Iron interactions and other biological reactions mediating the physiological and toxic actions of manganese

Biochemical Pharmacology

Volumn 66, Issue 1, 2003, Pages 1-13

  Roth, Jerome A ^a   Garrick, Michael D ^a  

^a UNIVERSITY AT BUFFALO   (United States)

Author keywords

Cell death; Divalent metal transporter 1; Iron; Manganese; Manganism; Metal transport

Indexed keywords

FERROUS ION; HEAVY METAL; IRON; MANGANESE; NATURAL RESISTANCE ASSOCIATED MACROPHAGE PROTEIN 2; TRANSFERRIN;

APOPTOSIS; BLOOD BRAIN BARRIER; CELL TRANSPORT; CHEMICAL INDUSTRY; CHEMICAL INTERACTION; CYTOTOXICITY; DIETARY INTAKE; HEALTH HAZARD; HEAVY METAL POISONING; HOMEOSTASIS; HUMAN; IRON INTAKE; IRON STORAGE; LONG TERM EXPOSURE; LUNG FUNCTION; MANGANESE DEFICIENCY; MANGANISM; MINER; NERVE CELL NECROSIS; NEUROTOXICITY; NONHUMAN; OXIDATIVE STRESS; PARKINSON DISEASE; PRIORITY JOURNAL; PROTEIN BINDING; REGULATORY MECHANISM; REVIEW; WELDING;

EID: 0038683166     PISSN: 00062952     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0006-2952(03)00145-X     Document Type: Review

References (159)

1. International Manganese Institute brochure. Paris, France; 2001.
2. Molders N., Schilling P.J., Wong J., Roos J.W., Smith I.L. X-ray fluorescence mapping and micro-XANES spectroscopic characterization of exhaust particulates emitted from auto engines burning MMT-added gasoline. Environ. Sci. Technol. 35:2001;3122-3129.
3. Kemmerer A.R., Elvehjem C.A., Hart E.B. Studies on the relation of manganese to the nutrition of the mouse. J. Biol. Chem. 92:1931;623-630.
4. Orent E.R., McCollum E.V. Effects of deprivation of manganese in the rat. J. Biol. Chem. 92:1931;651-678.
5. Schroeder H.A., Balassa J.J., Tipton I.H. Essential trace metals in man: manganese. A study in homeostasis. J. Chronic. Dis. 19:1966;545-571.
6. Hurley L.S. Teratogenic aspects of manganese, zinc, and copper nutrition. Physiol. Rev. 61:1981;249-295.
7. Keen C.L., Ensunsa J.L., Watson M.H., Baly D.L., Donavan S.M., Monaco M.H., Clegg M.S. Nutritional aspects of manganese from experimental studies. Neurotoxicology. 20:1999;213-223.
8. Grieger J.L. Nutrition versus toxicology of manganese in humans: evaluation of potential markers. Neurotoxicology. 20:1999;205-212.
9. Chan A.W.K., Minski M.J., Lim L., Lai J.C.K. Changes in brain regional manganese and magnesium levels during postnatal development: modulation by chronic manganese administration. Metab. Brain Dis. 7:1992;21-33.
10. Keen CL, Zidenberg-Cherr S. Manganese. In: Zigler EE, Filer LJ, editors. Present knowledge in nutrition. 7th ed. Washington, DC: ILSI Press; 1996. p. 334-43.
11. Nowak T., Suelter C. Pyruvate kinase: activation by and catalytic role of the monovalent and divalent cations. Mol. Cell. Biochem. 35:1982;65-75.
12. Singh T.J. Activation of a manganese-dependent membrane protein kinase by serine and tyrosine phosphorylation. Biochem. Biophys. Res. Commun. 171:1990;75-83.
13. 2+-dependent enzyme impairs its regulation by inhibitor 1. Biochemistry. 36:1997;6986-6992.
14. 2+-independent one. FEBS Lett. 447:1999;29-33.
15. Takeuchi M., Ishida A., Kameshita I., Kitani T., Okuno S., Fujisawa H. Identification and characterization of CaMKP-N, nuclear calmodulin-dependent protein kinase phosphatase. J. Biochem. (Tokyo). 130:2001;833-840.
16. Tian G., Kane L.S., Holmes W.D., Davis S.T. Modulation of cyclin-dependent kinase 4 by binding of magnesium(II) and manganese(II). Biophys. Chem. 95:2002;79-90.
