coenzyme-q10 and linsidomine

We have examined potent peroxynitrite ion (ONOO-) generator 3-morpholinosydnonimine (SIN-1)-induced neurotoxicity in control wild-type (control(wt)) mice, metallothionein double knockout (MT(dko)) mice, metallothionein-transgenic (MT(trans)) mice, and in cultured human dopaminergic (SK-N-SH) neurons to determine the neuroprotective potential of metallothionein against ONOO(-)-induced neurodegeneration in Parkinson disease (PD). SIN-1-induced lipid peroxidation, reactive oxygen species synthesis, caspase-3 activation, and apoptosis were attenuated by metallothionein gene overexpression and augmented by metallothionein gene down-regulation. A progressive nigrostriatal dopaminergic neurodegeneration in weaver mutant (wv/wv) mice was associated with enhanced nitrite ion synthesis, metallothionein down-regulation, and significantly reduced dopamine synthesis and 18F-DOPA uptake as determined by high-resolution micropositron emission tomography neuroimaging. The striatal (18)F-DOPA uptake was significantly higher in MT(trans) mice than in MT(dko) and alpha-synuclein knockout (alpha-Syn(ko)) mice. These observations provide further evidence that nitric oxide synthase activation and ONOO- synthesis may be involved in the etiopathogenesis of PD, and that metallothionein gene induction may provide neuroprotection.

Topics: Animals; Apoptosis; Caspase 3; Caspases; Coenzymes; Dopamine; Enzyme Activation; Lipid Peroxidation; Metallothionein; Mice; Mice, Inbred C57BL; Mice, Transgenic; Molsidomine; Oxidative Stress; Parkinson Disease; Reactive Oxygen Species; Ubiquinone

Coenzyme Q (Q10) and alpha-tocopherol cooperatively delay the onset of diene conjugation in isolated human low density lipoprotein if supplied in water-soluble preparations to blood serum. Both copper ions and morpholino sydnonimine (in the presence of glucose; SIN-1-glucose) -driven diene conjugation is measurable as soon as both reduced Q10 and tocopherol are oxidized, where tocopherol oxidation starts after 80-90% consumption of reduced Q10. LDL-bound Q10 in turn can be rapidly reduced by dihydrolipoic acid (thioctic acid). This reaction is at least 10 times faster than reduction by ascorbic acid.

Topics: Antioxidants; Ascorbic Acid; Coenzymes; Copper; Humans; Ions; Lipoproteins, LDL; Male; Middle Aged; Models, Biological; Molsidomine; Nitric Oxide Donors; Oxygen; Protein Binding; Thioctic Acid; Time Factors; Ubiquinone; Vitamin E