The effect of aging on the chemical and physical properties of hyaluronic acid and dermatan sulfate from human skin has not been studied. By using viscometry and discontinuous polyacrylamide gel electrophoresis, the mol. wt. of these molecules from the dermis of female fetuses, stillborns, 20-40 and 60-80 year olds will be determined. The non-reducing termini of hyaluronic acid will be studied with Beta-glucuronidase and Beta-N-acetylhexosaminidase; those of dermatan sulfate will be determined with the same exoglycosidases, plus Alpha-L-iduronidase. The polydispersities of hyaluronic and dermatan sulfate will be investigated by high pressure liquid or ion exchange chromatography. Dermatan sulfate from the same age groups will be analyzed for GlcUA/IdUA ratios, degree or sulfation, sulfate location and protein linkage. The protein that binds dermatan sulfate covalently will be isolated in 6M urea at 60 degrees C and characterized with respect to N-terminal and C-terminal amino acids, total carbohydrate and amino acid content, SH groups, disulfide bonds, and molecular weight. Antibodies to the dermatan sulfate-protein complex will be developed and used to study the association of dermatan sulfate with collagens (Type I, III, and IV) by immunoelectron microscopy. Dermal fibroblasts cultures will be established as a source of hyaluronic acid and dermatan sulfate, which will be analyzed as indicated above. The data obtained will elucidate: (a) the chemical and physical properties of hyaluronic acid and dermatan sulfate from female skin, (b) the role of these glycosaminoglycans in aging of the skin, (c) the nature of the dermatan sulfate-carrier protein, (d) association of dermatan sulfate with collagen (Type I, III, and IV) from newborns and adult dermis.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG003877-03
Application #
3114869
Study Section
General Medicine A Subcommittee 2 (GMA)
Project Start
1983-09-29
Project End
1987-06-11
Budget Start
1985-09-01
Budget End
1987-06-11
Support Year
3
Fiscal Year
1985
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
Longas, M O; Bhuyan, D K; Bhuyan, K C et al. (1993) Dietary vitamin E reverses the effects of ultraviolet light irradiation on rat skin glycosaminoglycans. Biochim Biophys Acta 1156:239-44
Longas, M O (1990) Partial characterization of dermatan sulfate by proton nuclear magnetic resonance spectroscopy. Anal Biochem 187:355-8
Longas, M O; Russell, C S; He, X Y (1987) Evidence for structural changes in dermatan sulfate and hyaluronic acid with aging. Carbohydr Res 159:127-36
Longas, M O; Wisch, P; Lebwohl, M G et al. (1986) Glycosaminoglycans of skin and urine in pseudoxanthoma elasticum: evidence for chondroitin 6-sulfate alteration. Clin Chim Acta 155:227-36
Longas, M O; Russell, C S; He, X Y (1986) Chemical alterations of hyaluronic acid and dermatan sulfate detected in aging human skin by infrared spectroscopy. Biochim Biophys Acta 884:265-9
Longas, M O; Fleischmajer, R (1985) Immunoelectron microscopy of proteodermatan sulfate in human mid-dermis. Connect Tissue Res 13:117-25