17. Wedler F.C., Denman R.B., Roby W.G. Glutamine synthetase from ovine brain is a manganese(II) enzyme. Biochemistry. 21:1982;6389-6396.
18. Wedler F.C., Denman R.B. Glutamine synthetase: the major Mn(II) enzyme in mammalian brain. Curr. Top. Cell Regul. 24:1984;153-169.
19. Zhang P., Anglade P., Hirsch E.C., Javoy-Agid F., Agid Y. Distribution of manganese-dependent superoxide dismutase in the human brain. Neuroscience. 6:1994;317-330.
20. Powell J.T., Brew K. Metal ion activation of galactosyltransferase. J. Biol. Chem. 251:1976;3645-3652.
21. Kuhn N.J., Ward S., Leong W.S. Submicromolar manganese dependence of Golgi vesicular galactosyltransferase (lactose synthetase). Eur. J. Biochem. 195:1991;243-250.
22. Yang P., Klimis-Tavantzis D.J. Effects of dietary manganese on arterial glycosaminoglycan metabolism in Sprague-Dawley rats. Biol. Trace Elem. Res. 64:1998;275-288.
23. Rens-Domiano S., Roth J.A. Characterization of tyrosylprotein sulfotransferase from rat liver and other tissues. J. Biol. Chem. 264:1989;899-905.
24. Kitahara N., Sawai Y., Tsukada K. Purification and properties of magnesium- and manganese-dependent ribonucleases H from chick embryo. J. Biochem. Tokyo. 92:1982;855-864.
25. 2+-dependent 5′-nucleotidase activity in isolated rod outer segments. Exp. Eye Res. 45:1987;813-821.
26. Song J.K., Hunt J.A. Specific role of manganese and magnesium on RNA synthesis in rabbit bone marrow erythroid cell nuclei. Biol. Trace Elem. Res. 16:1988;203-219.
27. Bolton E.C., Mildvan A.S., Boeke J.D. Inhibition of reverse transcription in vivo by elevated manganese ion concentration. Mol. Cell. 9:2002;879-889.
28. 2+ ion suggests how its characteristic motifs are involved in exonuclease activity. Proc. Natl. Acad. Sci. U.S.A. 99:2002;5908-5912.
29. Butterworth J., Priestman D. Substrate specificity of manganese-activated prolidase in control and prolidase-deficient cultured skin fibroblasts. J. Inherit. Metab. Dis. 7:1984;32-34.
30. Lenney J.F. Separation and characterization of two carnosine-splitting cytosolic dipeptidases from hog kidney (carnosinase and non-specific dipeptidase). Biol. Chem. Hoppe Seyler. 371:1990;433-440.
31. Ash D.E., Cox J.D., Christianson D.W. Arginase: a binuclear manganese metalloenzyme. Met. Ions Biol. Syst. 37:2000;407-428.
32. Reed G.H., Scrutton M.C. Pyruvate carboxylase from chicken liver. Magnetic resonance studies of the effect of substrates and inhibitors on the environment of the bound manganese. J. Biol. Chem. 249:1974;6156-6162.
33. Baly D.L., Keen C.L., Hurley L.S. Pyruvate carboxylase and phosphoenolpyruvate carboxykinase activity in developing rats: effect of manganese deficiency. J. Nutr. 115:1985;872-879.
34. 2+ substrate complexes. J. Biol. Chem. 257:1982;5515-5522.
35. 2+ in the regulation of cytosolic phosphoenolpyruvate carboxykinase from rat liver is unlikely. Biochem. J. 292:1993;365-370.
36. 3)-ligand interaction, identification of a heterodimeric RGD binding site on the vitronectin receptor. J. Biol. Chem. 265:1990;2168-2172.
37. Hemler M.E. VLA proteins in the integrin family: structure, functions, and their role on leukocytes. Annu. Rev. Immunol. 8:1990;365-400.
38. Reichardt L.F., Tomaselli K.J. Extracellular matrix molecules and their receptors: functions in neural development. Annu. Rev. Neurosci. 14:1991;531-570.
39. Humphries M.J. Integrin activation: the link between ligand binding and signal transduction. Curr. Opin. Cell Biol. 8:1996;632-640.
40. Gailit J., Ruoslahti E. Regulation of the fibronectin receptor affinity by divalent cations. J. Biol. Chem. 263:1988;12927-12932.
41. Yanai T., Shimo-Oka T., Ii I. Manganese ion elicits a binding activity of placenta vitronectin receptors to fibronectin cell-binding domain. Cell Struct. Funct. 16:1991;149-156.
