IRON-RESPONSIVE ELEMENT-BINDING PROTEIN IN HEMOCHROMATOSIS LIVER AND INTESTINE

被引:20
作者
FLANAGAN, PR [1 ]
HAJDU, A [1 ]
ADAMS, PC [1 ]
机构
[1] UNIV WESTERN ONTARIO HOSP,DEPT MED,LONDON,ON N6A 5A5,CANADA
关键词
D O I
10.1016/0270-9139(95)90304-6
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Iron-responsive element-binding protein (IRE-BP) activity was studied in liver and intestinal samples of hemochromatosis and control patients using a short P-32-IRE-RNA probe on ''retardation'' nondenaturing polyacrylamide gels. IRE-BP activity was assessed in liver biopsy specimens in 36 patients-16 hemochromatosis homozygotes, 4 hemochromatosis heterozygotes, 6 patients with secondary iron overload, and 10 control patients with normal hepatic iron concentrations. Intestinal IRE-BP activity was assessed in 14 hemochromatosis homozygotes and 16 normal subjects. Endogenous IRE-BP activity was determined from P-32 retarded on the gel, and total IRE-BP activity was assessed after reducing tissue samples with 2-mercaptoethanol. Hepatic endogenous IRE-BP activity was inversely related to hepatic iron concentration (r = -.59, P <.0002). Mean hepatic endogenous IRE-BP activity in the hemochromatosis homozygotes, 0.25 +/- 0.04 pmol/mg protein, was significantly decreased compared with values in the normal controls, 0.45 +/- 0.06 pmol/mg protein, P <.05. Hepatic total IRE-BP was also significantly decreased in the hemochromatosis patients by gel retardation assay and Western blotting with anti-IRE-BP antibody. Intestinal endogenous IRE-BP activity, total IRE-BP activity, and iron concentration did not significantly differ between hemochromatosis patients and normal control subjects. This suggests that both endogenous IRE-BP activity and the total amount of the protein are downregulated in the liver by tissue iron, Intestinal IRE-BP activity that regulates intestinal transferrin receptor expression is normal in hemochromatosis and appropriate for the intracellular iron concentration.
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页码:828 / 832
页数:5
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