Enzymatic and free radical oxidation are common reactions of almost all biomolecules. Polyunsaturated fatty acids (PUFAs), including arachidonic acid (AA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), are the main targets of such modifications because they are the principal repository of oxidizable double bonds. Oxygenated lipids are collectively known as oxylipins. Eicosanoids, including prostaglandins and leukotrienes derived from AA, are best studied and represent one of the most biologically important groups of oxylipins in mammals. They are biologically active lipids implicated in various pathological processes, such as atherothrombosis, inflammation, and cancer. The biosynthesis of oxygenated eicosanoids is the result of the coordinated action of several enzymatic activities, from phospholipases that release the PUFAs from membrane phospholipids to primary oxidative enzymes, such as cyclooxygenases and lipoxygenases, to isomerases, synthases, and hydrolases that carry out the final biosynthetic steps of the biologically active metabolites. Oxylipins also include oxygenated derivatives of EPA and DHA, and some of them are termed "specialized pro-resolving mediators" (SPM) that were suggested to be involved in resolving inflammation. The production of prostanoids, leukotrienes, and SPM occurs in single cells or a complex manner by transcellular biosynthesis through the cooperation of multiple different types of cells in the tissues.
Also, cytochrome P450 (CYP) enzymes, a superfamily of heme-containing monooxygenases, catalyze hydroxylation and epoxidation of PUFAs such as AA yielding 20-hydroxyeicosatetraenoic acid (20-HETE) and epoxyeicosatrienoic acids (EpETrE); both are implicated in blood pressure regulation and inflammation. Oxylipins can be bound in several lipids, such as oxidized phospholipids (oxPL), endocannabinoids and cholesteryl esters (CE). Enzymatically oxidized phospholipids (eoxPL) are pro-coagulants and promote different actions in leukocytes and platelets.
This research topic aims to collect manuscripts on:
1) Appropriate methodologies, validation strategies, and pitfalls of the techniques used to assess oxylipins or oxylipin-containing lipids in biological samples.
2) Description of proper experimental models in vitro to assess the regulation of their biosynthesis and inhibition.
3) The characterization of innovative pharmacological strategies to affect the different pathways.
4) Evidence of their biological roles in inflammation-driven pathologies in animals and humans.
Enzymatic and free radical oxidation are common reactions of almost all biomolecules. Polyunsaturated fatty acids (PUFAs), including arachidonic acid (AA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), are the main targets of such modifications because they are the principal repository of oxidizable double bonds. Oxygenated lipids are collectively known as oxylipins. Eicosanoids, including prostaglandins and leukotrienes derived from AA, are best studied and represent one of the most biologically important groups of oxylipins in mammals. They are biologically active lipids implicated in various pathological processes, such as atherothrombosis, inflammation, and cancer. The biosynthesis of oxygenated eicosanoids is the result of the coordinated action of several enzymatic activities, from phospholipases that release the PUFAs from membrane phospholipids to primary oxidative enzymes, such as cyclooxygenases and lipoxygenases, to isomerases, synthases, and hydrolases that carry out the final biosynthetic steps of the biologically active metabolites. Oxylipins also include oxygenated derivatives of EPA and DHA, and some of them are termed "specialized pro-resolving mediators" (SPM) that were suggested to be involved in resolving inflammation. The production of prostanoids, leukotrienes, and SPM occurs in single cells or a complex manner by transcellular biosynthesis through the cooperation of multiple different types of cells in the tissues.
Also, cytochrome P450 (CYP) enzymes, a superfamily of heme-containing monooxygenases, catalyze hydroxylation and epoxidation of PUFAs such as AA yielding 20-hydroxyeicosatetraenoic acid (20-HETE) and epoxyeicosatrienoic acids (EpETrE); both are implicated in blood pressure regulation and inflammation. Oxylipins can be bound in several lipids, such as oxidized phospholipids (oxPL), endocannabinoids and cholesteryl esters (CE). Enzymatically oxidized phospholipids (eoxPL) are pro-coagulants and promote different actions in leukocytes and platelets.
This research topic aims to collect manuscripts on:
1) Appropriate methodologies, validation strategies, and pitfalls of the techniques used to assess oxylipins or oxylipin-containing lipids in biological samples.
2) Description of proper experimental models in vitro to assess the regulation of their biosynthesis and inhibition.
3) The characterization of innovative pharmacological strategies to affect the different pathways.
4) Evidence of their biological roles in inflammation-driven pathologies in animals and humans.