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|Section2= }} Protectin D1 also known as neuroprotectin D1 (when it acts in the nervous system) and abbreviated most commonly as PD1 or NPD1 is an organic biomolecule with strong anti-inflammatory, anti-apoptotic and neuroprotective activity. PD1 is an aliphatic acyclic alkene with two hydroxyl groups at the 10 and 17 carbon positions and one carboxylic acid group at the one carbon position. Specifically, PD1 is an endogenous stereoselective lipid mediator classified as an autocoid protectin. Autacoids are enzymatically derived chemical mediators with distinct biological activities and molecular structures. Protectins are signaling molecules that are produced enzymatically from unsaturated fatty acids. Their molecular structure is characterized by the presence of a conjugated system of double bonds.〔 PD1, like other protectins, is produced by the oxygenation of the ω-3 polyunsaturated fatty acid docosahexaenoic acid (DHA) and it is found in many tissues, such as the retina, the lungs and the nervous system. PD1 has a significant role as an anti-inflammatory, anti-apoptotic and neuroprotective molecule. Studies in Alzheimer's disease animal models, in stroke patients and in human retina pigment epithelial cells (RPE) have shown that PD1 can potentially reduce inflammation induced by oxidative stress and inhibit the pro-apoptotic signal, thereby preventing cellular degeneration.〔〔 Finally, recent studies examining the pathogenicity of influenza viruses, including the avian flu (H5N1), have suggested that PD1 can potentially halt the proliferation of the virus, thus protecting respiratory cells from lethal viral infections. ==Biosynthesis of PD1== In vivo, PD1 is mainly produced as a response to inflammatory signals and it is found in various tissues, such as the retina pigment epithelial cells, lung epithelial cells, peripheral blood mononuclear cells (PBMC) and neural tissues. Studies in PBMC have shown that endogenous DHA, the main precursor of PD1, is released by the activity of phospholipase A2.〔〔〔 According to these studies, PD1 is preferentially synthesized in PBMC cells skewed to the Type 2 T helper cell phenotype (TH2).〔 This suggests that T-cell differentiation plays an important role in the activation of the PD1 biosynthetic pathway. The interaction of PBMC with interleukin 4 (IL-4), a potent inflammatory signal, leads to the differentiation of PBMC to TH2 type lymphocytes.〔 In addition, activated TH2 cells further release IL-4, leading to the up-regulation of the enzyme 15-lipoxygenase-1 (15-LO-1).〔 15-LO-1 is a non-heme iron-carrying dioxygenase that adds oxygen atoms in a stereospecific manner on free and esterified ω-3 polyunsaturated fatty acids like DHA.〔 Overall, the biosynthesis of PD1 proceeds through three distinct steps throughout which the activity of 15-LO-1 is essential. In the first step of the biosynthetic pathway, the binding of 15-LO-1 to its substrate (DHA) leads to the formation of the (17''S'')-hydro(peroxy)-DHA intermediate. This intermediate is rapidly processed to form a 16(17)-epoxide-containing molecule, which is the second intermediate. Finally, in the third step of the pathway, enzymatic hydrolysis of the 16(17)-epoxide-containing intermediate leads to the formation of PD1.〔 抄文引用元・出典: フリー百科事典『 ウィキペディア(Wikipedia)』 ■ウィキペディアで「Protectin D1」の詳細全文を読む スポンサード リンク
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