Protein kinase C activation in rat colonic mucosa after diets differing in their fatty acid composition

The effects of an n-3 PUFA-enriched diet on cardiac cell membrane phospholipid fraction compositions and associated protein kinase-C (PKC) translocation modification have never been studied in higher mammals. This is of importance since membrane fatty acid composition has been shown to influence PKC signalling pathways. In the present study, we have tested whether the incorporation of n-3 PUFA in cardiac membrane phospholipids correlated with changes in the fatty acid composition of diacylglycerols (DAG) and led to a differential translocation of PKC isoforms. Two groups of five dogs were fed the standard diet supplemented with palm oil or fish oil for 8 weeks. Dogs fed a fish oil-enriched diet showed a preferential incorporation of EPA and, to a lesser extent, of DHA, at the expense of arachidonic acid, in the circulating TAG, plasma phospholipids, erythrocyte phospholipids and cardiomyocyte phospholipid fractions. Analysis of 1,2-DAG fatty acid composition also indicated a preferential enrichment of EPA compared with DHA. Associated with these results, a reduction in the expression of PKC-δ and PKC-ε isoforms in the particulate fractions was observed whereas no effect was seen for PKC-α and PKC-ζ. We conclude that a fish oil-enriched diet induces a modification in fatty acid composition of cardiac membrane phospholipids, associated with a differential translocation of PKC isoforms. These results can be explained by the production of structurally different DAG that may participate in some of the protective effects of n-3 PUFA against various chronic diseases.

Download Full-text

Phospholipid fatty acid composition and protein kinase C activity in the large intestine of rats fed on butter and coconut-oil diets

British Journal Of Nutrition ◽

10.1017/s0007114599001658 ◽

1999 ◽

Vol 82 (5) ◽

pp. 411-418 ◽

Cited By ~ 7

Author(s):

Anne-Maria Pajari ◽

Marja Mutanen

Keyword(s):

Fatty Acid Composition ◽

Protein Kinase C ◽

Fatty Acid ◽

Protein Kinase ◽

Acid Composition ◽

Phospholipid Fatty Acid ◽

Saturated Fat ◽

Coconut Oil ◽

Phospholipid Fatty Acid Composition ◽

Kinase C

Protein kinase C (PKC) has been proposed to play an important role in the aetiology of colon cancer. Therefore, we investigated whether the amount and type of saturated fat could affect colonic PKC activity by modifying either mucosal phospholipid fatty acid composition or faecal diacylglycerol production. Male Wistar rats (n 13 per group) were fed on diets containing butter or coconut oil at energy levels of 10 % and 43 % for 4 weeks. The control group received a low-fat diet providing 10 % of energy from sunflowerseed oil. PKC activity was higher in the distal than the proximal colon but the quantity or type of fat did not alter PKC activity in either region of the colon. Saturated fats caused moderate changes in the fatty acid composition of caecal phospholipids, which were more obvious in the phosphatidylethanolamine than in the phosphatidylcholine fraction. A significant correlation was found between fatty acid composition of phosphatidylcholine and membrane PKC activity. In particular, there was a positive correlation between the proportion of saturated 14:0 and 18:0 and increased PKC activity while unsaturated 18:2n-6, 20:4n-6 and 16:1n-7 were inversely correlated with PKC activity. No relationship was found between phosphatidylethanolamine fatty acids and PKC activity. Concentration of faecal diacylglycerol was not affected by the diet. Overall the data suggest that diets high in saturated fat may not alter colonic PKC activity to a significant extent.

Download Full-text

Synergistic action of diacylglycerol and unsaturated fatty acid for protein kinase C activation: its possible implications.

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.88.12.5149 ◽

1991 ◽

Vol 88 (12) ◽

pp. 5149-5153 ◽

Cited By ~ 189

Author(s):

T. Shinomura ◽

Y. Asaoka ◽

M. Oka ◽

K. Yoshida ◽

Y. Nishizuka

Keyword(s):

Protein Kinase C ◽

Fatty Acid ◽

Protein Kinase ◽

Unsaturated Fatty Acid ◽

Synergistic Action ◽

Kinase C ◽

Protein Kinase C Activation

Download Full-text

Phosphatidylcholine-dependent protein kinase C activation. Effects of cis-fatty acid and diacylglycerol on synergism, autophosphorylation and Ca2+-dependency

Biochemical Journal ◽

10.1042/bj2840221 ◽

1992 ◽

Vol 284 (1) ◽

pp. 221-226 ◽

Cited By ~ 17

Author(s):

S G Chen ◽

D Kulju ◽

S Halt ◽

K Murakami

Keyword(s):

Protein Kinase C ◽

Fatty Acid ◽

Protein Kinase ◽

Acid Activation ◽

Type Iii ◽

Kinase C ◽

Synergistic Activation ◽

Protein Kinase C Activity ◽

Fatty Acid Activation ◽

Protein Kinase C Activation

A long-chain neutral phospholipid, dioleoylphosphatidylcholine, was found to support protein kinase C activation by cis-fatty acid and diacylglycerol (DAG). This effect of phosphatidylcholine (PC) is totally dependent on the presence of cis-fatty acid; PC greatly stimulates the cis-fatty acid-induced protein kinase C activity, but it does not activate protein kinase C at all, even in the presence of DAG, if cis-fatty acid is absent. DAG, however, plays a modulatory role in the presence of Ca2+; it further enhances the PC-potentiated cis-fatty acid activation of protein kinase C. Although the activities of all three protein kinase C subtypes tested (types I, II and III) are supported by this PC mechanism, type III is most sensitive to the DAG effect, and it is activated synergistically by cis-fatty acid and DAG. The potency of PC to support the synergistic activation of this subtype is equivalent to that of phosphatidylserine (PS). There are several differences, however, between PC- and PS-supported synergism observed in type III protein kinase C: (1) Ca(2+)-sensitivity is different; PC requires higher concentrations of Ca2+ (10-20 microM-Ca2+) than those required for PS (micromolar Ca2+); (2) PC/cis-fatty acid/DAG-induced autophosphorylation of protein kinase C subtypes (types I, II and III) is very weak, whereas PS/cis-fatty acid/DAG strongly stimulate autophosphorylation of these subtypes under the conditions at which both PC and PS systems fully activate the protein kinase C in terms of histone phosphorylation. These observations suggest that a neutral phospholipid such as PC may also participate in the activation and differential regulation of protein kinase C.

Download Full-text

Synergistic activation of type III protein kinase C by cis-fatty acid and diacylglycerol

Biochemical Journal ◽

10.1042/bj2820033 ◽

1992 ◽

Vol 282 (1) ◽

pp. 33-39 ◽

Cited By ~ 47

Author(s):

S G Chen ◽

K Murakami

Keyword(s):

Protein Kinase C ◽

Fatty Acid ◽

Protein Kinase ◽

Second Messengers ◽

Type I ◽

Physiological Concentration ◽

Type Iii ◽

Kinase C ◽

Synergistic Activation ◽

Protein Kinase C Activation

Micromolar concentrations of cis-fatty acid synergistically activate type III protein kinase C with diacylglycerol. This synergistic effect occurs at low concentrations of cis-fatty acid and diacylglycerol, and it is capable of inducing almost full activation of this protein kinase C subtype at a physiologically relevant Ca2+ concentration (2 microM). The synergistic activation mode can be observed even in the absence of Ca2+, but micromolar Ca2+ significantly enhances the type III protein kinase C activation. cis-Fatty acid also augments the diacylglycerol-induced activation of other subtypes (type I and II), although the effect is smaller than that observed in type III. Neither the diacylglycerol- nor the cis-fatty acid-dependent mode of activation can fully activate any of these subtypes at a physiological concentration of Ca2+ (2 microM). Our results suggest that the generation of three second messengers, i.e. the increase in intracellular Ca2+ concentration and the generation of both cis-fatty acid and diacylglycerol in the cell, may be necessary signals for protein kinase C activation, particularly for type III protein kinase C.

Download Full-text