Immunological analysis of beta-thalassemic mouse intestinal proteins reveals up-regulation of sucrase-isomaltase in response to iron overload.
Maintenance of iron homeostasis must balance the demand for iron due to heme synthesis, which is driven by hematopoiesis, and the restricted intestinal uptake of iron, which otherwise limits absorption of this toxic element. The consequences of perturbed iron homeostasis are witnessed in inherited forms of beta-thalassemia in which erythroid hyperplasia results in enhanced intestinal iron absorption despite tissue iron overload. To gain a better understanding of intestinal factors that are induced when iron homeostasis is disrupted, a panel of monoclonal antibodies that recognize intestinal microvillous membrane proteins of the beta-thalassemic Hbbd(th3)/Hbbd(th3) mouse was established. The monoclonal antibodies were screened by differential Western blotting against normal and beta-thalassemic mouse intestine to identify antigens modulated in the disease state. Here we report the initial characterization of one immunoreactive species that is up-regulated in beta-thalassemic mouse intestine and the tentative identification of this antigen as sucrase-isomaltase. Studies in Caco-2 cells revealed the rather unexpected finding that expression of this intestinal hydrolase is increased in response to iron toxicity.
Akompong
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Department of Nutrition, Harvard School of Public Health, Boston, MA 02115, USA.
Ramm
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E
Chang
C
C
Yu
Z K
ZK
Wessling-Resnick
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M
D000818:Animals; D000911:Antibodies, Monoclonal; D015152:Blotting, Northern; D015153:Blotting, Western; D018938:Caco-2 Cells; D006706:Homeostasis; D006801:Humans; D007408:Intestinal Absorption; D007422:Intestines / Q000201:enzymology*; D007501:Iron / Q000378:metabolism; D019190:Iron Overload / Q000201:enzymology*; D051379:Mice; D008810:Mice, Inbred C57BL; D013394:Sucrase-Isomaltase Complex / Q000378:metabolism*; D017086:beta-Thalassemia / Q000201:enzymology*
D000911:Antibodies, Monoclonal; D007501:Iron; D013394:Sucrase-Isomaltase Complex