Abstract

The purpose of the proposed study is to investigate 3 newly discovered, unique defects in band 3, the major anion transport and acid-base balance protein. One of the defects represents a recognized autosomal recessive disease and is associated with ion and glucose transport abnormalities and a serious progressive neuropsychiatric disorder (familial amyotrophic chorea with acanthocytosis). Another disease presents biochemically and immunologically as accelerated aging of young and middle aged red blood cells. The reticulocyte count is -20%. The third disease is characterized by acanthocytosis and increase anion transport. It is called """"""""high- molecular weight band 3"""""""" because there is an addition of several peptides in the anion transport region. Band 3 is a ubiquitous protein. Like the RBC proteins spectrin, ankyrin, 4.1, and actin, it is present in brain and all other cells examined.
The specific aims of this project are to (1) determine what functional defects are associated with band 3 structural defects; (2) define the structural defects in terms of band 3 domains and amino acid sequence; (3) determine alterations in DNA sequence of the band 3 gene of affected individuals by sequencing regions of the gene which correspond to regions of the protein which appear altered in the peptide maps of the patient's band 3 proteins; (4) determine the mode of inheritance of band 3 defects in kindreds; (5) identify other defects in band 3 in the population.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG008444-04
Application #
3120064
Study Section
Neurological Sciences Subcommittee 1 (NLS)
Project Start
1989-07-12
Project End
1992-07-31
Budget Start
1991-08-01
Budget End
1992-07-31
Support Year
4
Fiscal Year
1991
Total Cost
Indirect Cost

  Institution

Name
University of Arizona
Department
Type
Schools of Medicine
DUNS #
City
Tucson
State
AZ
Country
United States
Zip Code
85721

  Publications

Poulin, J E; Cover, C; Gustafson, M R et al. (1996) Vitamin E prevents oxidative modification of brain and lymphocyte band 3 proteins during aging. Proc Natl Acad Sci U S A 93:5600-3
Kay, M M; Lake, D; Cover, C (1995) Band 3 and its peptides during aging, radiation exposure, and Alzheimer's disease: alterations and self-recognition. Adv Exp Med Biol 383:167-93
Salhany, J M; Schopfer, L M; Kay, M M et al. (1995) Differential sensitivity of stilbenedisulfonates in their reaction with band 3 HT (Pro-868-->Leu). Proc Natl Acad Sci U S A 92:11844-8
Goodman, J R; Gamble, D; Kay, M M (1994) Distribution and function of multiple anion transporter proteins in brain tumor cell lines in relation to glucose transport. Brain Res Bull 33:411-7
Kay, M M (1994) Regulatory autoantibody and cellular aging and removal. Adv Exp Med Biol 347:161-92
Kay, M M; Bosman, G; Johnson, R C et al. (1994) Molecular basis of human band-3 mutation associated with increased anion transport. Exp Clin Immunogenet 11:209-21
Kay, M M; Wyant, T; Goodman, J (1994) Autoantibodies to band 3 during aging and disease and aging interventions. Ann N Y Acad Sci 719:419-47
Kay, M M (1993) Generation of senescent cell antigen on old cells initiates IgG binding to a neoantigen. Cell Mol Biol (Noisy-le-grand) 39:131-53
Bruce, L J; Kay, M M; Lawrence, C et al. (1993) Band 3 HT, a human red-cell variant associated with acanthocytosis and increased anion transport, carries the mutation Pro-868-->Leu in the membrane domain of band 3. Biochem J 293 ( Pt 2):317-20
Marchalonis, J J; Schluter, S F; Wilson, L et al. (1993) Natural human antibodies to synthetic peptide autoantigens: correlations with age and autoimmune disease. Gerontology 39:65-79

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