Clinical reports have attributed the amelioration of chronic inflammatory skin disorders to the presence of certain polyunsaturated fatty acids (PUFA) in dietary oils. To test the hypothesis of a local modulatory effect of these PUFA in the epidermis, the basal diet of normal guinea pigs was supplemented with ethyl esters of either fish oil [rich in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)] or borage oil [rich in gamma-linolenic acid (GLA)]. Our data demonstrated that dietary oils influence the distribution of PUFA in epidermal phospholipids and the epidermal levels of PUFA-derived hydroxy fatty acids. Specifically, animals supplemented with ethyl esters of fish oil markedly incorporated EPA and DHA into epidermal phospholipids, which paralleled the epidermal accumulation of 15-hydroxyeicosapentaenoic acid (15-HEPE) and 17-hydroxydocosahexaenoic acid (17-HDoHE). Similarly, animals supplemented with esters of borage oil preferentially incorporated dihomogammalinolenic acid (DGLA), the epidermal elongase product of GLA, into the epidermal phospholipids, which also was accompanied by epidermal accumulation of 15-hydroxyeicosatrienoic acid (15-HETrE). By factoring the epidermal levels of the 15-lipoxygenase products and their relative inhibitory potencies, we evolved a measure of the overall potential of dietary oils to exert local anti-inflammatory effect. For example, the leukotriene inhibition potentials (LIP) of both fish oil and borage oil were greatly enhanced when compared to controls. Thus, the altered profiles of epidermal 15-lipoxygenase products generated from particular dietary oils may be responsible, at least in part, for reported ameliorative effects of oils on chronic inflammatory skin disorders.
The in vitro incubation of murine keratinocytes in the presence of 1 alpha,25-dihydroxyvitamin D3 enhanced the rapid hydrolysis of the prelabeled keratinocyte polyphosphoinositides (polyPtdIns) when compared to untreated cells. The rapid hydrolysis of the polyPtdIns and the release of the inositol phosphates (particularly InsP3 and InsP2) precede the onset of differentiation of these cells. These data therefore suggest that 1 alpha,25-dihydroxyvitamin D3 functions in vitro to initiate the rapid generation of InsP3 from cellular polyPtdIns; this in turn may mobilize intracellular Ca2+, thus providing the signal which program the murine keratinocytes from a proliferating mode into a differentiating mode.
The metabolism of arachidonate in brain membrane phosphoglycerides was investigated in vivo by intracerebral injection of labeled arachidonate and by in vitro assay of enzymic systems associated with the metabolism. After intracerebral injection, labeled arachidonate was incorporated rapidly into brain phosphoglycerides with radioactivity distributed mainly in diacyl‐sn‐glycero‐3‐phosphoinositols (GPI) and diacyl‐sn‐glycero‐3‐phosphocholines (GPC). Some evidence of a metabolic relationship between diacyl‐sn‐glycerophosphoinositols (diacyl‐GPI) and diacylglycerols was observed. Among the phosphoglycerides labeled with [14C] arachidonoyl groups, diacyl‐GPI were most rapidly metabolized in brain microsomal and synaptosomal fractions. The decay of diacyl‐GPI in brain synaptosomes may be represented by two pools with half‐lives of 5 hr and 5 days. Three types of enzymic systems related to metabolism of the polyunsaturated fatty acids in brain were investigated. The first system involves the cyclic events relating the ATP‐dependent activation of polyunsaturated fatty acids (PUFA) to their acylCoA by the acylCoA ligase and subsequent hydrolysis of acylCoA to free fatty acids by the acylCoA hydrolase. It is apparent that fatty acid activation and hydrolysis is under strigent control in order to maitain suitable levels of free fatty acids and acylCoA in the brain tissue for various metabolic use. Factors involved in the regulation may include the level of ATP, divalent cations and the nature of substrates. The second enzymic system pertains to deacylation via phospholipase A2 and reacylation via the acyltransferase of membrane phosphoglycerides. In brain tissue, activity of the acyl transferase is generally higher than that of the phospholipase A2. Factors known to affect specificity of the acyltransferase include substrate concentration and the nature of the acyl groups and lysophosphoglycerides. The acyltranferase(s) in brain preferentially transfers arachidonate to 1‐acyl‐GPI. Activity of the acyltransferase can be inhited by a number of lypophilic compounds including local anesthetics and cell surface agents. Activity of the phospholipase A2 in brain may depend on the physical form of the substrates, i.e., whether the substrates are in monomeric or micellar form. The third process is associated with the degradation of diacyl‐GPI by enzymes present in brain subcellular membranes. Incubation of brain subcellular membranes with 1‐acyl‐2‐[14C] arachidonoyl‐GPI yielded labeled diacylglycerols and arachidonate. The phospholipase C action is specific for hydrolysis of diacyl‐GPI. The arachidonate released from incubation of labeled diacyl‐GPI may be the result of phospholipase A2 action which is not specific for diacyl‐GPI or the hydrolysis by lipase acting on the diacylglycerols formed from the phospholipase C activity. Enzymic hydrolysis of diacyl‐GPI is most active in the microsomal fraction, but uoon disruption of synaptosomes, enzyme in synaptic plasma membranes is also active in degradating this glycerophospholipid. In general, the results of in vitro studies are in good agreement with those observed in vivo and the information yielded has contributed towards understanding the metabolism of polyunsaturated fatty acids in brain subcellular membranes.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.