The effects of calcium D-pantetheine-S-sulfonate (PaSSO3Ca) on human pigmen
tation were examined by in vitro assays using two types of human melanocyte
s: normal adult melanocytes (HNM) and M4Be melanoma cells. The compound, wh
en added to a culture medium at doses indicating no cytotoxicity, causes a
visually recognizable, reversible loss of pigment in both types of cells, D
etermination of melanin content, incorporation of C-14-DOPA into melanins a
nd tyrosinase activities demonstrated that treatment of these cells with Pa
SSO3Ca resulted in a marked decrease in all three areas. When homogenates o
f these cells were assayed with lectins, the glycosylation pattern was modi
fied, as tyrosinase activities were reduced in the cells treated with the c
ompound. Immunoprecipitation of tyrosinase and tyrosinase-related protein 1
(Tyrp1 or TRP1) in cells incubated with radioactive glucosamine disclosed
that glucosamine uptake by these enzymes was apparently increased, suggesti
ng structural alterations in their sugar moieties, It is also noted that Pa
SSO3Ca is analogous in its chemical structure to Coenzyme A (CoA), which pl
ays an important role in the intracellular transport of proteins. Based on
these findings, it is likely that the compound exerts its depigmenting effe
cts in human pigment cells through the modification of glycosylation of tyr
osinase and TRP1, which are key enzymes for melanogenesis.