Protectin D1

Protectin D1
Names
	Preferred IUPAC name (4Z,7Z,10R,11E,13E,15Z,17S,19Z)-10,17-Dihydroxydocosa-4,7,11,13,15,19-hexaenoic acid
	Other names 10R,17S-Dihydroxy-docosa-4Z,7Z,11E,13E,15Z,19Z-hexaenoate; 10R,17S-Dihydroxy-docosa-4Z,7Z,11E,13E,15Z,19Z-hexaenoic acid; Neuroprotectin D1
Identifiers
CAS Number	660430-03-5 ;
3D model (JSmol)	Interactive image;
ChemSpider	13171083 ;
PubChem CID	16042541;
UNII	P3FX063KLI ;
CompTox Dashboard (EPA)	DTXSID101031663 ;
	InChI InChI=1S/C22H32O4/c1-2-3-10-15-20(23)17-12-8-9-13-18-21(24)16-11-6-4-5-7-14-19-22(25)26/h3,5-13,17-18,20-21,23-24H,2,4,14-16,19H2,1H3,(H,25,26)/b7-5-,9-8+,10-3-,11-6-,17-12-,18-13+/t20-,21+/m0/s1 Key: CRDZYJSQHCXHEG-SFVBTVKNSA-N ;
	SMILES O=C(O)CC\C=C/C/C=C\C[C@@H](O)\C=C\C=C\C=C/[C@@H](O)C\C=C/CC;
Properties
Chemical formula	C22H32O4
Molar mass	360.4871 g/mol
Density	1.049 g/cm3
Boiling point	559.379 °C (1,038.882 °F; 832.529 K)
Solubility in water	0.0069
log P	4.95
Acidity (pKa)	4.82
	Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). Infobox references

Protectin D1 also known as neuroprotectin D1 (when it acts in the nervous system) and abbreviated most commonly as PD1 or NPD1 is a member of the class of specialized proresolving mediators. Like other members of this class of polyunsaturated fatty acid metabolites, it possesses strong anti-inflammatory, anti-apoptotic and neuroprotective activity. PD1 is an aliphatic acyclic alkene 22 carbons in length with two hydroxyl groups at the 10 and 17 carbon positions and one carboxylic acid group at the one carbon position.^[1]

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.^[1] 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.^[2]^[3]

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.^[2]^[3]^[4]^[5] 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.^[6]^[7]

^ ^a ^b Ariel A, Li PL, Wang W, Tang WX, Fredman G, Hong S, Serhan CN (October 2010). "The docosatriene protectin D1 is produced by TH2 skewing and promotes human T cell apoptosis via lipid raft clustering". J. Biol. Chem. 280 (52): 43079–43086. doi:10.1074/jbc.M509796200. PMID 16216871.
^ ^a ^b Mukherjee PK, Marcheselli VL, Serhan CN, Bazan NG (June 2004). "Neuroprotectin D1: a docosahexaenoic acid-derived docosatriene protects human retinal pigment epithelial cells from oxidative stress". Proc. Natl. Acad. Sci. USA. 101 (22): 8491–8496. doi:10.1073/pnas.0402531101. PMC 420421. PMID 15152078.
^ ^a ^b Calandria JM, Marcheselli VL, Mukherjee PK, Uddin J, Winkler JW, Petasis NA, Bazan NG (April 2009). "Selective survival rescue in 15-lipoxygenase-1-deficient retinal pigment epithelial cells by the novel docosahexaenoic acid-derived mediator, neuroprotectin D1". J. Biol. Chem. 284 (26): 17877–17882. doi:10.1074/jbc.M109.003988. PMC 2719426. PMID 19403949.
^ Antony R, Lukiw WJ, Bazan NG (April 2010). "Neuroprotectin D1 induces dephosphorylation of Bcl-xL in a PP2A-dependent manner during oxidative stress and promotes retinal pigment epithelial cell survival". J. Biol. Chem. 285 (24): 18301–18308. doi:10.1074/jbc.M109.095232. PMC 2881755. PMID 20363734.
^ Zhao Y, Calon F, Julien C, Winkler JW, Petasis NA, Lukiw WJ, Bazan NG (January 2011). "Docosahexaenoic acid-derived neuroprotectin D1 induces neuronal survival via secretase-and PPARγ-mediated mechanisms in Alzheimer's disease models". PLOS ONE. 6 (1): e15816. Bibcode:2011PLoSO...615816Z. doi:10.1371/journal.pone.0015816. PMC 3016440. PMID 21246057.
^ García-Sastre A (July 2013). "Lessons from Lipids in the Fight against Influenza". Cell. 154 (1): 22–23. doi:10.1016/j.cell.2013.06.024. PMID 23827671.
^ Morita M, Kuba K, Ichikawa A, Nakayama M, Katahira J, Iwamoto R, Imai Y (March 2013). "The lipid mediator protectin D1 inhibits influenza virus replication and improves severe influenza". Cell. 153 (1): 112–125. doi:10.1016/j.cell.2013.02.027. PMID 23477864.

