ISSN:
1573-6903
Keywords:
Dopamine
;
striatum
;
synaptosomes
;
iron
;
peroxidation
;
membrane-viscosity
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract Crude striatum synaptosomes (P2 fraction) from Fisher 344 female rats were incubated in the presence of ADP-chelated Fe3+ (0.5–50 μM) and ascorbate (250 μM). Intrasynaptosomal conversion of tyrosine to dopamine (DA) was measured by14CO2 evolution froml-[1-14C]tyrosine in the absence of added cofactors and DOPA decarboxylase. Malondialdehyde (MDA) was measured as an index of lipid peroxidation. A concentration-dependent inhibition of DA synthesis by ADP-Fe3+/ascorbate was found with 50% inhibition occurring at 2.5 μM Fe3+ concentration. This was accompanied by marked accumulation of MDA. Ascorbate or ADP alone did not affect DA synthesis and ADP-Fe3+ in the absence of exogenous ascorbate was effective only above 25 μM. Exogenously added MDA did not inhibit DA synthesis. Purified synaptosomes were isolated from peroxidized and control P2 fractions using sucrose gradients. Membrane microviscosity of the purifled synaptosomes was assessed by nitroxyl spin labels of stearic acid using electron paramagetic resonance techniques. There was a significant increase in membrane microviscosity as a result of ADP-Fe3+/ascorbate induced peroxidation. Maleimide nitroxide spin-label binding to protein sulhydryls was significantly modified by peroxidation of striatum synaptosomes. The weakly immobilized component of the sulhydryl spin-label (w) was drastically decreased whereas the strongly immobilized component (s) was modified less, thus leading to a marked reduction of w/s ratio. The exposure of striatum synaptosomes to the peroxidizing system resulted in a significant increase in total iron and in a 25% decrease in protein sulhydryl content. It is concluded that ironinduced damage to the DA synthetic system is mediated by alterations of the structural properties of nerve ending membranes.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00964867
Permalink
