TY - JOUR
T1 - Induction of ornithine decarboxylase in T/C-28a2 chondrocytes by lysophosphatidic acid
T2 - Signaling pathway and inhibition of cell proliferation
AU - Facchini, Annalisa
AU - Borzì, Rosa Maria
AU - Flamigni, Flavio
PY - 2005/5/23
Y1 - 2005/5/23
N2 - 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-δ 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-δ, 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.
AB - 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-δ 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-δ, 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.
KW - Cell proliferation
KW - Chondrocytes
KW - Lysophosphatidic acid
KW - Ornithine decarboxylase
KW - Signal transduction
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U2 - 10.1016/j.febslet.2005.04.044
DO - 10.1016/j.febslet.2005.04.044
M3 - Article
C2 - 15890344
AN - SCOPUS:19444375130
VL - 579
SP - 2919
EP - 2925
JO - FEBS Letters
JF - FEBS Letters
SN - 0014-5793
IS - 13
ER -