ABSTRACT
Kinetic parameters of spontaneous lipid peroxidation (LP) in endoplasmic reticulum (ER) membranes isolated from the liver of healthy mice, tumour-host and ascitic Ehrlich tumour cells have been studied. The LP kinetics was characterized based on the primary LP products, dienic conjugates (DC), and the extent of lipid substrate unsaturation (double bond (DB) concentration per mg lipids). It was shown that the rate constants of DC formation and DB consumption were, respectively, (6.3 +/- 0.7).10(-2) and (4.5 +/- 0.3).10(-2) min-1 in the control; (2.5 +/- 0.3).10(-2) and (1.0 +/- 0.1).10(-2) min-1 in the ER from the tumour-host liver; (1.4 +/- 0.1).10(-2) and (0.38 +/- 0.01).10(-2) min-1 in the ER from the tumour cells. The initial DC and DB levels in membranes of the tumour cells were significantly (2 to 3 times) lower than in the ER isolated from the control liver. There was a correlation between the DB initial level and the constants of DB consumption during LP in vitro for all types of membranes studied.
Subject(s)
Carcinoma, Ehrlich Tumor/metabolism , Intracellular Membranes/metabolism , Lipid Peroxidation , Liver/metabolism , Animals , Endoplasmic Reticulum/ultrastructure , Kinetics , Mice , Microsomes, Liver/metabolismABSTRACT
We studied the effects of 12-O-tetradecanoylphorbol-13-acetate (TPA) and protein kinase C (PKC) in a broad range of concentrations (10(-18)-10(-7) M) on lipid peroxidation (LP) in rat brain plasma membranes. TPA and PKC were shown to inhibit LP, the concentration curves had two maxima at 10(-15) M and 10(-12) M for TPA and at 10(-16) M and 10(-13) M for PKC. The combined action of TPA (10(-12) M) and PKC (10(-16) M) resulted in a synergic inhibition of LP. These data suggest PKC to have two (kinase and antioxidative) enzymatic activities. The properties of TPA as an LP inhibitor (via activation of PKC) and tumour promoter (inhibition of LP is a necessary step of tumour promotion) can be explained based on this suggestion.
