Substitution of 15(S)hydroxyeicosatetraenoic acid in phosphatidylinositol alters the growth of liver epithelial cells.
We investigated the substitution of 15(S)-hydroxyeicosatetraenoic acid (15(S)HETE) in phospholipid signaling pathways and its consequences on the growth of non-transformed (NT-) and spontaneously transformed (T-) rat liver epithelia cells (RLEC). 15(S)HETE was selectively incorporated into the sn-2 position of phosphatidylinositol (PI) and at a higher rate into T-RLEC. RLEC rapidly mobilized the resulting 15(S)HETE-containing PI (15(S)HETE-PI) and produced 1-acyl,2-[1(S)HETE]-glycerol. Although total diacylglycerol levels were similar in both cell types, the ratio 1-acyl,2-[15(S)HETE]-glycerol / 15(S)HETE-PI was higher in NT-RLEC, suggesting a lower mobilization of 15(S)HETE-PI in T-RLEC. Using rat brain protein kinase C, 1-stearoyl,2-[15(S)HETE]-glycerol was as potent an in vitro protein kinase C activator as 1-stearoyl,2-arachidonoyl-glycerol. Finally, selective substitution of 15(S)HETE in PI altered DNA synthesis in T-RLEC: whereas low concentrations of 15(S)HETE (1 nM and 10 nM) in these cells were mitogenic, higher concentrations resulted in a 30% inhibition of DNA synthesis.
Vernhet
L
L
Laboratoire de Pharmacologie Moléculaire, Faculté des Sciences Pharmaceutiques et Biologiques, Université de Rennes I, France.
Sobo
G
G
Wang
J
J
Gueddari
A
A
Oates
J A
JA
Legrand
A B
AB
D000818:Animals; D001921:Brain / Q000201:enzymology; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002461:Cell Line, Transformed; D004789:Enzyme Activation; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects; D006893:Hydroxyeicosatetraenoic Acids / Q000737:chemistry*; D008099:Liver / Q000166:cytology / Q000187:drug effects*; D010716:Phosphatidylinositols / Q000737:chemistry / Q000502:physiology*; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats
D006893:Hydroxyeicosatetraenoic Acids; D010716:Phosphatidylinositols; C025984:15-hydroxy-5,8,11,13-eicosatetraenoic acid; D011493:Protein Kinase C