In vitro activation of mouse skin protein kinase C by fatty acids and their hydroxylated metabolites

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Abstract
To understand how dietary fatty acids differentially modulate mouse skin tumorigenesis, the ability of specific fatty acids and their derivatives to activate murine epidermal protein kinase C (PKC)in vitro was investigated. Total PKC from untreated female SSIN mouse skin was partially purified and incubated with specific fatty acids at concentrations up to 300 μM in the presence of Ca2+ and phosphatidylserine. Thecis-unsaturated fatty acids tested, ranging from 16∶1 to 22∶6, stimulated PKC activity in a similar dose-dependent manner with an approximate threefold maximum increase over control. Neither the number ofcis-double bonds nor the chainlength of these fatty acids affected their relative ability to activate PKC.trans-Fatty acids, with the exception of linoelaidic acid (t,t-18∶2n−6), exhibited about half of the potency of their correspondingcis-isomers in stimulating PKC at the plateau concentration (200 μM) or lower. Substitutions close to the double bond oncis-fatty acids abolished their ability to activate PKC. The hydroxylated metabolites of arachidonic acid (20∶4n−6) and linoleic acid (c,c-18∶2n−6), i.e., the hydroxyeicosatetraenoic acids (HETE) and hydroxyoctadecadienoic acids (HODE), also activated mouse skin PKCin vitro, but only about half as effectively as did the respective parent fatty acids. The results suggest that both hydroxyl substitution andtrans-configuration of HETE and HODE are responsible for their reduced ability to activate PKC. Overall the data suggests that the reduced skin tumor yield observed in mice fed diets high inc,c-18∶2n−6 is not likely to be due to differences in the ability ofc,c-18∶2n−6 or 20∶4n−6, or their matabolites, to activate PKC.