Human melanogenesis is stimulated by diacylglycerol.
The intracellular signal pathways that mediate pigmentation in human skin are unknown. We now report that a diacylglycerol (DAG) analogue 1-oleoyl-2-acetyl-glycerol (OAG) 25-100 microns strikingly increased the melanin content of cultured human melanocytes in a dose dependent manner without altering growth rate. The pigment increase occurred within 24 h, was accompanied by increased incorporation of the melanin precursor L-3,4-dihydroxyphenyl alanine (DOPA), required new protein synthesis, and was completely blocked by the protein kinase C (PKC) inhibitors H-7 and sphingosine. A PKC-inactive DAG isomer had no effect on melanin per cell. These results implicate protein kinase C and its effector DAG in melanogenesis.
Gordon
P R
PR
USDA Human Nutrition Research Center on Aging, Tufts University, Boston, Massachusetts 02111.
Gilchrest
B A
BA
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D004075:Diglycerides / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D005989:Glycerides / Q000494:pharmacology*; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology; D008543:Melanins / Q000096:biosynthesis*; D010879:Piperazines / Q000494:pharmacology; D011493:Protein Kinase C / Q000502:physiology; D012880:Skin Pigmentation / Q000187:drug effects; D013110:Sphingosine / Q000494:pharmacology
D004075:Diglycerides; D005989:Glycerides; D007546:Isoquinolines; D008543:Melanins; D010879:Piperazines; D003609:Dactinomycin; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; C038237:1-oleoyl-2-acetylglycerol; D003513:Cycloheximide; D011493:Protein Kinase C; D013110:Sphingosine