Manganese poisoning and the attack of trivalent manganese upon catecholamines.

Human manganese poisoning or manganism results in damage to the substantia nigra of the brain stem, a drop in the level of the inhibitory neurotransmitter dopamine, and symptoms resembling those of Parkinson's disease. Manganic (Mn3+) manganese ions were shown to be readily produced by O-2 in vitro and spontaneously under conditions obtainable in the human brain. Mn3+ as its pyrophosphate complex was shown to rapidly and efficiently carry out four-electron oxidations of dopamine, its precursor dopa (3,4-dihydroxyphenylalanine), and its biosynthetic products epinephrine and norepinephrine. Mn3+-pyrophosphate was shown to specifically attack dihydroxybenzene derivatives, but only those with adjacent hydroxyl groups. Further, the addition of Mn2+-pyrophosphate to a system containing a flux of O2- and dopamine greatly accelerated the oxidation of dopamine. The oxidation of dopamine by Mn3+ neither produced nor required O2, and Mn3+ was far more efficient than Mn2+, Mn4+ (MnO2), O2-, or H2O2 in oxidizing the catecholamines. A higher oxidation state, Mn(OH)3, formed spontaneously in an aqueous Mn(OH)2 precipitate and slowly darkened, presumably being oxidized to MnO2. Like reagent MnO2, it weakly catalyzed dopamine oxidation. However, both MnO2 preparations showed dramatically increased abilities to oxidize dopamine in the presence of pyrophosphate due to enhancement of the spontaneous formation of the Mn3+ complex. These results strongly suggest that the pathology of manganese neurotoxicity is dependent on the ease with which simple Mn3+ complexes are formed under physiological conditions and the efficiency with which they destroy catecholamines.

[1]  R. H. Kenten,et al.  The oxidation of manganese by peroxidase systems. , 1950, The Biochemical journal.

[2]  G. C. Cotzias,et al.  Chronic manganese poisoning , 1967, Neurology.

[3]  A. Barbeau,et al.  Manganese and extrapyramidal disorders (a critical review and tribute to Dr. George C. Cotzias). , 1984, Neurotoxicology.

[4]  X. Breakefield,et al.  Uptake and binding of dopamine and 6-hydroxydopamine in murine neuroblastoma and fibroblast cells. , 1976, Biochemical pharmacology.

[5]  E. Bonilla,et al.  EFFECT OF l‐DOPA ON BRAIN CONCENTRATION OF DOPAMINE AND HOMOVANILLIC ACID IN RATS AFTER CHRONIC MANGANESE CHLORIDE ADMINISTRATION , 1974, Journal of neurochemistry.

[6]  G. Cohen,et al.  The generation of hydrogen peroxide, superoxide radical, and hydroxyl radical by 6-hydroxydopamine, dialuric acid, and related cytotoxic agents. , 1974, The Journal of biological chemistry.

[7]  L. W. Winkler,et al.  Die Bestimmung des im Wasser gelösten Sauerstoffes , 1888 .

[8]  I. Fridovich,et al.  Superoxide dismutase. An enzymic function for erythrocuprein (hemocuprein). , 1969, The Journal of biological chemistry.

[9]  E. Holtzman,et al.  Microperoxisome distribution in the central nervous system of the rat , 1976, Brain Research.

[10]  I. Fridovich,et al.  Manganese, superoxide dismutase, and oxygen tolerance in some lactic acid bacteria , 1981, Journal of bacteriology.

[11]  I. Fridovich,et al.  The scavenging of superoxide radical by manganous complexes: in vitro. , 1982, Archives of biochemistry and biophysics.

[12]  I. Fridovich,et al.  Investigations of the state of the manganese in Lactobacillus plantarum. , 1982, Archives of biochemistry and biophysics.

[13]  C. Mytilineou,et al.  THE BIOCHEMICAL AND PHARMACOLOGICAL PROPERTIES OF 6‐AMINODOPAMINE: SIMILARITY WITH 6‐HYDROXYDOPAMINE , 1973, Journal of neurochemistry.

[14]  Grahame-Smith Dg,et al.  Catecholamine toxicity : a proposal for the molecular pathogenesis of manganese neurotoxicity and Parkinson's disease , 1984 .

[15]  P. Seeman,et al.  Ascorbate injury and EDTA (or manganese) protection of D2-dopamine receptors. , 1982, European journal of pharmacology.

[16]  J. Langston,et al.  Chronic Parkinsonism in humans due to a product of meperidine-analog synthesis. , 1983, Science.

[17]  M. V. Van Woert,et al.  Brain peroxidase and catalase in Parkinson disease. , 1975, Archives of neurology.

[18]  J. Donaldson,et al.  Enhanced autoxidation of dopamine as a possible basis of manganese neurotoxicity. , 1981, Neurotoxicology.

[19]  R. H. Kenten,et al.  The oxidation of manganese by illuminated chloroplast preparations. , 1955, The Biochemical journal.

[20]  F. Archibald,et al.  Manganese: its acquisition by and function in the lactic acid bacteria. , 1986, Critical reviews in microbiology.

[21]  C. Mytilineou,et al.  1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine destroys dopamine neurons in explants of rat embryo mesencephalon. , 1984, Science.

[22]  H. Thoenen,et al.  Model experiments on the molecular mechanism of action of 6-hydroxydopamine. , 1971, Molecular pharmacology.

[23]  D. Graham Oxidative pathways for catecholamines in the genesis of neuromelanin and cytotoxic quinones. , 1978, Molecular pharmacology.

[24]  I. Fridovich,et al.  Manganese and Defenses against Oxygen Toxicity in Lactobacillus plantarum , 1981, Journal of bacteriology.

[25]  L. Rochette,et al.  Dopamine and norepinephrine turnover in various regions of the rat brain after chronic manganese chloride administration. , 1982, Toxicology.

[26]  D. Graham,et al.  Autoxidation versus covalent binding of quinones as the mechanism of toxicity of dopamine, 6-hydroxydopamine, and related compounds toward C1300 neuroblastoma cells in vitro. , 1978, Molecular pharmacology.

[27]  Duncan McGregor,et al.  Manganese neurotoxicity: a model for free radical mediated neurodegeneration? , 1982, Canadian journal of physiology and pharmacology.

[28]  P. McCay,et al.  Evidence that peroxidation of lysosomal membranes is initiated by hydroxyl free radicals produced during flavin enzyme activity. , 1973, The Journal of biological chemistry.

[29]  B. Halliwell Manganese ions, oxidation reactions and the superoxide radical. , 1984, Neurotoxicology.

[30]  K. Jellinger,et al.  Brain dopamine and the syndromes of Parkinson and Huntington. Clinical, morphological and neurochemical correlations. , 1973, Journal of the neurological sciences.