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Lysophospholipase A2 activity in guinea-pig heart microsomal fractions displaying high activities with 2-acylglycerophosphocholines with linoleic and arachidonic acids.

ABSTRACT: Lysophospholipases A1 which catalyse the hydrolysis of acyl groups from 1-acylglycerophosphocholine (GPC) have been characterized in a number of mammalian tissues and do not exhibit any acyl specificity. In the present study lysophospholipase activity in guinea-pig heart microsomes (microsomal fractions) that hydrolyses 2-acyl-GPC was detected and characterized. The enzyme showed a high degree of acyl specificity. The relative rates of hydrolysis of individual 2-acyl-GPCs with different fatty acids was as follows: C18:2/C20:1/C18:1/C16:0, 14:6:1:1. When substrates were presented in pairs, the hydrolysis of each substrate by the enzyme was inhibited, but to very different extents. Of each pair of lysolipids examined (2-arachidonoyl- and 2-palmitoyl-GPC; 2-arachidonoyl- and 2-linoleoyl-GPC), the one with the expected higher rate of hydrolysis was more severely inhibited and the degree of inhibition was dependent on the concentration of the other lysolipid. The characteristics of the lysophospholipase A2 suggest the enzyme could work in concert with phospholipase A1 to release arachidonic and linoeic acids for further metabolism. The properties of lysophospholipase A2 and A1 suggest that they are different enzymes.

SUBMITTER: Arthur G

PROVIDER: S-EPMC1138864 | biostudies-other | 1989 Jul

REPOSITORIES: biostudies-other

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2-acyl-sn-glycero-3-phosphoethanolamine lysophospholipase A2 activity in guinea-pig heart microsomes.

Project description:We have recently described a lysophospholipase A2 activity in guinea-pig heart microsomes that hydrolyses 2-acyl-sn-glycero-3-phosphocholine (2-acyl-GPC). The presence of a similar activity that hydrolyses 2-acyl-sn-glycero-3-phosphoethanolamine (2-acyl-GPE) was not known. In this study, a lysophospholipase A2 activity in guinea-pig heart microsomes that hydrolyses 2-acyl-GPE has been characterized. The enzyme did not require Ca2+ for activity and exhibited a high specificity for 2-arachidonoyl-GPE and 2-linoleoyl-GPE over 2-oleoyl-GPE and 2-palmitoyl-GPE. The specificity for these unsaturated substrates was observed in the presence and absence of detergents. Selective hydrolysis of 2-arachidonoyl-GPE over 2-palmitoyl-GPE was observed when equimolar quantities of the two substrates were incubated with the enzyme. There was no preferential hydrolysis of either 2-linoleoyl- or 2-arachidonoyl-GPE when presented individually or as a mixture. Significant differences in the characteristics of 2-acyl-GPE-hydrolysing and 2-acyl-GPC-hydrolysing activities included differences in their optimum pH, the effect of Ca2+ and their acyl specificities. Taken together, these results suggest that the two activities are catalysed by different enzymes. 2-Acyl-GPE lysophospholipase activity with a preference for 2-arachidonoyl-GPE over 2-oleoyl-GPE was observed in guinea-pig brain, liver, kidney and lung microsomes. Lysophospholipase A1 activity that catalyses the hydrolysis of 1-acyl-GPE was also present in guinea-pig heart microsomes and had different characteristics from the 2-acyl-GPE-hydrolysing activity, including a preference for saturated over unsaturated substrates. The 2-acyl-GPE lysophospholipase A2 activity appeared to be distinct from Ca(2+)-independent phospholipase A2. The characteristics of the 2-acyl-GPE lysophospholipase A2 suggest it could play a role in the selective release of arachidonic and linoleic acids for further metabolism in cells.

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Modulation of arachidonic and linoleic acid metabolites in myeloperoxidase-deficient mice during acute inflammation.

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Project description:Linoleic acid (LA) is an essential omega-6 polyunsaturated fatty acid (PUFA) derived from the diet. Sebocytes, whose primary role is to moisturise the skin, process free fatty acids (FFAs) to produce the lipid-rich sebum. Importantly, like other sebum components such as palmitic acid (PA), LA and its derivative arachidonic acid (AA) are known to modulate sebocyte functions. Given the different roles of PA, LA and AA in skin biology, the aim of this study was to assess the specificity of sebocytes for LA and to dissect the different roles of LA and AA in regulating sebocyte functions. Using RNA sequencing, we confirmed that gene expression changes in LA-treated sebocytes were largely distinct from those induced by PA. LA, but not AA, regulated the expression of genes related to cholesterol biosynthesis, androgen and nuclear receptor signalling, keratinisation, lipid homeostasis and differentiation. In contrast, a set of mostly down-regulated genes involved in lipid metabolism and immune functions overlapped in LA- and AA-treated sebocytes. Lipidomic analyses revealed that the changes in the lipid profile of LA-treated sebocytes were more pronounced than those of AA-treated sebocytes, suggesting that LA may serve not only as a precursor of AA but also as a potent regulator of sebaceous lipogenesis, which may not only influence the gene expression profile but also have further specific biological relevance. In conclusion, we have shown that sebocytes are able to respond selectively to different lipid stimuli and that LA-induced effects can be both AA-dependent and independent. Our findings allow for the consideration of LA application in the therapy of sebaceous gland-associated inflammatory skin diseases such as acne, where lipid modulation and selective targeting of AA metabolism are potential treatment options.

| S-EPMC10420848 | biostudies-literature

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