42. Elices M.J., Urry L.A., Hemler M.E. Receptor functions for the integrin VLA-3: fibronectin, collagen, and laminin binding are differentially influenced by ARG-GLY-ASP peptide and by divalent cations. J. Cell Biol. 112:1991;169-181.
43. Turner D.C., Flier L.A., Carbonetto S. Magnesium-dependent attachment and neurite outgrowth by PC12 cells on collagen and laminin substrata. Dev. Biol. 121:1987;510-525.
44. Lin W.H., Higgins D., Marcucci K.A., Pacheco M., Aletta J.M., Roth J.A. Manganese induces spreading and process outgrowth in rat pheochromocytoma cells. J. Neurosci. Res. 34:1993;546-561.
45. V integrins. Brain Res. 885:2000;220-230.
46. Walowitz J., Roth J.A. Activation of ERK1 and ERK2 is required for manganese-induced neurite outgrowth in rat pheochromocytoma (PC12) cells. J. Neurosci. Res. 57:1999;847-854.
47. Roth J.A., Walowitz J., Browne R.W. Manganese-induced rat pheochromocytoma (PC12) cell death is independent of caspase activation. J. Neurosci. Res. 61:2000;162-171.
48. Kantlehner M., Schaffner P., Finsinger D., Meyer J., Jonczyk A., Diefenbach B., Nies B., Holzemann G., Goodman S.L., Kessler H. Surface coating with cyclic RGD peptides stimulates osteoblast adhesion and proliferation as well as bone formation. Chembiochem. 1:2000;107-114.
49. Duong L.T., Lakkakorpi P., Nakamura I., Rodan G.A. Integrins and signaling in osteoclast function. Matrix Biol. 19:2000;97-105.
50. Sigurdson S.L., Lwebuga-Mukasa J.S. Divalent cation-dependent regulation of rat alveolar epithelial cell adhesion and spreading. Exp. Cell Res. 1:1994;71-79.
51. 2+-enhanced, RGD-dependent adhesion technique for isolation of adult rat type II alveolar epithelial cells for immediate functional studies. Am. J. Respir. Cell Mol. Biol. 10:1994;347-354.
52. Ruoslahti E. Integrin signaling and matrix assembly. Tumour Biol. 17:1996;117-124.
53. Clegg M.S., Donovan S.M., Monaco M.H., Baly D.L., Ensunsa J.L., Keen C.L. The influence of manganese deficiency on serum IGF-1 and IGF binding proteins in the male rat. Proc. Soc. Exp. Biol. Med. 219:1998;41-47.
54. Strause L.G. Teratogenic aspects of manganese, zinc, and copper nutrition. Physiol. Rev. 61:1981;249-295.
55. Strause L.G., Hegenauer J., Saltman P., Cone R., Resnick D. Effects of long-term dietary manganese and copper deficiency on rat skeleton. J. Nutr. 116:1986;135-141.
56. Chan D.W., Son S.-C., Block W., Ye R., Khanna K.K., Wold M.S., Douglas P., Goodarzi A.A., Pelley J., Taya Y., Lavin M.F., Lees-Miller S.P. Purification and characterization of ATM from human placenta. J. Biol. Chem. 275:2000;7803-7810.
57. Reginster J.Y., Strause L.G., Saltman P., Franchimont P. Trace elements and postmenopausal osteoporosis: a preliminary study of decreased serum manganese. Med. Sci. Res. 16:1988;337-338.
58. Saltman P.D., Strause L.G. The role of trace minerals in osteoporosis. J. Am. Coll. Nutr. 12:1993;384-389.
59. Rico H., Gómez-Raso N., Revilla M., Hernández E.R., Seco C., Páez E., Crespo E. Effects on bone loss of manganese alone or with copper supplement in ovariectomized rats. A morphometric and densitomeric study. Eur. J. Obstet. Gynecol. Reprod. Biol. 90:2000;97-101.
60. Svensson O., Engfeldt B., Reinholt B., Hjerpe A. Manganese rickets: a biochemical stereologic study with special reference to the effect of phosphate. Clin. Orthop. 218:1987;302-311.
61. Carl G.F., Blackwell L.K., Barnett F.C., Thompson L.A., Rissinger C.J., Olin K.L., Critchfield J.W., Keen C.L., Gallagher B.B. Manganese and epilepsy: brain glutamine synthetase and liver arginase activities in genetically epilepsy prone and chronically seizured rats. Epilepsia. 34:1993;441-446.
