Nutritional modulation of guinea pig skin hyperproliferation by essential fatty acid deficiency is associated with selective down regulation of protein kinase C-beta.
In a previous study we demonstrated that 13-hydroxyoctadecadienoic acid (13-HODE), a 15-lipoxygenase metabolite of linoleic acid is incorporated into epidermal phosphatidyl 4,5-bisphosphate (PtdIns 4,5-P2) and released as 13-HODE-containing-diacylglycerol (13-HODE-DAG). In vitro, 13-HODE-DAG was shown to selectively inhibit epidermal total protein kinase C (PKC-beta) activity. To determine whether these observations are relevant in vivo, guinea pigs were made essential fatty acid deficient (EFAD) by feeding them a basal diet supplemented with 4% hydrogenated coconut oil for 8 wk. Tissue levels of putative 13-HODE-DAG, protein kinase C (PKC) isozymes and tissue hyperproliferation were determined in the epidermal preparations from skin of control safflower oil-fed guinea pigs, those fed EFAD diet and those fed EFAD diet followed by the control diet for 2 wk. Our data revealed that cutaneous 13-HODE and 13-HODE-DAG were significantly lower in EFAD animals than in safflower-fed controls. These reductions were associated with both elevated epidermal hyperproliferation and elevated expressions and activities of PKC-alpha and beta-isozymes. Refeeding the animals with safflower oil for 2 wk replenished tissue levels of 13-HODE-DAG, which inversely correlated with the selective down regulation of PKC-beta expression and activity and the reversal of hyperproliferation. In contrast, although, the expression and activity of PKC-alpha was elevated in the epidermis of the EFAD guinea pigs, this elevated PKC-alpha expression was not down regulated after refeeding the safflower oil diet to the animals.(ABSTRACT TRUNCATED AT 250 WORDS)
D000824:Animal Nutritional Physiological Phenomena; D000818:Animals; D015153:Blotting, Western; D002455:Cell Division / Q000502:physiology; D000074263:Coconut Oil; D003059:Cocos; D004032:Diet / Q000592:standards; D004041:Dietary Fats / Q000494:pharmacology; D004075:Diglycerides / Q000032:analysis / Q000378:metabolism / Q000502:physiology; D015536:Down-Regulation; D005228:Fatty Acids, Essential / Q000172:deficiency* / Q000502:physiology; D006168:Guinea Pigs; D007527:Isoenzymes / Q000032:analysis / Q000235:genetics / Q000502:physiology; D019787:Linoleic Acid; D008041:Linoleic Acids / Q000032:analysis / Q000172:deficiency / Q000378:metabolism / Q000502:physiology; D008297:Male; D010938:Plant Oils / Q000494:pharmacology; D011493:Protein Kinase C / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D012450:Safflower Oil / Q000494:pharmacology; D015398:Signal Transduction / Q000502:physiology; D012867:Skin / Q000737:chemistry / Q000166:cytology* / Q000378:metabolism
D004041:Dietary Fats; D004075:Diglycerides; D005228:Fatty Acids, Essential; D007527:Isoenzymes; D008041:Linoleic Acids; D010938:Plant Oils; C024348:13-hydroxy-9,11-octadecadienoic acid; D012450:Safflower Oil; D019787:Linoleic Acid; D011493:Protein Kinase C; D000074263:Coconut Oil