Sphingosine 1-phosphate regulates heat shock protein 27 induction by a p38 MAP kinase-dependent mechanism in aortic smooth muscle cells

Exp Cell Res. 1999 Aug 1;250(2):376-80. doi: 10.1006/excr.1999.4536.

Abstract

In an aortic smooth muscle cell line, A10 cells, we investigated the effect of sphingosine 1-phosphate on the induction of heat shock protein 27 (HSP27), a low-molecular-weight heat shock protein. Sphingosine 1-phosphate significantly induced the accumulation of HSP27 in a pertussis toxin-sensitive manner. The effect was dose-dependent in the range between 0.1 and 30 microM. Sphingosine 1-phosphate stimulated an increase in the levels of mRNA for HSP27. Sphingosine 1-phosphate stimulated both p42/p44 mitogen-activated protein (MAP) kinase and p38 MAP kinase activation. PD98059, an inhibitor of the upstream kinase that activates p42/p44 MAP kinase, did not affect sphingosine 1-phosphate-stimulated HSP27 induction. In contrast, SB203580, an inhibitor of p38 MAP kinase, reduced sphingosine 1-phosphate-induced HSP27 induction. SB203580 reduced the levels of mRNA for HSP27 induced by sphingosine 1-phosphate. These results indicate that sphingosine 1-phosphate stimulates the induction of HSP27 via p38 MAP kinase activation in aortic smooth muscle cells.

MeSH terms

  • Animals
  • Aorta
  • Calcium-Calmodulin-Dependent Protein Kinases / antagonists & inhibitors
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
  • Cell Line
  • Dose-Response Relationship, Drug
  • Enzyme Activation / drug effects
  • Flavonoids / pharmacology
  • Gene Expression Regulation / drug effects
  • Heat-Shock Proteins / biosynthesis*
  • Heat-Shock Proteins / genetics
  • Imidazoles / pharmacology
  • Lysophospholipids*
  • Mitogen-Activated Protein Kinase 1 / antagonists & inhibitors
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinases*
  • Muscle, Smooth, Vascular / cytology
  • Muscle, Smooth, Vascular / drug effects
  • Muscle, Smooth, Vascular / enzymology
  • Muscle, Smooth, Vascular / metabolism*
  • Pertussis Toxin
  • Phosphorylation / drug effects
  • Pyridines / pharmacology
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Signal Transduction / drug effects*
  • Sphingosine / analogs & derivatives*
  • Sphingosine / antagonists & inhibitors
  • Sphingosine / pharmacology
  • Virulence Factors, Bordetella / pharmacology
  • p38 Mitogen-Activated Protein Kinases

Substances

  • Flavonoids
  • Heat-Shock Proteins
  • Imidazoles
  • Lysophospholipids
  • Pyridines
  • RNA, Messenger
  • Virulence Factors, Bordetella
  • sphingosine 1-phosphate
  • Pertussis Toxin
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases
  • Sphingosine
  • SB 203580
  • 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one