Modification of protein kinase C (PKC) activity and diacylglycerol (DAG) accumulation in hepatocytes in continuous endotoxemia.
On the basis of our work, the status of PKC-mediated signal transduction in hepatocytes in chronic endotoxemia can be summarized as follows: 1. Vasopressin (10(-8) M)-induced DAG accumulation is delayed and reduced by 50%, as compared with the response of cells of saline-infused rats. 2. Under basal conditions, total PKC activity (cytosol + pellet) is elevated due to a tendency for higher cytosolic fractional activity. 3. Both TPA- and hormonally-induced (in response to VP and PE) translocation are impaired. 4. Quantitative receptor autoradiography reveals a selective decrease in [3H-PDBu] binding sites in hepatic membranes. We conclude that modulation in endotoxemia of the DAG signal elicited by VP stimulation in hepatocytes could lead to altered transmembrane control of PKC-mediated protein phosphorylation, thereby contributing to the mechanism of impairments in the regulation of cellular metabolism.
Department of Physiology, Louisiana State University Medical Center, New Orleans 70112.
J A
JA
Spitzer
I V
IV
Deaciuc
E B
EB
Rodriguez de Turco
B L
BL
Roth
J B
JB
Hermiller
J P
JP
Mehegan
D000818:Animals; D001692:Biological Transport; D003600:Cytosol / Q000201:enzymology; D004075:Diglycerides / Q000378:metabolism*; D004731:Endotoxins / Q000097:blood / Q000494:pharmacology*; D005989:Glycerides / Q000378:metabolism*; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010656:Phenylephrine / Q000494:pharmacology; D015240:Phorbol 12,13-Dibutyrate / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014667:Vasopressins / Q000494:pharmacology
D004075:Diglycerides; D004731:Endotoxins; D005989:Glycerides; D014667:Vasopressins; D010656:Phenylephrine; D015240:Phorbol 12,13-Dibutyrate; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate