Masae Takahashi

Division of Functional Food Chemistry

Summary of the research
1. Epidermis has a barrier function against microorganisms. Cells of the stratum corneum which is the outer layer of the epidermis have thick membrane, cornified envelope. Cornified envelope is formed at the terminal differentiation of keratinocytes and it contains several proteins such as cystatin A. Cystatin A is a cysteine protease inhibitor and exist specifically in epidermis. It inhibits the activity of cysteine protease from Staphylococcus aureus V8 and the growth of this bacterium. Cornified envelope also inhibits the growth of Staphylococcus aureus V8. Therefore, the thick membrane has an important role as a physical and chemical barrier. Cystatin A is one of component proteins of keratohyalin granules, which are also related substance of the terminal differentiation of keratinocytes, as well as cornified envelope. Caspase 14 that is a specific caspase in epidermis is reported that its location is keratohyalin granules. This is one of cysteine proteases, so cystatin A might
control its activity. We will investigate the mechanism of epidermal terminal differentiation related with caspase 14 and cystatin A.

2. Senile xerosis is one of the characteristics of aged skin. This may be caused by a decrease in the stratum corneum free amino acids which are natural moisturizing factors (NMF). Though the stratum corneum free amino acids are NMF, we observed that the amounts of free amino acids in the stratum corneum of xerosis increased. This finding suggests that pyrrolidone carboxylic acid, other NMF, might have more important role than free amino acids. Therefore, the amount of pyrrolidone carboxylic acid will be compared between young and aged epidermis and the properties of its synthesis enzyme will be investigated.

Selected Papers
1. Takahashi M, Tezuka T, Katunuma N: Phosphorylated cystatin α is a natural substrate of epidermal transglutaminase for formation of skin cornified envelope. FEBS Lett 308: 79-82, 1992.

2. Takahashi M, Tezuka T, Korant B, Katunuma N: Inhibition of cysteine protease and growth of Staphylococcus aureus V8 and poliovirus by phosphorylated cystatin α conjugate of skin. BioFactors 10: 339-345, 1999.

3. Takahashi M, Horiuchi Y, Tezuka T: Presence of bactericidal/permeability- increasing protein in human and rat skin. Exp Dermatol 13:55-60, 2004.

4. Takahashi M, Tezuka T: The content of free amino acids in the stratum corneum is increased in senile xerosis. Arch Dermatol Res 295: 448-452, 2004.

5. Takahashi M, Horiuchi Y, Tezuka T: Large hematoxylin-stainable keratohyalin granules in solar keratoses -Immunohistochemical comparison using anti-Ted-H-1 antibody and anti-loricrin antibody-. Br J Dermatol 153: 976-980, 2005.

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