Induction of ornithine decarboxylase in T/C-28a2 chondrocytes by lysophosphatidic acid: signaling pathway and inhibition of cell proliferation.
Among several extracellular messengers tested, lysophosphatidic acid (LPA) was able to cause the most marked induction of ornithine decarboxylase (ODC) in serum-starved human T/C-28a2 chondrocytes. LPA also induced the activation/phosphorylation of Src, Akt and p44/42 MAPK, and the translocation of PKC-delta from cytosol to membrane coupled to its tyrosine phosphorylation. Experiments with selective signaling inhibitors indicate that LPA leads to Src activation through Gi protein-coupled receptors. In turn Src can activate PI3K and PKC-delta, and all these signaling proteins are required for ODC induction. In conclusion these results show that chondrocytes may be a novel target for LPA action. However, although LPA is considered a mitogen for several cell types and ODC induction is generally correlated to cell growth, LPA was not able to stimulate chondrocyte growth, but rather exerted an anti-proliferative effect.
Facchini
Annalisa
A
Dipartimento di Biochimica G. Moruzzi, University of Bologna, Italy.
Borzì
Rosa Maria
RM
Flamigni
Flavio
F
D002455:Cell Division / Q000502:physiology*; D002461:Cell Line, Transformed; D019902:Chondrocytes / Q000201:enzymology*; D004789:Enzyme Activation; D004790:Enzyme Induction; D006801:Humans; D008246:Lysophospholipids / Q000502:physiology*; D009955:Ornithine Decarboxylase / Q000096:biosynthesis*; D011493:Protein Kinase C / Q000378:metabolism; D051745:Protein Kinase C-delta; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D015398:Signal Transduction; D019061:src-Family Kinases / Q000378:metabolism
D008246:Lysophospholipids; D011518:Proto-Oncogene Proteins; D019061:src-Family Kinases; C494918:AKT1 protein, human; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; C497258:PRKCD protein, human; D011493:Protein Kinase C; D051745:Protein Kinase C-delta; D009955:Ornithine Decarboxylase; C032881:lysophosphatidic acid