Faculty Bibliography

Dopachrome tautomerase (DT) (EC 5.3.2.3) is a melanocyte-specific, membrane-associated, heat-labile, non-dialyzable, protease-sensitive factor which catalyzes the isomeric rearrangement of dopachrome to 5,6-dihydroxyindole-2-carboxylic acid (DHICA), apparently through a tautomerization reaction. Metal ions such as Cu, Ni, Co, Zn, Mn, Ca, Al, and Fe can also catalyze the dopachrome/DHICA isomerization. How is the reaction regulated in vivo? An attractive possibility would be that DT is a metalloenzyme. Here we present evidence that this may indeed be the case. Purified preparations of DT and tyrosinase, obtained from Cloudman S91 mouse melanoma cells, were assayed in the presence of a variety of metal chelators including EDTA (predominantly Ca and Mg), EGTA (predominantly Ca), phenylthiourea (PTU) (predominantly Cu), 2,2'-dipyridyl (predominantly Fe); 1,10-phenanthroline (predominantly Fe), and 2,3-dihydroxybenzoic acid (predominantly Fe). In addition, DT activity was assayed in the presence of two non-chelating structural analogs of 1,10-phenanthroline. Results were as follows: (i) iron chelators inhibited DT activity with no effects on tyrosinase activity; (ii) inhibition by the chelators was reversible with the addition of ferrous iron; (iii) 1,10-phenanthroline pre-complexed to ferrous iron was not inhibitory to DT; (iv) non-chelating analogs of phenanthroline were not inhibitory to DT; (v) PTU was inhibitory to tyrosinase but not DT; (vi) Ca2+ and Mg2+ chelators had little effect on either enzyme activity. Finally, studies with glycosylation inhibitors, glycosylase enzymes, and immobilized lectins, indicated that DT is a glycoprotein. The results suggest that DT is a metal-containing glycosylated enzyme, possibly with ferrous iron at its catalytic center

Skin disorders in which a radiograph may detect associated bony changes or abnormalities of calcification are discussed. They are grouped into eight categories: (1) inherited diseases (e.g., alkaptonuria, neurofibromatosis); (2) congenital disorders (e.g., Sturge-Weber and Proteus syndromes); (3) inflammatory conditions (e.g., dermatomyositis, sarcoidosis); (4) infections (e.g., dental sinus, syphilis); (5) neoplasias (e.g., histiocytosis, mastocytosis); (6) drug- and environment-induced (e.g., acroosteolysis, retinoid toxicity); (7) calcinosis cutis; and (8) osteoma cutis. The first part of this review, published in the August 1991 issue of this JOURNAL, dealt with the first two categories; part II discusses categories 3 through 8

Skin disorders in which a radiograph may detect associated bony changes or abnormalities of calcification are discussed. They are grouped into eight categories: (1) inherited diseases (e.g., alkaptonuria, neurofibromatosis); (2) congenital disorders (e.g., Sturge-Weber and Proteus syndromes); (3) inflammatory conditions (e.g., dermatomyositis, sarcoidosis); (4) infections (e.g., dental sinus, syphilis); (5) neoplasias (e.g., histiocytosis, mastocytosis); (6) drug- and environment-induced (e.g., acroosteolysis, retinoid toxicity); (7) calcinosis cutis; and (8) osteoma cutis. Part I of our review discusses the first two categories

Expression of internal receptors for MSH is an important criterion for responsiveness to MSH by Cloudman melanoma cells (Orlow et al: J. Cell. Physiol., 142:129-136, 1990). Here, we show that internal and external receptors for MSH are of identical molecular weights (50-53 kDa) and share common antigenic determinants, indicating a structural relationship between the 2 populations of molecules. The internal receptors co-purified with a sub-cellular fraction highly enriched for small vesicles, many of which were coated. Ultraviolet B light (UVB) acted synergistically with MSH to increase tyrosinase activity and melanin content of cultured Cloudman melanoma cells, consistent with previous findings in the skin of mice and guinea pigs (Bolognia et al: J. Invest. Derm., 92:651-656, 1989). Preceding the rise in tyrosinase activity in cultured cells, UVB elicited a decrease in internal MSH binding sites and a concomitant increase in external sites. The time frame for the UVB effects on MSH receptors and melanogenesis, 48 hours, was similar to that for a response to solar radiation in humans. Together, the results indicate a key role for MSH receptors in the induction of melanogenesis by UVB and suggest a potential mechanism of action for UVB: redistribution of MSH receptors with a resultant increase in cellular responsiveness to MSH