Modulation of endogenous ADP-ribosylation in rat brain.
Endogenous ADP-ribosylation of proteins was measured in homogenates, membranes, and cytosol from rat brain regions. Several proteins were ADP-ribosylated in homogenates, especially a 49 kDa protein. Sodium nitroprusside, a source of nitric oxide, particularly enhanced the ADP-ribosylation of 47 kDa and 39 kDa proteins. Levels of basal and sodium nitroprusside-stimulated ADP-ribosylated proteins were similar, but not identical, in homogenates from the cerebral cortex, hippocampus, striatum, thalamus and cerebellum. In neonatal cerebral cortex, ADP-ribosylation of an additional 110 kDa protein was detected and this was also enhanced by sodium nitroprusside. ADP-ribosylation of the 110 kDa protein was evident one and two days after birth, but not at five days and later. Each protein demonstrated unique sensitivities to sodium nitroprusside and rates of ADP-ribosylation. Cyclic GMP did not mimic the effects of sodium nitroprusside. Mg2+ inhibited ADP-ribosylation of the 49 kDa and 47 kDa proteins but had a smaller effect on the 39 kDa protein. ADP-ribosylation in the cytosol predominantly affected only a single protein of 39 kDa, and this was stimulated by sodium nitroprusside and by addition of cofactors necessary for activation of nitric oxide synthase. Several proteins in membranes were ADP-ribosylated and the 49 and 47 kDa proteins were released from the membranes coincidentally with ADP-ribosylation. The predominate substrates of endogenous ADP-ribosylation did not appear to be substrates for pertussis toxin-induced ADP-ribosylation. These and previously published results indicate that nitric oxide generated from sodium nitroprusside or endogenous sources may have modulatory effects through regulation of the endogenous ADP-ribosylation of proteins.
Williams
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MB
Department of Psychiatry and Behavioral Neurobiology, University of Alabama, Birmingham 35294.
Li
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Gu
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Jope
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D000246:Adenosine Diphosphate Ribose / Q000378:metabolism*; D000375:Aging / Q000378:metabolism; D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000378:metabolism*; D002855:Chromatography, Thin Layer; D008274:Magnesium / Q000494:pharmacology; D008297:Male; D008627:Mercuric Chloride / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009599:Nitroprusside / Q000494:pharmacology; D009994:Osmolar Concentration; D010727:Phosphoric Diester Hydrolases / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014018:Tissue Distribution
D009419:Nerve Tissue Proteins; D009599:Nitroprusside; D000246:Adenosine Diphosphate Ribose; D008627:Mercuric Chloride; D010727:Phosphoric Diester Hydrolases; D008274:Magnesium