Alcoholism and alcohol liver disease (ALD) are associated with disorders of iron metabolism ranging from iron deficiency anemia to hemochromatosis and siderosis. As the liver is not only the main site of iron storage, but also secretes the major iron transport protein, transferrin, it seems likely that there is an association between the effects of alcohol on liver cells and iron homeostasis, either as a direct result of toxicity, or through some secondary mechanism of modulation. It is the aim of this study, therefore, to investigate the relationships between alcohol, iron (and various transport and storage proteins), and the various liver cell populations, in particular hepatocytes and Kupffer cells. This project focuses on examination of the system in vitro, utilizing specific populations of cells isolated enzymatically from livers of normal and treated animals (rats). The two rat serum isotransferrins will be purified and radiolabelled with iron and iodine and test systems involving suspensions of viable liver cell populations will be set up and validated, in order to study the interactions among iron, transferrin and the various liver cells. Information obtained from these initial suspensions will be used as a basis for more extensive investigations with cell cultures. In addition to the use of cultured cells in the presence of ethanol, the system will be perturbed through alterations in iron availability, changes in the media constituents and by the addition of endotoxins. The possible cell:cell interactions will also be tested by using """"""""conditioned media"""""""" from one cell population to influence specific aspects of iron metabolism in other types of cells, or by direct co-culture with two or more cell populations. It is anticipated that extrapolation to the human disease state will be greatly facilitated by these studies and that this will lead to a better understanding of the disturbances of iron metabolism that occurs in alcoholic liver disease, i.e., iron overload and anemia.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project (R01)
Project #
1R01AA006860-01
Application #
3110250
Study Section
Alcohol Biomedical Research Review Committee (ALCB)
Project Start
1986-03-01
Project End
1989-02-28
Budget Start
1986-03-01
Budget End
1987-02-28
Support Year
1
Fiscal Year
1986
Total Cost
Indirect Cost
Name
Mount Sinai School of Medicine
Department
Type
Schools of Medicine
DUNS #
City
New York
State
NY
Country
United States
Zip Code
10029
Zhang, H; Loney, L A; Potter, B J (1993) Effect of chronic alcohol feeding on hepatic iron status and ferritin uptake by rat hepatocytes. Alcohol Clin Exp Res 17:394-400
Zhang, H; Potter, B J (1992) The effect of ethanol metabolism on ferritin uptake by freshly isolated rat hepatocytes: is acetaldehyde responsible for this alteration? Alcohol Clin Exp Res 16:301-7
Potter, B J; McHugh, T A; Beloqui, O (1992) Iron uptake from transferrin and asialotransferrin by hepatocytes from chronically alcohol-fed rats. Alcohol Clin Exp Res 16:810-5
Sorrentino, D; Potter, B J; Berk, P D (1990) From albumin to the cytoplasm: the hepatic uptake of organic anions. Prog Liver Dis 9:203-24
Berk, P D; Potter, B J; Sorrentino, D et al. (1990) Hepatocellular fatty acid uptake is mediated by a plasma membrane fatty acid binding protein closely related to mitochondrial glutamic oxaloacetic transaminase. Ann N Y Acad Sci 585:379-85
Okuda, H; Potter, B J; Blades, B et al. (1989) Dose-related effects of phenobarbital on hepatic glutathione-S-transferase activity and ligandin levels in the rat. Drug Metab Dispos 17:677-82
Potter, B J; Blades, B; McHugh, T A et al. (1989) Effects of endotoxin on iron uptake by the hepatocyte. Am J Physiol 257:G524-31
Potter, B J; Sorrentino, D; Berk, P D (1989) Mechanisms of cellular uptake of free fatty acids. Annu Rev Nutr 9:253-70
Schwieterman, W; Sorrentino, D; Potter, B J et al. (1988) Uptake of oleate by isolated rat adipocytes is mediated by a 40-kDa plasma membrane fatty acid binding protein closely related to that in liver and gut. Proc Natl Acad Sci U S A 85:359-63
Potter, B J; Stump, D; Schwieterman, W et al. (1987) Isolation and partial characterization of plasma membrane fatty acid binding proteins from myocardium and adipose tissue and their relationship to analogous proteins in liver and gut. Biochem Biophys Res Commun 148:1370-6

Showing the most recent 10 out of 12 publications