62. Carl G.F., Keen C.L., Gallagher B.B., Clegg M.S., Littleton W.H., Flannery D.B., Hurley L.S. Association of low blood manganese concentrations with epilepsy. Neurology. 36:1986;1584-1587.
63. Ekmekcioglu C., Prohaska C., Pomazal K., Steffan I., Schernthaner G., Marktl W. Concentrations of seven trace elements in different hematological matrices in patients with type 2 diabetes as compared to healthy controls. Biol. Trace Elem. Res. 79:2001;205-219.
64. Huang C.C., Lu C.S., Chu N.S., Hochberg F., Lilienfeld D., Olanow W., Calne D.B. Progress after chronic manganese exposure. Neurology. 43:1993;1479-1483.
65. Olanow C.W., Good P.F., Shinotoh H., Hewitt K.A., Vingerhoets F., Snow B.J., Beal M.F., Calne D.B., Perl D.P. Manganese intoxication in the rhesus monkey: a clinical imaging pathologic and biochemical study. Neurology. 46:1996;492-498.
66. Mergler D., Baldwin M. Early manifestations of manganese neurotoxicity in humans: an update. Environ. Res. 73:1997;92-100.
67. Pal P.K., Samii A., Calne D.B. Manganese neurotoxicity: a review of clinical features imaging and pathology. Neurotoxicology. 20:1999;227-238.
68. Gorell J.M., Johnson C.C., Rybicki B.A., Peterson E.L., Kortsha G.X., Brown G.G., Richardson R.J. Occupational exposure to manganese, copper, lead iron, mercury and zinc and the risk of Parkinson's disease. Neurotoxicology. 20:1999;239-248.
69. Hudnell H.K. Effects from environmental Mn exposures: a review of the evidence from non-occupational exposure studies. Neurotoxicology. 20:1999;379-397.
70. Tomás-Camardiel M., Herrera A.J., Venero J.L., Sánchez-Hidalgo M.C., Cano J., Machado A. Differential regulation of glutamic acid decarboxylase mRNA and tyrosine hydroxylase mRNA expression in the aged manganese-treated rats. Brain Res. Mol. Brain Res. 103:2002;116-129.
71. Kita H., Tokuno H., Nambu A. Monkey globus pallidus external segment neurons projecting to the neostriatum. Neuroreport. 10:1999;1467-1472.
72. Kim Y., Kim J.M., Kim J.W., Yoo C.I., Lee C.R., Lee J.H., Kim H.K., Yang S.O., Chung H.K., Lee D.S., Jeon B. Dopamine transporter density is decreased in Parkinsonian patients with a history of manganese exposure: what does it mean? Mov. Disord. 17:2002;568-575.
73. Hauser R.A., Zesiewicz T.A., Rosemurgy A.S., Martinez C., Olanow C.W. Manganese intoxication and chronic liver failure. Ann. Neurol. 36:1994;871-875.
74. Krieger D., Krieger S., Jansen O., Gass P., Theilmann L., Lichtnecker H. Manganese and chronic hepatic encephalopathy. Lancet. 346:1995;270-274.
75. Spahr L., Butterworth R.F., Fontaine S., Bui L., Therrien G., Milette P.C., Lebrun L.H., Zayed J., Leblanc A., Pomier-Layrargues G. Increased blood manganese in cirrhotic patients: relationship to pallidal magnetic resonance signal hyperintensity and neurological symptoms. Hepatology. 24:1996;1116-1120.
76. Hauser R.A., Zesiewicz T.A., Martinez C., Rosemurgy A.S., Olanow C.W. Blood manganese correlates with brain magnetic resonance imaging changes in patients with liver disease. Can. J. Neurol. Sci. 23:1996;95-98.
77. Sassine M.P., Mergler D., Bowler R., Hudnell H.K. Manganese accentuates adverse mental health effects associated with alcohol use disorders. Biol. Psychiatry. 51:2002;909-921.
78. Papavasiliou P.S., Miller S.T., Cotzias G.C. Role of liver in regulating distribution and excretion of manganese. Am. J. Physiol. 211:1966;211-216.
79. Hay J.E. Bone disease in cholestatic liver disease. Gastroenterology. 108:1995;276-283.
80. Sinigaglia L., Fargion S., Fracanzani A.L., Binelli L., Battafarano N., Varenna M., Piperno A., Fiorelli G. Bone and joint involvement in genetic hemochromatosis: role of cirrhosis and iron overload. J. Rheumatol. 24:1997;1809-1813.
