sPLA2-X stimulates cutaneous melanocyte dendricity and pigmentation through a lysophosphatidylcholine-dependent mechanism.
Photoprotection of the skin is provided by melanocytes, neural crest derived cells that synthesize melanin in specialized organelles that are transferred to keratinocytes. Secretory phospholipases comprise a large family of Ca2+-dependent enzymes that liberate arachidonic acid (AA), a precursor of prostaglandins, as well as lysophospholipids. The predominant secretory phospholipase expressed by keratinocytes is group X secretory phospholipase A2 (sPLA2), which liberates large amounts of AA and the lysophospholipid lysophosphatidylcholine (LPC), from membrane preparations. Recent work by our laboratory has shown that melanocytes express receptors for prostaglandins that upon activation stimulate melanocyte dendricity and activity of tyrosinase, a key enzyme in melanin biosynthesis. In the present study, we have treated human melanocytes with recombinant sPLA2-X and show that low levels of sPLA2-X stimulate both tyrosinase activity and melanocyte dendricity. We found that the effects of sPLA2-X are mediated predominantly by LPC, not AA, and we have demonstrated expression of the phospholipase A2 receptor and two G-protein-coupled receptors for LPC (G2A and GPR119) in human melanocytes. Because secretory phospholipases are released during inflammation and are regulated by UV irradiation, our data suggest an important role for sPLA2-X in cutaneous pigmentation through the release of LPC.
Scott
Glynis A
GA
Department of Dermatology, University or Rochester School of Medicine and Dentistry, Rochester, New York 14642, USA. glynis_scott@urmc.rochester.edu
Jacobs
Stacey E
SE
Pentland
Alice P
AP
D016718:Arachidonic Acid / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000378:metabolism; D049109:Cell Proliferation; D054509:Group X Phospholipases A2; D006801:Humans; D008244:Lysophosphatidylcholines / Q000378:metabolism*; D008544:Melanocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D014442:Monophenol Monooxygenase / Q000378:metabolism; D010741:Phospholipases A / Q000494:pharmacology*; D054467:Phospholipases A2; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D054507:Receptors, Phospholipase A2; D012867:Skin / Q000166:cytology / Q000187:drug effects; D012880:Skin Pigmentation
D018797:Cell Cycle Proteins; C115270:G2A receptor; D008244:Lysophosphatidylcholines; C516360:PLA2R1 protein, human; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D054507:Receptors, Phospholipase A2; D016718:Arachidonic Acid; D014442:Monophenol Monooxygenase; D010741:Phospholipases A; D054509:Group X Phospholipases A2; C516365:PLA2G10 protein, human; D054467:Phospholipases A2