	Hereditary hemochromatosis: An opportunity for gene therapy
title_full	Hereditary hemochromatosis: An opportunity for gene therapy
title_fullStr	Hereditary hemochromatosis: An opportunity for gene therapy
title_full_unstemmed	Hereditary hemochromatosis: An opportunity for gene therapy
title_sort	hereditary hemochromatosis: an opportunity for gene therapy
publisher	Sociedad de Biología de Chile
publishDate	2006
url	http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602006000100014
work_keys_str_mv	AT ezquerfernando hereditaryhemochromatosisanopportunityforgenetherapy AT nunezmarcot hereditaryhemochromatosisanopportunityforgenetherapy AT rojasalejandro hereditaryhemochromatosisanopportunityforgenetherapy AT asenjojuan hereditaryhemochromatosisanopportunityforgenetherapy AT israelyedy hereditaryhemochromatosisanopportunityforgenetherapy
_version_	1718441396522713088

Hereditary hemochromatosis: An opportunity for gene therapy

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