Summary
In neurodegenerative diseases, including Parkinson’s and Alzheimer’s diseases, apoptosis is a common type of cell death, and mitochondria emerge as the major organelle to initiate death cascade. Monoamine oxidase (MAO) in the mitochondrial outer membrane produces hydrogen peroxide by oxidation of monoamine substrates, and induces oxidative stress resulting in neuronal degeneration. On the other hand, a series of inhibitors of type B MAO (MAO-B) protect neurons from cell death. These results suggest that MAO may be involved in the cell death process initiated in mitochondria. However, the direct involvement of MAO in the apoptotic signaling has been scarcely reported. In this paper, we present our recent results on the role of MAO in activating and regulating cell death processing in mitochondria. Type A MAO (MAO-A) was found to bind an endogenous dopaminergic neurotoxin, N-methyl(R)salsolinol, and induce apoptosis in dopaminergic SH-SY5Y cells containing only MAO-A. To examine the intervention of MAO-B in apoptotic process, human MAO-B cDNA was transfected to SH-SY5Y cells, but the sensitivity to N-methyl(R)salsolinol was not affected, even though the activity and protein of MAO-B were expressed markedly. MAO-B oxidized dopamine with production of hydrogen peroxide, whereas in control cells expressing only MAO-A, dopamine autoxidation produced superoxide and dopamine-quinone, and induced mitochondrial permeability transition and apoptosis. Rasagiline and other MAO-B inhibitors prevent the activation of apoptotic cascade and induce prosurvival genes, such as bcl-2 and glial cell line-derived neurotrophic factor, in MAO-A-containing cells. These results demonstrate a novel function of MAO-A in the induction and regulation of apoptosis. Future studies will clarify more detailed mechanism behind regulation of mitochondrial death signaling by MAO-A, and bring out new strategies to cure or ameliorate the decline of neurons in neurodegenerative disorders.
Access provided by Autonomous University of Puebla. Download to read the full chapter text
Chapter PDF
Similar content being viewed by others
Keywords
- Monoamine Oxidase
- Dopamine Oxidation
- Endogenous Neurotoxin
- Regulate Cell Death Processing
- Mitochondrial Death Signaling
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
References
Akao Y, Maruyama W, Shimizu S, Yi H, Nakagawa Y, Shamoto-Nagai M, Youdim MBH, Tsujimoto Y, Naoi M (2002a) Mitochondrial permeability transition mediates apoptosis induced by N-methyl(R)salsolinol, an endogenous neurotoxin, and is inhibited by Bcl-2 and rasagiline, N-propargyl-1(R)-aminoindan. J Neurochem 82: 913–923
Akao Y, Maruyama W, Yi H, Shamoto-Nagai M, Youdim MBH, Naoi M (2002b) An anti-Parkinson’s disease drug, N-propargyl-1(R)-aminoindan (rasagiline), enhances expression of anti-apoptotic bcl-2 in human dopaminergic SH-SY5Y cells. Neurosci Lett 326: 10510–10518
Andersen JK (2004) Oxidative stress in neurodegeneration: cause or consequence? Nature Med 10: S18–S25
Bach AWJ, Lan NC, Johnson DL, Abell CW, Bembenek ME, Kwan S-W, Seeburg PH, Shih JC (1988) cDNA cloning of human monoamine oxidase A and B: Molecular basis of differences in enzymatic properties. Proc Natl Acad Sci USA 85: 4934–4938
Bindokas VP, Jordan J, Lee CC, Miller RJ (1996) Superoxide production in rat hippocampal neurons: Selective imaging with hydroethidine. J Neurosci 16: 1324–1336
Bossy-Wetzel E, Schwarzenbacher R, Lipton S (2004) Molecular pathways to neurodegeneration. Nature Med 10: S2–S9
Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein using the principle of protein dye binding. Anal Biochem 72: 248–254
Carrillo MC, Minami C, Kitani K, Maruyama W, Ohashi K, Yamamoto T, Naoi M, Kanai S, Youdim MBH (2000) Enhancing effect of rasagiline on superoxide dismutase and catalase activities in the dopaminergic system in the rat. Life Sci 67: 577–585
