Sphingosine-1-phosphate-induced ERK activation protects human melanocytes from UVB-induced apoptosis

Arch Pharm Res. 2003 Sep;26(9):739-46. doi: 10.1007/BF02976685.

Abstract

Ultraviolet B (UVB) is known to induce apoptosis in human melanocytes. Here we show the cytoprotective effect of sphingosine-1-phosphate (S1P) against UVB-induced apoptosis. We also show that UVB-induced apoptosis of melanocytes is mediated by caspase-3 activation and poly(ADP-ribose) polymerase (PARP) cleavage, and that S1P prevents apoptosis by inhibiting this apoptotic pathway. We further investigated three major mitogen-activated protein (MAP) kinases after UVB irradiation. UVB gradually activated c-Jun N-terminal kinase (JNK) and p38 MAP kinase, while extracellular signal-regulated protein kinase (ERK) was inactivated transiently. Blocking of the p38 MAP kinase pathway using SB203580 promoted cell survival and inhibited the activation of caspase-3 and PARP cleavage. These results suggest that p38 MAP kinase activation may play an important role in the UVB-induced apoptosis of human melanocytes. To explain this cytoprotective effect, we next examined whether S1P could inhibit UVB-induced JNK and p38 MAP kinase activation. However, S1P was not found to have any influence on UVB-induced JNK or p38 MAP kinase activation. In contrast, S1P clearly stimulated the phosphorylation of ERK, and the specific inhibition of the ERK pathway using PD98059 abolished the cytoprotective effect of S1P. Based on these results, we conclude that the activation of p38 MAP kinase plays an important role in UVB-induced apoptosis, and that S1P may show its cytoprotective effect through ERK activation in human melanocytes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anthracenes / pharmacology
  • Apoptosis / drug effects*
  • Apoptosis / physiology
  • Apoptosis / radiation effects*
  • Caspase 3
  • Caspase Inhibitors
  • Caspases / metabolism
  • Caspases / radiation effects
  • Cell Survival / drug effects
  • Cell Survival / physiology
  • Cytoprotection / physiology
  • Dose-Response Relationship, Radiation
  • Enzyme Activation / drug effects
  • Enzyme Activation / physiology
  • Enzyme Activation / radiation effects
  • Flavonoids / pharmacology
  • Humans
  • Imidazoles / pharmacology
  • JNK Mitogen-Activated Protein Kinases
  • Korea
  • Lysophospholipids / antagonists & inhibitors
  • Lysophospholipids / pharmacology*
  • Lysophospholipids / physiology
  • Melanocytes / drug effects*
  • Melanocytes / physiology
  • Melanocytes / radiation effects*
  • Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • Mitogen-Activated Protein Kinases / drug effects*
  • Mitogen-Activated Protein Kinases / metabolism*
  • Mitogen-Activated Protein Kinases / radiation effects
  • Poly(ADP-ribose) Polymerase Inhibitors
  • Poly(ADP-ribose) Polymerases / metabolism
  • Pyridines / pharmacology
  • Sphingosine / analogs & derivatives
  • Sphingosine / antagonists & inhibitors
  • Sphingosine / pharmacology*
  • Sphingosine / physiology
  • Ultraviolet Rays / adverse effects*
  • p38 Mitogen-Activated Protein Kinases

Substances

  • Anthracenes
  • Caspase Inhibitors
  • Flavonoids
  • Imidazoles
  • Lysophospholipids
  • Poly(ADP-ribose) Polymerase Inhibitors
  • Pyridines
  • pyrazolanthrone
  • sphingosine 1-phosphate
  • Poly(ADP-ribose) Polymerases
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases
  • CASP3 protein, human
  • Caspase 3
  • Caspases
  • Sphingosine
  • SB 203580
  • 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one