Mediator derived

Mediators derived from activated plasma protein cascades Complement system... 

D1 (10,17S-docosatriene) from DHA using tandem liquid chromatography-photodiode array-electrospray ionization-tandem mass spectrometry (LC-PDA-ESI-MS-MS)-based lipidomic analysis have been documented in ischemic brain [4] and retinal pigment epithelium [5], This new lipid is called neuroprotectin D1 (1) because of its neuro-protectiveproperties in brain ischemia-reperfusion [4] and in oxidative stress-challenged retinal pigment epithelial cells [5] (2) because of its potent ability to inactivate proapoptotic signaling (see apoptosis, Ch. 35) [5] and (3) because it is the first identified neuroprotective mediator derived from DHA. 

Figure 8.9 Prostaglandins and leukotrienes are potent eicosanoid lipid mediators, derived from phospholipase-released arachidonic acids, that are involved in numerous homeostatic biological functions and inflammation. They are generated by cyclooxygenase isozymes and 5-lipoxygenase, respectively, and their biosynthesis and pharmacological actions are inhibited by clinically relevant nonsteroidal anti-inflammatory drugs.

Prostanoid mediators derived from arachidonic acid and sites of drug action. ASA, acetylsalicylic acid (aspirin) LT, leukotriene NSAID, nonsteroidal... 

Lastly, eicosanoids are important pro-inflammatory mediators derived from membrane metabolism. PLA2 plays a key role in the production of eicosanoids, derived from arachi-donic acid of the phospholipids contained in the cell membrane (40,41). As mentioned earlier, arachidonic acid is liberated from the membrane-bound phospholipids by several forms of PLA2 and is the substrate for COX-1, COX-2, and 12-lipoxygenases (LOX) involved in vascular inflammation. 

Fig. 13. (A) ORTEP diagram of the pre-equilibrium mediate) derived from the bromine interaction with complex of benzene and bromine showing the hexamethylbenzene to emphasize the least-motion...

Arita M, Yoshida M, Hong S, Tjonahen E, GUckman JN, Peta-sis NA, Blumberg RS, Serhan CN. Resolvin El, an endogenous Upid mediator derived from omega-3 eicosapentaenoic acid, protects against 2,4,6-trinitrobenzene sulfonic acid-induced colitis. Proc.Natl.Acad.Sci.U.S.A. 2005 102 7671-676. 

Generation of lipid mediators. Ca -dependent phospholipase activation has been shown to stimulate synthesis of lipid mediators derived from arachidonic acid. The production of these lipid mediators can provoke both short- and long-range effects on bystander cells (e.g. (Bhakdi eta/., 1994 Suttorp efal., 1985 Suttorp eta/., 1992). 

Secondary reactions provoked by pore-forming toxins are very diverse, and are probably responsible for short- and long-range effects in the host organism (for review, see Bhakdi ef al., 1994). Locally, PFTs can counteract the host defense system directly by killing phagocytes and lymphocytes, and they promote spread of infections by their cytocidal action on tissue cells (see e.g. Bhakdi et al., 1994 Paton et al., 1993 Trifillis et al., 1994 Welch, 1991 Welch et al., 1995 Welch et al., 1981). Mediators, derived for example from arachidonic acid, will provoke inflammation. 

EIA enzyme immunoassay. See ELISA, eicosanoids A family of fatty acid mediators derived from arachidonic acid, and which includes prostaglandins, thromboxanes and leukotrienes. 

Prostanoids, consisting of prostaglandins (PGs) and thromboxanes (TXs), are members of the lipid mediators derived enzymatically from fatty acids. Arachidonic acid, a C2o essential fatty acid for most mammalians, is freed from the phospholipid molecule by phospholipase A2, which cleaves off the fatty acid precursor. Prostanoids are produced in a wide variety of cells throughout the body from the sequential oxidation of arachidonic acid by cyclooxygenase, PG hydroperoxidase, and a series of prostaglandin synthases (Figure 2.1). 

Table 3 Biologically Active Mediators Derived from Inflammatory Cells...

Mediators Derived From Non-parendiymal Cells and Cytokines in Hepatotoxicology... 

Leukotrienes (LTs) are lipid mediators derived enzymatically from arachidonic acid. Structurally, these eicosanoids contain a conjugated triene functionality. LTB4 and LTC4 are the two important leukotrienes. Mass spectrometry has played... 

Arita, M., Yoshida, M., Hong, S., Tjonahen, R., Glickman, J.N., Petasis, N.A., Blumberg, R.S., and Serhan, C.N. (2005) Resolvin R1, an endogenous lipid mediator derived from omega-3 eicosa-pentaenoic acid, protects against 2,4,6-trinitrobenzene sulfonic... 

FIGURE 9.2 Biosynthetic pathways and actions of selected lipid mediators derived from ARA, EPA, and DHA. 

Initially, the resolution of acute inflammation was thought to be a passive process, that eventually takes place without the active involvement of particular pathways or mediators. Recent investigations, however, revealed that resolution is an active process mediated by certain molecular mediators that activate pro-resolving biochemical pathways and cellular signaling. Notably, several lipid mediators derived from ARA, EPA, and DHA were shown to play major roles in promoting resolution [1-4]. 

The resolvins are lipid mediators derived from eicosapentaenoic acid (E-resolvins) or docosahexaenoic acid (D-resolvins), which are generated during the resolution phase of inflammation and act to dampen and resolve mflammation. 

The lipid mediators derived from ARA, EPA, and DHA discussed above (i.e., lipox-ins, resolvins, protectins, and maresins) have different biosynthetic origins and variable overall bioactivity profiles. These molecules have been collectively termed specialized pro-resolving lipid mediators (SPM), due to their conunon biological role, namely their ability to reduce the inflanunatory response, and to promote the resolution of inflammation and return to homeostasis. 

Marcon R., Bento A. E, Dutra R. C., Bicca M. A., Leite D. F. R, CaUxto J. B. 2013. Maresin 1, a proresolving Upid mediator derived from omega-3 polynnsaturated fatty acids, exerts protective actions in murine models of colitis. 

More recent applications of the Sonogashira reaction in PUFA synthesis include Spurs and Rodriguez s synthesis of maresin 1 (56) [72], a potent anti-inflammatory lipid mediator derived from DHA (7). As shown in Scheme 3.21, the Sonogashira cross coupling reaction of alkyne 82, bearing an unprotected secondary alcohol, with vinyl iodide 83, provided compound 84. Then, removal of the TES group, Boland reduction of the triple bond, and subsequent hydrolysis of the methyl ester afforded maresin 1 (56). 

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