81. Monegal A., Navasa M., Guanabens N., Peris P., Pons F., Martinez de Osaba M.J., Rimola A., Rodes J., Munoz-Gomez J. Osteoporosis and bone mineral metabolism disorders in cirrhotic patients referred for orthotopic liver transplantation. Calcif. Tissue Int. 60:1997;148-154.
82. Roth J.A., Horbinski C., Higgins D., Lein P., Garrick M.D. Mechanisms of manganese-induced rat pheochromocytoma (PC12) cell death and cell differentiation. Neurotoxicology. 23:2002;147-157.
83. Sziraki I., Rauhala P., Chiueh C.C. Novel protective effect of manganese against ferrous citrate-induced lipid peroxidation and nigrostriatal neurodegeneration in vivo. Brain Res. 698:1995;285-287.
84. Sziraki I., Mohanakumar K.P., Rauhala P., Kim H.G., Yeh K.J., Chiueh C.C. Manganese: a transition metal protects nigrostriatal neurons from oxidative stress in the iron-induced animal model of parkinsonism. Neuroscience. 85:1998;1101-1111.
85. Sziraki I., Rauhala P., Koh K.K., van Bergen P., Chiueh C.C. Implications for atypical antioxidative properties of manganese in iron-induced brain lipid peroxidation and copper-dependent low density lipoprotein conjugation. Neurotoxicology. 20:1999;455-466.
86. Talavera E.J., Arcaya J.L., Giraldoth D., Suarez J., Bonilla E. Decrease in spontaneous motor activity and in brain lipid peroxidation in manganese and melatonin treated mice. Neurochem. Res. 24:1999;705-708.
87. Sloot W.N., van der Sluijs-Gelling A.J., Gramsbergen J.B. Selective lesions by manganese and extensive damage by iron after injection into rat striatum or hippocampus. J. Neurochem. 62:1994;205-216.
88. Migheli R., Godani C., Sciola L., Delogu M.R., Serra P.A., Zangani D., De Natale G., Miele E., Desole M.S. Enhancing effect of manganese on L-DOPA-induced apoptosis in PC12 cells: role of oxidative stress. J. Neurochem. 73:1999;1155-1163.
89. Luo Y., Bond J.D., Ingram V.M. Compromised mitochondrial function leads to increased cytosolic calcium and to activation of MAP kinases. Proc. Natl. Acad. Sci. U.S.A. 94:1997;9705-9710.
90. ATP channel openers activate the ERK kinase by an oxidant-dependent mechanism. Am. J. Physiol. Cell Physiol. 283:2002;C273-C281.
91. Kitazawa M., Wagner J.R., Kirby M.L., Anantharam V., Kanthasamy A.G. Oxidative stress and mitochondrial-mediated apoptosis in dopaminergic cells exposed to methylcyclopentadienyl manganese tricarbonyl. J. Pharmacol. Exp. Ther. 302:2002;26-35.
92. Desole M.S., Sciola L., Delogu M.R., Migheli R., Sircana S., Migheli R. Manganese and 1-methyl-4-(2′-ethylphenyl)-1,2,3,6-tetrahydropyridine induce apoptosis in PC12 cells. Neurosci. Lett. 209:1996;193-196.
93. Desole M.S., Sciola L., Delogu M.R., Sircana S., Migheli R., Miele E. Role of oxidative stress in the manganese and 1-methyl-4-(2′-ethylphenyl)-1,2,3,6-tetrahydropyridine-induced apoptosis in PC12 cells. Neurochem. Int. 31:1997;169-176.
94. Schrantz N., Blanchard D.A., Mitenne F., Auffredou M.T., Vazquez A., Leca G. Manganese induces apoptosis of human B cells: caspase-dependent cell death blocked by Bcl-2. Cell Death Differ. 6:1999;445-453.
95. Hirata Y. Manganese-induced apoptosis in PC12 cells. Neurotoxicol. Teratol. 24:2002;639-653.
96. 2+ sequestration by mitochondria and inhibition of oxidative phosphorylation. Toxicol. Appl. Pharmacol. 115:1992;1-5.
97. Gavin C.E., Gunter K.K., Gunter T.E. Manganese and calcium transport in mitochondria: implications for manganese toxicity. Neurotoxicology. 20:1999;445-454.
98. Galvani P., Fumagalli P., Santagostino A. Vulnerability of mitochondrial complex I in PC12 cells exposed to manganese. Eur. J. Pharmacol. 293:1995;377-383.
