Mechanism of regulation of human epidermal transglutaminase.

The activity of crude human epidermal transglutaminase was enhanced remarkably following 24 hr preincubation at low pH (pH 4.5), whereas the pure human epidermal transglutaminase did not show enhancement of enzyme activity at low pHs. Preincubation of pure transglutaminase with rat liver lysosomal fractions (100 microgram/ml) caused a time-dependent enhancement of activity at pH 4.5, up to 4.5 times of the initial activity. This enhancement was specific for lysosomal fractions among the several rat liver subcellular fractions tested. The activity of purified transglutaminase stimulated by lysosomal fractions was inhibited by pepstatin (50 microgram/ml), chymostatin (50 microgram/ml) and EDTA (1 mM). Preincubation of purified transglutaminase with 5 to 100 microgram/ml cathepsin D caused a time-dependent enhancement of activity up to 9.5-fold over control. This enhancement was specific for cathepsin D among the several lysosomal enzymes tested. These in vitro observations suggest possible activation mechanisms of epidermal transglutaminase in vivo. Epidermal transglutaminase may be activated by lysosomal acid proteinases, such as cathepsin B1 and cathepsin D, which are released and activated during the autolytic stages in granular layer in epidermis.