Brain mitochondria

Augustin, W. et al.. Beta-carotene cleavage products induce oxidative stress by impairing mitochondrial functions brain mitochondria are more sensitive than liver mitochondria, Free Rad. Biol. Med., 33, S326, 2002. 

Classic antioxidants, vitamin E, vitamin C, and others can suppress the activation of apoptosis. For example, ascorbic acid prevented cytochrome c release and caspase activation in human leukemia cells exposed to hydrogen peroxide [128], Pretreatment with A -acctylcystcinc, ascorbate, and vitamin E decreased homocysteine thiolactone-induced apoptosis in human promyelocytic leukemia HL-60 cells [129]. Resveratrol protected rat brain mitochondria from anoxia-reoxygenation damage by the inhibition of cytochrome c release and the reduction of superoxide production [130]. However, it should be mentioned that the proapoptotic effect of ascorbate, gallic acid, or epigallocatechin gallate has been shown in the same human promyelocytic leukemia cells [131]. 

Patel, M. S. The effect of ketone bodies on pyruvate car-boxylation by rat brain mitochondria. /. Neurochem. 23, 865-867, 1974. 

No CYPlAl protein or activity in purified rat brain mitochondria (Morse et al., 1998). 

Several explanations centre on the enzyme glutamate dehydrogenase, which is assumed to catalyse a nearequilibrium reaction in brain mitochondria ... 

Potent metabolic inhibitors of the citric acid cycle. Fluo-roacetate (F-CH2COO ) must first be converted to flu-oroacetyl-S-CoA (by acetyl-CoA synthetase) and thence to fluorocitrate (by citrate synthase) before it can act as a potent metabohc inhibitor of the aconitase reaction as well as citrate transport. Submicromolar concentrations of ( )-erythro-Q iOTOcitTate can irreversibly inhibit citrate uptake by isolated brain mitochondria. 

Fig. 1. Influence of substituents in the aromatic ring on the selectivity of 3-(2-aminoethoxy)-1,2-benzisoxazole derivatives as monoamine oxidases (MAO) A or B inhibitors. Ratio of selectivity was calculated from IC50 values of MAO A and B determined by an in vitro assay of mouse brain mitochondria using 5-hydroxy tryptamine (5-HT) and 2-phenylethylamine (PEA) as specific substrates, respectively (see Ref. [9]). Smaller values indicate that inhibitors are MAO A selective [71].

Cytochrome C oxidase inhibition. Smoke extract, in the mouse brain mitochondria culture in the presence or absence of vitamin C for 60 minutes, inhibited mitochon-... 

Mitochondrial ATPase inhibition. Smoke extract, in the mouse brain mitochondria culture in the presence or absence of vitamin C for 60 minutes, inhibited mitochondrial ATPase and cytochrome C oxidase activities in a dose-dependent manner. The effect of extract on mitochondria swelling response to calcium stimulation was dependent on calcium concentrations. The extract treatment induced mitochondrial inner membrane damage and vacuolization of the matrix, whereas the outer mitochondrial membrane was preserved. Nicotine produced no significant damage . Mitogenic activity. Water extract of the dried leaf, administered to mice at a concentration of 0.05%, was active on lymphocytes from mesenteric lymph node and lymphocytes B and T. Intracellular Ca level was unchanged. The extract was active on... 

NT007 Yang, Y. M., and G. T. Liu. Injury of mouse brain mitochondria induced by cigarette smoke extract and effect of vitamin C on it in vitro. Biomed Environ Sci 2003 16(3) 256-266. 

Parker M. A., Bazan H. E. R, Marcheselli V., Rodriguez de Turco E. B., and BazanN. G. (2002). Platelet-activating factor induces permeability transition and cytochrome c release in isolated brain mitochondria. J. Neurosci. Res. 69 39-50. 

Carafoli, E., Santella, L., Branca, D., and Brini, M., 2001, Generation, control, and processing of cellular calcium signals, Crit. Rev. Biochem. Mol. Biol. 36, pp. 107-260 Chalmers, S. and Nicholls, D. G., 2003, The Relationship between Free and Total Calcium Concentrations in the Matrix of Liver and Brain Mitochondria, J. Biol. Chem. 278, p. 19062 Colell, A., Garcia-Ruiz, C., Mari, M., and Fernandez-Checa, J. C., 2004, Mitochondrial permeability transition induced by reactive oxygen species is independent of cholesterol-regulated membrane fluidity, FEBS Lett 560, pp. 63-68... 

Nicklas WJ, Vyas I, Heikkila RE (1985) Inhibition of NADH-linked oxidation in brain mitochondria by l-methyl-4-phenyl-pyridine, a metabolite of the neurotoxin, l-methyl-4-phenyl-l,2,5,6-tetrahydropyridine. Life Sd 36 2503-2508. 

The same argument may be used for the brain and CNS. Plasma and mitochondrial membrane bilayers in the CNS in mammals are notably rich in long-chain polyunsaturated FAs, so one might expect brain mitochondria to be more leaky with unusually low P/O ratios. This probably does not occur in vivo because the CNS normally displays very high metabolic rates (under BMR conditions in humans, brain metabolic rates are in the range of 3 /zmol 02... 

The mitochondrial Mg2+ ATPase activity from liver and brain was inhibited by about 50-60% after an administration of 100 mg Al kg 1 body weight in the diet for a period of 90-120 days. By contrast, in the heart mitochondria, the ATPase activity increased from 73 to 212% after this treatment [38]. In this work, it was also found that ADP phosphorylation rates were decreased by 46% and that the changes in the ATPase activity, in general, were paralleled to those of the respiratory rates. The author suggested that these results imply that the effects of Al3+ treatment on respiratory activity and the ATPase activity go hand in hand. Curiously, liver and brain mitochondria presented doubled aluminum concentration and impaired respiration rate, whereas the heart mitochondria, that accumulated 11 times higher amount of aluminum, presented stimulation of respiration. Thus, an indirect action of aluminum in this tissue could be suggested. 

Figure 9.79 Chromatograms of (A) standard succinyl-CoA, obtained by injecting 0.6 nmol of standard solution (retention time for succinyl-CoA peak, 16.3 min), (B) blank, and (C) sample (20 /xL of brain mitochondria containing 0.068 mg of protein). Arrow in the blank points to the retention time of succinyl-CoA. (From Shylaja et al., 1990.)...

Corsi, A., Granata, A.L. (1967). Differential toxicity of fluoroacetate to heart, kidney and brain mitochondria of the living rat. Biochem. Pharmacol. 16 1083-9. 

TJloe, S-.A., Manlan, A.A. and O Neill J.J. 1972 Calcium Efflux and Respiratory Inhibition In Brain Mitochondria. BBRC 48 212-a8. 

Alikhani N, Guo L, Yan S, Kehoe PG, Love S (2011) Decreased proteolytic activity of the mitochondrial amyloid-p degrading enzyme, prep peptidasome, in Alzheimer s disease brain mitochondria. J Alzheimers Dis 27 75-87... 

Zhao, A. Leung, L.Y. Trevor, A. and Castagnoli, N., Jr. C-Formylation in the presence of rat brain mitochondria of the 2,3,4,5-tetrahydro-pyridinium metabolite derived from the psychotomimetic drug phencyclidine. ChemRes Toxicol 4 426-429, 1991. 

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