99. Chen C.J., Liao S.L. Oxidative stress involves in astrocytic alterations induced by manganese. Exp. Neurol. 175:2002;216-225.
100. Baader E.W. Manganese poisoning in dry cell battery factories. Arch. Gewerbepathol Gewerbehyg. 4:1932;101-116.
101. Lloyde Davies T.A., Harding H.E. Manganese pneumonitis. Further clinical and experimental evidence. Br. J. Ind. Med. 6:1949;82-90.
102. Rodier J. Manganese poisoning in Moroccan mines. Br. J. Ind. Med. 12:1955;21-35.
103. Bencko V., Cikrt M. Manganese: a review of occupational and environmental toxicology. J. Hyg. Epidemiol. Microbiol. Immunol. 28:1984;139-148.
104. Roels H., Lauwerys R., Buchet J.P., Genet P., Sarhan M.J., Hanotiau I., de Fays M., Bernard A., Stanescu D. Epidemiological survey among workers exposed to manganese: effects on lung, central nervous system, and some biological indices. Am. J. Ind. Med. 11:1987;307-327.
105. Saric M. Occupational and environmental exposures and nonspecific lung disease: a review of selected studies. Isr. J. Med. Sci. 28:1992;509-512.
106. Saric M., Piasek M. Environmental exposure to manganese and combined exposure to gaseous upper respiratory irritants: mechanism of action and adverse health effects. Rev. Environ. Health. 15:2000;413-419.
107. Davis D.W., Hsiao K., Ingels R., Shikiya J. Origins of manganese in air particulates in California. JAPCA. 38:1988;1152-1157.
108. Ressler T., Wong J., Roos J. Manganese speciation in exhaust particles of automobiles using MMT-containing gasoline. J. Synchrotron Rad. 6:1999;656-658.
109. Vitarella D., Wong B.A., Moss O.R., Dorman D.C. Pharmacokinetics of inhaled manganese phosphate in male Sprague-Dawley rats following subacute (14-day) exposure. Toxicol. Appl. Pharmacol. 163:2000;79-85.
110. Crouch E., Wright J.R. Surfactant proteins A and D and pulmonary host defense. Annu. Rev. Physiol. 63:2001;521-554.
111. Mason R.J., Voelker D.R. Regulatory mechanisms of surfactant secretion. Biochim. Biophys. Acta. 1408:1998;226-240.
112. Rice T.M., Clarke R.W., Godleski J.J., Al-Mutairi E., Jiang N.F., Hauser R., Paulauskis J.D. Differential ability of transition metals to induce pulmonary inflammation. Toxicol. Appl. Pharmacol. 177:2001;46-53.
113. Malecki E.A., Devenyi A.G., Beard J.L., Connor J.R. Existing and emerging mechanisms for transport of iron and manganese to the brain. J. Neurosci. Res. 56:1999;113-122.
114. Roth J.A., Feng L., Dolan K.G., Lis A., Garrick M.D. Effect of the iron chelator desferrioxamine on manganese-induced toxicity of rat pheochromocytoma (PC12) cells. J. Neurosci. Res. 68:2002;76-83.
115. Gunshin H., Mackenzie B., Berger U.V., Gunshin Y., Romero M.F., Boron W.F., Nussberger S., Gollan J.L., Hediger M.A. Cloning and characterization of a mammalian proton-coupled metal-ion transporter. Nature. 388:1997;482-488.
116. Fleming M.D., Trenor C.C., Su M.A., Foernzler D., Beier D.R., Dietrich W.F., Andrews N.C. Microcytic anaemia mice have a mutation in Nramp2, a candidate iron transporter gene. Nat. Genet. 16:1997;383-386.
117. Fleming M.D., Romano M.A., Su M.A., Garrick L.M., Garrick M.D., Andrews N.C. Nramp2 is mutated in the anemic Belgrade (b) rat: evidence of a role for Nramp2 in endosomal iron transport. Proc. Natl. Acad. Sci. U.S.A. 95:1998;1148-1153.
118. Lucaciu C.M., Dragu C., Copaescu L., Morariu V.V. Manganese transport through human erythrocyte membranes. An EPR study. Biochim. Biophys. Acta. 1328:1997;90-98.
119. Kannurpatti S.S., Joshi P.G., Joshi N.B. Calcium sequestering ability of mitochondria modulates influx of calcium through glutamate receptor channel. Neurochem. Res. 25:2000;1527-1536.
