Keratinization is a specialized and orderly differentiation process which commences in keratinocytes no longer engaged in cell division. While structural characteristics of each stage of keratinization at both light and electron microscopic levels have been documented comprehensively, chemical and functional aspects of the morphologic hallmarks require further investigation in order to advance our scientific understanding of normal and abnormal keratinization. In this project, chemical properties of nuclear proteins wich result in morphological abnormalities of the nucles in epidermal cells will be investigated by immunoelectron microscopy. How the distribution of nuclear proteins changes in epidermal cells undergoing normal and pathological keratinization will be analyzed. Similarly, immunohistochemical techniques will be used to dissect, at the chemical and molecular levels, individual constituents of submicroscopic structures such as keratohyalin granules, keratinosomes, desmosome complexes, etc. Questions to be asked include: a) where do these molecules localize in cells at different degree of maturation, and b) how do they change under pathological circumstances. The roles of epidermal enzymes in the hydrolysis of proteins in the differentiation of the nucleus and cytoplasm will also be determined biochemically. Protein products resulting from both limited proteolysis and interactions of enzymes and inhibitors will be demonstrated. Finally, bioactivities of proteins in differentiated keratinocytes will be elucidated as enzyme regulators and/or anti-microbial agents. The methodology and basic information obtained in normal skin will be applied to diseases such as psoriasis, ichthyosis and verrucae. The resulting information will be utilized to improve understanding of pathomechanisms of the diseases.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37AR012433-21
Application #
3481383
Study Section
General Medicine A Subcommittee 2 (GMA)
Project Start
1976-04-15
Project End
1991-03-31
Budget Start
1988-04-01
Budget End
1989-03-31
Support Year
21
Fiscal Year
1988
Total Cost
Indirect Cost
Name
University of California San Francisco
Department
Type
Schools of Medicine
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Cuzzi-Maya, T; Sidbury, R; Epstein, W L et al. (1998) Thrombomodulin expression on dermal cells in normal and psoriatic skin. Arch Dermatol Res 290:233-9
Larabell, C A; Fukuyama, K; Epstein, W L (1993) Desmosome differentiation during epidermal cornification: new observations obtained from intermediate voltage electron microscopy. J Invest Dermatol 101:103-4
Hara, K; Fukuyama, K; Sakai, H et al. (1993) Purification and immunohistochemical localization of aspartic proteinases in rat epidermis. J Invest Dermatol 100:394-9
Takahara, H; Zaidi, S I; Mukhtar, H et al. (1993) Purification and characterization of NADPH-cytochrome P-450 reductase from rat epidermis. J Cell Biochem 53:206-12
Shimozuma, M; Drew, W L; Miner, R C et al. (1992) Direct inactivation of herpes simplex virus type-2 by rat epidermal protein. Antiviral Res 18:179-89
Ohno, J; Fukuyama, K; Epstein, W L (1990) Glycoconjugate expression of cells of human anagen hair follicles during keratinization. Anat Rec 228:1-6
Hirayama, K; Fukuyama, K; Epstein, W L (1990) Angiotensin II-producing proteases from granulomatous tissue reaction in mice infected with Schistosoma mansoni. Comp Biochem Physiol B 96:553-7
Kashima, M; Takahashi, H; Shimozuma, M et al. (1989) Candidacidal activities of proteins partially purified from rat epidermis. Infect Immun 57:186-90
Ohno, J; Fukuyama, K; Epstein, W L (1989) Dynamic changes of cell-surface glycoconjugates in human palmar epidermis following friction-blisters. Cell Tissue Res 258:403-8
Ohno, J; Fukuyama, K; Hara, A et al. (1989) Immuno- and enzyme-histochemical detection of phosphoprotein phosphatase in rat epidermis. J Histochem Cytochem 37:629-34

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