Neuronal and retinal tissue are high in phospholipids containingone or two long chain polyunsaturated acyl chains. A further refinement of our analysis of the time-resolved anisotropy decay of the hydrophobic fluorescence probe diphenylhexatriene (DPH) allows a measure of the acyl chain packing order in the membrane interior vs the portion of the chain closer to the interfacial region. Polyunsaturated acyl chains result in the highest degree of acyl chain disorder and produce the highest values of acyl chain packing free volume, a parameter which promotes the greatest degree of formation of the activate conformation of the G protein-coupled receptor, rhodopsin. Cholesterol has been shown to decrease both acyl chain packing free volume and rhodopsin activation. Our studies show that polyunsaturated phospholipids are able to resist the ordering effects of cholesterol and maintain their unique acyl chain packing properties. Recent findings demonstrate that acyl chain packing is increased by increased osmotic stress, due to the dehydration of the phospholipid head group. Ethanol on the other hand has an antagonistic effect of decreasing acyl chain order. These effects are important in understanding in vivo mechanisms of alcohol action since ethanol effects occur in the presence of an osmotic background of plasma. These findings have important implications for integral membrane protein function and suggest that highly unsaturated phospholipids found in retina and neuronal tissue can optimize receptor function, are able to resist the effects of certain compositional variation, such as increases in cholesterol content, and may modulate membrane sensitivity to ethanol. - neurosciences, nutritional disorders

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Intramural Research (Z01)
Project #
1Z01AA000072-08
Application #
6288638
Study Section
Special Emphasis Panel (LMBB)
Project Start
Project End
Budget Start
Budget End
Support Year
8
Fiscal Year
1999
Total Cost
Indirect Cost
Name
National Institute on Alcohol Abuse and Alcoholism
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Lim, June Y; Lui, Camillia K (2016) Longitudinal Associations Between Substance Use and Violence in Adolescence Through Adulthood. J Soc Work Pract Addict 16:72-92
Lui, Camillia K; Chung, Paul J; Ford, Chandra L et al. (2015) Drinking behaviors and life course socioeconomic status during the transition from adolescence to adulthood among Whites and Blacks. J Stud Alcohol Drugs 76:68-79
Lui, Camillia K; Chung, Paul J; Wallace, Steven P et al. (2014) Social status attainment during the transition to adulthood. J Youth Adolesc 43:1134-50
Niu, Shui-Lin; Mitchell, Drake C; Litman, Burton J (2005) Trans fatty acid derived phospholipids show increased membrane cholesterol and reduced receptor activation as compared to their cis analogs. Biochemistry 44:4458-65
Mitchell, Drake C; Niu, Shui-Lin; Litman, Burton J (2003) Enhancement of G protein-coupled signaling by DHA phospholipids. Lipids 38:437-43
Mitchell, Drake C; Niu, Shui-Lin; Litman, Burton J (2003) DHA-rich phospholipids optimize G-Protein-coupled signaling. J Pediatr 143:S80-6
Niu, Shui-Lin; Mitchell, Drake C; Litman, Burton J (2002) Manipulation of cholesterol levels in rod disk membranes by methyl-beta-cyclodextrin: effects on receptor activation. J Biol Chem 277:20139-45
Niu, Shui-Lin; Litman, Burton J (2002) Determination of membrane cholesterol partition coefficient using a lipid vesicle-cyclodextrin binary system: effect of phospholipid acyl chain unsaturation and headgroup composition. Biophys J 83:3408-15
Litman, B J; Niu, S L; Polozova, A et al. (2001) The role of docosahexaenoic acid containing phospholipids in modulating G protein-coupled signaling pathways: visual transduction. J Mol Neurosci 16:237-42; discussion 279-84
Salem Jr, N; Litman, B; Kim, H Y et al. (2001) Mechanisms of action of docosahexaenoic acid in the nervous system. Lipids 36:945-59

Showing the most recent 10 out of 15 publications