120. Garrick M, Dolan M. An expression system for a transporter of iron and other metals. In: Armstrong A, editor. Methods in molecular biology, oxidants and antioxidants: ultrastructure and molecular biology protocols. Totowa, NJ: Humana Press; 2002. p. 147-54.
121. Oates P.S., Thomas C., Freitas E., Callow M.J., Morgan E.H. Gene expression of divalent metal transporter 1 and transferrin receptor in duodenum of Belgrade rats. Am. J. Physiol. 278:2000;G930-G936.
122. 2-microglobulin knockout mice. Am. J. Physiol. 283:2002;G687-G694.
123. Mena I., Horiuchi K., Burke K., Cotzias G.C. Chronic manganese poisoning, individual susceptibility and absorption of iron. Neurology. 19:1969;1000-1006.
124. Erikson K.M., Shihabi Z.K., Aschner J.L., Aschner M. Manganese accumulates in iron-deficient rat brain regions in a heterogeneous fashion and is associated with neurochemical alterations. Biol. Trace Elem. Res. 87:2002;143-156.
125. Hubert N., Hentze M.W. Previously uncharacterized isoforms of divalent metal transporter (DMT)-1: implications for regulation and cellular function. Proc. Natl. Acad. Sci. U.S.A. 99:2002;12345-12350.
126. Gruenheid S., Cellier M., Vidal S., Gros P. Identification and characterization of a second mouse Nramp gene. Genomics. 25:1995;514-525.
127. Lee P.L., Gelbart T., West C., Halloran C., Beutler E. The human Nramp2 gene: characterization of the gene structure, alternative splicing, promoter region and polymorphisms. Blood Cells Mol. Dis. 24:1998;199-215.
128. Su M.A., Trenor C.C. III, Fleming J.C., Fleming M.D., Andrews N.C. The G185R mutation disrupts function of the iron transporter Nramp2. Blood. 92:1998;2157-2163.
129. Tchernitchko D., Bourgeois M., Martin M.E., Beaumont C. Expression of the two mRNA isoforms of the iron transporter Nrmap2/DMTI in mice and function of the iron responsive element. Biochem. J. 363:2002;449-455.
130. Haile D.J. Regulation of genes of iron metabolism by the iron-response proteins. Am. J. Med. Sci. 318:1999;230-240.
131. Schümann K., Moret R., Künzle H., Kühn L.C. Iron regulatory protein as an endogenous sensor of iron in rat intestinal mucosa: possible implications for the regulation of iron absorption. Eur. J. Biochem. 260:1999;362-372.
132. Gunshin H., Allerson C.R., Polycarpou-Schwarz M., Rofts A., Rogers J.T., Kishi F., Hentze M.W., Rouault T.A., Andrews N.C., Hediger M.A. Iron-dependent regulation of the divalent metal ion transporter. FEBS Lett. 509:2001;309-316.
133. Wardrop S.L., Wells C., Ravasi T., Hume D.A., Richardson D.R. Induction of Nramp2 in activated mouse macrophages is dissociated from regulation of the Nramp1, classical inflammatory genes, and genes involved in iron metabolism. J. Leukoc. Biol. 71:2002;99-106.
134. LaVaute T., Smith S., Cooperman S., Iwai K., Land W., Meyron-Holtz E., Drake S.K., Miller G., Abu-Asab M., Tsokos M., Switzer R., Grinberg A., Love P., Tresser N., Rouault T.A. Targeted deletion of the gene encoding iron regulatory protein-2 causes misregulation of iron metabolism and neurodegenerative disease in mice. Nat. Genet. 27:2001;209-214.
135. Roth J.A., Horbinski C., Feng L., Dolan K.G., Higgins D., Garrick M.D. Differential localization of divalent metal transporter (DMT1) with and without iron response element (IRE) in rat PC12 and sympathetic neuronal cells. J. Neurosci. 20:2000;7595-7601.
136. Wang X., Ghio A.J., Yang F., Dolan K.G., Garrick M.D., Piantadosi C.A. Iron uptake and Nramp2/DMT1/DCT1 in human bronchial epithelial cells. Am. J. Physiol. Lung Cell Mol. Physiol. 282:2002;L987-L995.
137. Garrick M., Scott D., Walpole S., Finkelstein E., Whitbred J., Chopra S., Trivikram L., Mayes D., Rhodes D., Cabbagestalk K., Oklu R., Sadiq A., Mascia B., Hoke J., Garrick L. Iron supplementation moderates but does not cure the Belgrade anemia. Biometals. 10:1997;65-76.