[lipidraft-1] Ariel A, Li PL, Wang W, Tang WX, Fredman G, Hong S, Serhan CN (October 2010). "The docosatriene protectin D1 is produced by TH2 skewing and promotes human T cell apoptosis via lipid raft clustering". J. Biol. Chem. 280 (52): 43079–43086. doi:10.1074/jbc.M509796200. PMID 16216871.

[oxidativestress-2] Mukherjee PK, Marcheselli VL, Serhan CN, Bazan NG (June 2004). "Neuroprotectin D1: a docosahexaenoic acid-derived docosatriene protects human retinal pigment epithelial cells from oxidative stress". Proc. Natl. Acad. Sci. USA. 101 (22): 8491–8496. doi:10.1073/pnas.0402531101. PMC 420421. PMID 15152078.

[survivalrescue-3] Calandria JM, Marcheselli VL, Mukherjee PK, Uddin J, Winkler JW, Petasis NA, Bazan NG (April 2009). "Selective survival rescue in 15-lipoxygenase-1-deficient retinal pigment epithelial cells by the novel docosahexaenoic acid-derived mediator, neuroprotectin D1". J. Biol. Chem. 284 (26): 17877–17882. doi:10.1074/jbc.M109.003988. PMC 2719426. PMID 19403949.

[dephosphorylation-4] Antony R, Lukiw WJ, Bazan NG (April 2010). "Neuroprotectin D1 induces dephosphorylation of Bcl-xL in a PP2A-dependent manner during oxidative stress and promotes retinal pigment epithelial cell survival". J. Biol. Chem. 285 (24): 18301–18308. doi:10.1074/jbc.M109.095232. PMC 2881755. PMID 20363734.

[neuronalsurvival-5] Zhao Y, Calon F, Julien C, Winkler JW, Petasis NA, Lukiw WJ, Bazan NG (January 2011). "Docosahexaenoic acid-derived neuroprotectin D1 induces neuronal survival via secretase-and PPARγ-mediated mechanisms in Alzheimer's disease models". PLOS ONE. 6 (1): e15816. Bibcode:2011PLoSO...615816Z. doi:10.1371/journal.pone.0015816. PMC 3016440. PMID 21246057.

[influenza-6] García-Sastre A (July 2013). "Lessons from Lipids in the Fight against Influenza". Cell. 154 (1): 22–23. doi:10.1016/j.cell.2013.06.024. PMID 23827671.

[virusreplication-7] Morita M, Kuba K, Ichikawa A, Nakayama M, Katahira J, Iwamoto R, Imai Y (March 2013). "The lipid mediator protectin D1 inhibits influenza virus replication and improves severe influenza". Cell. 153 (1): 112–125. doi:10.1016/j.cell.2013.02.027. PMID 23477864.

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