Depigmenting effects of calcium D-pantetheine-S-sulfonate on human melanocytes.
The effects of calcium D-pantetheine-S-sulfonate (PaSSO3Ca) on human pigmentation were examined by in vitro assays using two types of human melanocytes: normal adult melanocytes (HNM) and M4Be melanoma cells. The compound, when added to a culture medium at doses indicating no cytotoxicity, causes a visually recognizable, reversible loss of pigment in both types of cells. Determination of melanin content, incorporation of 14C-DOPA into melanins and tyrosinase activities demonstrated that treatment of these cells with PaSSO3Ca resulted in a marked decrease in all three areas. When homogenates of these cells were assayed with lectins, the glycosylation pattern was modified, as tyrosinase activities were reduced in the cells treated with the compound. 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, suggesting structural alterations in their sugar moieties. It is also noted that PaSSO3Ca is analogous in its chemical structure to Coenzyme A (CoA), which plays an important role in the intracellular transport of proteins. Based on these findings, it is likely that the compound exerts its depigmenting effects in human pigment cells through the modification of glycosylation of tyrosinase and TRP1, which are key enzymes for melanogenesis.
Franchi
J
J
LVMH Branche Parfums et Cosmétiques, Laboratoires Recherche et Développement, Saint Jean de Brave, France. jfranchi@diormail.com
Coutadeur
M C
MC
Marteau
C
C
Mersel
M
M
Kupferberg
A
A
D015153:Blotting, Western; D003065:Coenzyme A / Q000378:metabolism; D004295:Dihydroxyphenylalanine / Q000378:metabolism; D006031:Glycosylation; D006801:Humans; D015151:Immunoblotting; D008543:Melanins / Q000378:metabolism; D008544:Melanocytes / Q000187:drug effects* / Q000378:metabolism; D008545:Melanoma / Q000188:drug therapy / Q000378:metabolism; D008562:Membrane Glycoproteins; D014442:Monophenol Monooxygenase / Q000378:metabolism; D010088:Oxidoreductases; D010204:Pantetheine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D010858:Pigmentation / Q000187:drug effects*; D011506:Proteins / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects
D008543:Melanins; D008562:Membrane Glycoproteins; D011506:Proteins; D010204:Pantetheine; D004295:Dihydroxyphenylalanine; C000354:bifidus factor; D010088:Oxidoreductases; C489799:TYRP1 protein, human; C064056:tyrosinase-related protein-1; D014442:Monophenol Monooxygenase; D003065:Coenzyme A