138. Farcich E.A., Morgan E.H. Diminished iron acquisition by cells and tissues of Belgrade laboratory rats. Am. J. Physiol. 262:1992;R220-R224.
139. Burdo J.R., Martin J., Menzies S.L., Dolan K.G., Romano M.A., Fletcher R.J., Garrick M.D., Garrick L.M., Connor J.R. Cellular distribution of iron in the brain of the Belgrade rat. Neuroscience. 93:1999;1189-1196.
140. * mapping of reduced brain iron in the Belgrade rat. Ann. Neurol. 52:2002;102-105.
141. Aschner M., Shanker G., Erikson K., Yang J., Mutkus L.A. The uptake of manganese in brain endothelial cultures. Neurotoxicology. 23:2002;165-168.
142. Jefferies W.A., Brandon M.R., Hunt S.V., Williams A.F., Gatter K.C., Mason D.Y. Transferrin receptor on endothelium of brain capillaries. Nature. 312:1984;162-163.
143. Giometto B., Bozza F., Argentiero V., Gallo P., Pagni S., Piccinno M.G., Tavolato B. Transferrin receptors in rat central nervous system. An immunocytochemical study. J. Neurol. Sci. 98:1990;81-90.
144. Raub T.J., Newton C.R. Recycling kinetics and transcytosis of transferrin in primary cultures of bovine brain microvessel endothelial cells. J. Cell Physiol. 149:1991;141-151.
145. Heltianu C., Serban G., Alexandru V., Gafencu A., Simionescu N., Simionescu M. Expression of transferrin receptors in endothelial cells transfected by electroporation. Eur. J. Cell Biol. 72:1997;79-89.
146. Chua A.C., Morgan E.H. Manganese metabolism is impaired in the Belgrade laboratory rat. J. Comp. Physiol. [B]. 167:1997;361-369.
147. Tjalve H., Henriksson J. Uptake of metals in the brain via olfactory pathways. Neurotoxicology. 20:1999;181-195.
148. 2 ) to the rat brain: toxicokinetic investigations in a unilateral nasal occlusion model Toxicol. Appl. Pharmacol. 169:2000;238-248.
149. Roy C.N., Andrews N.C. Recent advances in disorders of iron metabolism: mutations, mechanisms and modifiers. Hum. Mol. Genet. 10:2001;2181-2186.
150. Burdo J.R., Menzies S.L., Simpson I.A., Garrick L.M., Garrick M.D., Dolan K.G., Haile D.J., Beard J.L., Connor J.R. Distribution of divalent metal transporter 1 and metal transport protein 1 in the normal and Belgrade rat. J. Neurosci. Res. 66:2001;1198-1207.
151. Le N.T., Richardson D.R. Ferroportin1: a new iron export molecule? Int. J. Biochem. Cell Biol. 34:2002;103-108.
152. Shoham S., Youdim M.B.H. Iron involvement in neural damage and microgliosis in models of neurodegenerative diseases. Cell. Mol. Biol. 46:2000;743-760.
153. Halliwell B. Role of free radicals in the neurodegenerative diseases: therapeutic implications for antioxidant treatment. Drugs Aging. 18:2001;685-716.
154. Thompson K.J., Shoham S., Connor J.R. Iron and neurodegenerative disorders. Brain Res. Bull. 55:2001;155-164.
155. Aisen P., Enns C., Wessling-Resnick M. Chemistry and biology of eukaryotic iron metabolism. Int. J. Biochem. Cell Biol. 33:2001;940-959.
156. Berg D., Gerlach M., Youdim M.B., Double K.L., Zecca L., Riederer P., Becker G. Brain iron pathways and their relevance to Parkinson's disease. J. Neurochem. 79:2001;225-236.
157. Conrad M.E., Umbreit J.N. Iron absorption and transport - an update. Am. J. Hematol. 64:2000;287-298.
158. Umbreit J.N., Conrad M.E., Hainsworth L.N., Simovich M. The ferrireductase paraferritin contains divalent metal transporter as well as mobilferrin. Am. J. Physiol. Gastrointest. Liver Physiol. 282:2002;G534-G539.
159. Malecki E.A., Devenyi A.G., Barron T.F., Mosher T.J., Eslinger P., Flaherty-Craig C.V., Rossaro L. Iron and manganese homeostasis in chronic liver disease: relationship to pallidal T1-weighted magnetic resonance signal hyperintensity. Neurotoxicology. 20:1999;647-652.