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Nitric Oxide Reduces the Palmitoylation of Rat Myelin Proteolipid Protein by an Indirect Mechanism

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Brain slices from 20-day-old rats were incubated with [3H]palmitate for 2 hours in the absence or presence of the NO-donors S-nitroso-N-acetyl-penicillamine (SNAP), ethyl-2-[hydroxyimino]-5-nitro-3-hexeneamide (NOR-3), 4-phenyl-3-furoxan carbonitrile (PFC) and sodium nitroprusside (SNP). Each of these drugs reduced the incorporation of [3H]palmitate into myelin proteolipid protein (PLP) in a concentration-dependent manner, SNP being the most active. The effect of SNAP was prevented by the NO-scavenger PTIO (2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide). Furthermore, decayed-SNAP, sodium nitrite and N- nitrosopyrrolidine were inactive, suggesting that free NO and/or some of its direct oxidation products are the active molecular species. The amount of fatty acids bound to PLP and the rate of deacylation were unaffected by NO. Although NO diminished the number of thiols in brain and myelin proteins, with the formation of both nitrosothiols and disulfides, these changes did not parallel those in PLP acylation. In contrast, NO was effective at reducing the palmitoylation of brain and myelin lipids, and this effect along with that of PLP, was ascribed to a decrease in palmitoyl-CoA levels. The NO-induced reduction in acyl-CoA concentration was due to the decline in ATP levels, while the amount of [3H]palmitate incorporated into the tissue, the activity of palmitoyl-CoA ligase and palmitoyl-CoA hydrolase, and the concentration of CoASH were unaltered by the drugs. Experiments with endogenously-synthesized [18O]fatty acids confirmed that NO affects predominantly the ATP-dependent palmitoylation of PLP. In conclusion, the inhibitory action of NO on the fatty acylation of PLP is indirect and caused by energy depletion.

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  1. Department of Cell Biology and Physiology, University of New Mexico-Health Sciences Center, Albuquerque, New Mexico, 87131

    Oscar A. Bizzozero, Heather Bixler, Jaipriya Parkhani & Andrjez Pastuszyn

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Bizzozero, O.A., Bixler, H., Parkhani, J. et al. Nitric Oxide Reduces the Palmitoylation of Rat Myelin Proteolipid Protein by an Indirect Mechanism. Neurochem Res 26, 1127–1137 (2001). https://doi.org/10.1023/A:1012370822754

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