Brain lipid mediators

The brain has a number of characteristics that make it especially susceptible to free- radical-mediated injury. Brain lipids are highly enriched in polyunsaturated fatty acids and many regions of the brain, for example, the substantia nigra and the striatum, have high concentrations of iron. Both these factors increase the susceptibility of brain cell membranes to lipid peroxidation. Because the brain is critically dependent on aerobic metabolism, mitochondrial respiratory activity is higher than in many other tissues, increasing the risk of free radical Teak from mitochondria conversely, free radical damage to mitochondria in brain may be tolerated relatively poorly because of this dependence on aerobic metabolism. 

Similarly, apolipoprotein E expression increases in neurotoxicity mediated by KA (Table 6.3) (Boschert et al., 1999). Apolipoprotein E is a major lipoprotein in the brain. It is involved in the transport, distribution, and other aspects of cholesterol homeostasis. Apolipoprotein E also plays a dominant role in the mobilization and redistribution of brain lipids in repair, growth, and maintenance of nerve cells (Mahley, 1988). The secretion of apolipoproteins E and D may be differentially regulated in cultured astrocytes. In cell culture systems this depends upon the extracellular lipid milieu (Patel et al., 1995). During neurotoxicity mediated by KA, apolipoprotein E levels increase moderately in astrocytes and apolipoprotein E mRNA increases very strongly in clusters of CA1 and CA3 pyramidal neurons. Based on hybridization in situ and immunohistochemical studies, expression of apolipoprotein E in neurons may be a part of a rescue program to counteract neurodegeneration mediated by KA (Boschert et al., 1999). 

Farooqui A. A. and Florrocks L. A. (2006a). Phospholipase A2-generated lipid mediators in the brain the good, the bad, and the ugly. Neuroscientist 12 245-260. 

Rapoport S. I. (2005). In vivo approaches and rationale for quantifying kinetics and imaging brain lipid metabolic pathways. Prostaglandins Other Lipid Mediat. 77 185-196. 

Fig. 11 Data from metabolomics PMI experiments, (a) Enrichment of retinoic acid by CRABP-GST from a mixture of brain lipids ( P < 0.01, n = 3 1, Student s t-test). (b) StarD3-mediated enrichment of cholesterol from a brain lipid extract...

Thom, S.R. 1990. Carbon monoxide-mediated brain lipid peroxidation in the rat. J. Appl. Physiol. 68 (3) 997—1003. 

Chylomicron remnants and very low density lipoprotein (VLDL) remnants are rapidly removed from the circulation by receptor-mediated endocytosis. ApoE, the major apolipoprotein of the chylomicron in the brain, binds to a specific receptor and is essential for the normal catabolism of triglyceride-rich lipoprotein constituents. Defects in apolipoprotein E result in familial dysbetalipoproteinemia, or type III hyperlipoproteinemia (HLP III), in which increased plasma cholesterol and triglycerides are the consequence of impaired clearance of chylomicron and VLDL remnants (Mahley et al., 1999). In the brain, lipidated apoE binds aggregated in a isoform-speciflc manner, apoE4 being much more effective than the other forms,... 

Cornford EM, Braun LD, Oldendorf WH, Hill MA (1982) Comparison of lipid-mediated blood-brain-barrier penetrabihty in neonates and adults. Am J Physiol 243 C161-C168. 

Kaech S, Kim JB, Canola M, Ralston E (1996) Improved lipid-mediated gene transfer into primary cultures of hippocampal neurons. Brain Res Mol Brain Res 35 344-348. 

Thom, Sr. Antagonism of carbon monoxide-mediated brain lipid peroxidation by hyperbaric oxygen. ToxicolApplPharmacol 1990 105(2) 340-44. 

Elsu, C. Y., Lui, T. H., Xu, J., Hogan, E. L., and Chao, J., Lipid inflammatory mediators in ischemic brain edema and injury, in Lipid Mediators in Ischemic Brain Damage and Experimental Epilepsy, Bazen, N. G., Ed., S. Karger, Basel, 1990, 85. 

Hassani, Z. et al. (2004). Lipid-mediated siRNA delivery down-regulates exogenous gene expression in the mouse brain at picomolar levels. J Gene Med. 7, 198-207. 

DHA is very abundant in excitable membranes in the retina and brain, particularly in PL of the rod outer segment of retina and of synaptic vesicles, and is important in vision. However, the mechanism by which DHA functions in retina is not well understood. Chen et al. (Y. Chen, 1993) suggest that DHA in retina might be involved in shuttling 11-c/j-retinal to photoreceptors, whereas Niu et al. (S. Niu, 2004) propose that DHA in PL increases the efficiency of G-protein-mediated signal transduction of rhodopsin. In humans, supplementation of infant formula with DHA accelerates the development of visual functions in pre-term infants. The novel protective lipid mediator docosanoids, namely, Protectin D1 (C. Serhan, 2002) and 17S-hydroperoxy-DHA (V. Marcheselli, 2003), have been suggested to mediate the beneficial effects of DHA. 

Goto, K. Kondo, H. Heterogeneity of diacylglycerol kinase in terms of molecular structure, biochemical characteristics and gene expression localization in the brain. J. Lipid Mediat. Cell Signal, 14, 251-257 (1996)... 

Apolipoprotein E (apoE) is an important lipid transport protein in human plasma and brain. It mediates hepatic clearance of remnant lipoproteins as a high-affin-ity ligand for the low-density lipoprotein receptor (LDLR) family, including LDLR, LDLR-related protein (LRP), and cell surface heparan sulfate PGs (71). In the liver, heparan sulfate PGs facilitate the interaction of remnant particles with LRP, which is known as the heparan sulfate PG-LRP pathway, in which apoE initially interacts... 

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