Glucocorticoid regulation of phospholipid turnover and protein kinase C activity in mouse hepatoma 22 cells.
Glucocorticoids induce growth inhibition in certain sensitive hepatoma cells. To investigate how glucocorticoids interact with growth-factor-dependent pathways, we studied the effects of dexamethasone (Dex) on the DNA synthesis, protein kinase C (PKC) activity and phospholipid turnover in mouse hepatoma 22 cells. Dex was found to reduce DNA synthesis in slowly growing hepatoma cells, whereas exponentially growing cells were Dex-insensitive. Direct measurements of PKC activity in the hormone-sensitive hepatoma 22 cells showed a rapid inhibition (within 30 min) when treated with Dex. Dex addition to hormone-sensitive but not to hormone-insensitive hepatoma 22 cells for 30 min caused a significant decrease of 32P-incorporation into the major cellular phospholipids: phosphatidylcholine, phosphatidylglycerol and phosphoinositides. At the same time, the analysis of the correlation between changes in PKC activity and phospholipid turnover showed that synthesis of phosphatidylcholine and phosphatidylglycerol was under positive control of PKC activity. The data suggest that suppression of phospholipid turnover in hormone-sensitive hepatoma 22 cells is one of the early events caused by glucocorticoids, whereas the decrease of PKC activity induced by the hormone is mediated, probably, via changes in phospholipid metabolism.
Krasil'nikov
M A
MA
Laboratory of Tumor Biochemistry, All-Union Cancer Research Center, USSR Academy of Medical Sciences, Moscow.
Bezrukov
V M
VM
Shatskaya
V A
VA
D000818:Animals; D001345:Autoradiography; D004261:DNA Replication / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology*; D007700:Kinetics; D008114:Liver Neoplasms, Experimental / Q000378:metabolism*; D051379:Mice; D010710:Phosphates / Q000378:metabolism; D010743:Phospholipids / Q000302:isolation & purification / Q000378:metabolism*; D010761:Phosphorus Radioisotopes; D011493:Protein Kinase C / Q000378:metabolism*; D013936:Thymidine / Q000378:metabolism; D014407:Tumor Cells, Cultured
D010710:Phosphates; D010743:Phospholipids; D010761:Phosphorus Radioisotopes; D003907:Dexamethasone; D011493:Protein Kinase C; D013936:Thymidine