Cases O, Seif I, Grimsby J, Gaspa P, Chen K, Pounin S, Müller U, Aguet M, Babinet C, Shih JC, De Maeyer E (1995) Aggressive behavior and altered amounts of brain serotonin and norepinephrine in mice lacking MAOA. Science 268: 1763–1766
Cohen G, Farooqui R, Kesler N (1997) Parkinson disease: a new link between monoamine oxidase and mitochondrial electron flow. Proc Natl Acad Sci USA 94: 4890–4897
Crompton M (1999) The mitochondrial permeability transition pore and its role in the cell death. Biochem J 341: 233–249
Crow JP (1997) Dichlorodihydrofluorescein and dihydrorhodamine 123 are selective indicators of peroxynitrite in vitro: Implications for intracellular measurement of reactive nitrogen and oxygen species. Nitric Oxide 1: 145–157
Damier P, Kastner A, Agid Y, Hirsch EC (1996) Does monoamine oxidase type B play a role in dopaminergic nerve cell death in Parkinson’s disease? Neurology 46: 1262–1269
Desagher S, Osen-Sand A, Nichols A, Eskes R, Montessuit S, Lauper S, Maundrell K, Amtonsson B, Martinou J-C (1999) Bid-induced conformational change of Bax is responsible for mitochondrial cytochrome c release during apoptosis. J Cell Biol 144: 891–901
DeZutter GS, Davis RJ (2001) Pro-apoptotic gene expression mediated by the p38 mitogen-activated protein kinase signal transduction pathway. Proc Natl Acad Sci USA 98: 6168–6173
Eckert A, Steiner B, Marques C, Leutz S, Roming H, Haass C, Muller WE (2001) Elevated vulnerability to oxidative tress-induced cell death and activation of caspase-3 by the Swedish amyloid precursor protein mutation. J Neurosci Res 64: 183–192
Gargalidis-Moudanos C, Femaury A, Parini A (1997) Predominant expression of monoamine oxidase B isoform in rabbit renal proximal tubule: Regulation by I2 imidazoline ligands in intact cells. Mol Pharmacol 51: 637–643
Götz MF, Freyberger A, Riederer P (1990) Oxidative stress: a role in the pathogenesis of Parkinson’s disease. J Neural Transm [Suppl 29]: 241–249
Green DR, Kroemer G (2004) The pathophysiology of mitochondrial cell death. Science 305: 626–269
Heikkila RE, Manzimo L, Cabbat FS, Duvoisin RC (1985) Studies on the oxidation of the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,5-tetrahydropyridine by monoamine oxidase B. J Neurochem 45: 1049–1054
Kraml M (1965) A rapid microfluorometric determination of monoamine oxidase. Biochem Pharmacol 14: 1684–1686
Lan NC, Chen C, Shih JC (1989) Expression of functional human monoamine oxidase A and B cDNAs in mammalian cells. J Neurochem 52: 1625–1634
Lim LCC, Powell JF, Murray R, Gill M (1994) Monoamine oxidase A gene and bipolar affective disorder. Am J Hum Genet 54: 1122–1124
Malorni W, Giammarioli AM, Matarrese P, Piertrangeli P, Agostinelli E, Ciaccio A, Grassilli E, Mondovi N (1998) Protection against apoptosis by monoamine oxidase A inhibitors. FEBS Lett 426: 155–159
Marcocci L, De Marchi U, Salvi M, Milella ZG, Nocera S, Agostinelli E, Mondovi B, Toninello A (2002) Tyramine and monoamine oxidase inhibitors as modulators of the mitochondrial membrane permeability transition. J Membrane Biol 188: 23–31
Maruyama W, Abe T, Tohgi H, Dostert P, Naoi M (1996) A dopaminergic neurotoxin, (R)-N-methylsalsolinol, increases in Parkinsonian cerebrospinal fluid. An Neurol 40: 119–122
Maruyama W, Naoi M, Kasamatsu T, Hashizume Y, Takahashi T, Kohda K, Dostert P (1997) An endogenous dopaminergic neurotoxin, N-methyl-(R)-salsolinol, induces DNA damage in human dopaminergic neuroblastoma SH-SY5Y cells. J Neurochem 69: 322–329
Maruyama W, Akao Y, Youdim MBH, Davis BA, Naoi M (2001a) Transfection-forced Bcl-2 overexpression and anti-Parkinson drug, rasagiline, prevent nuclear translocation of glyceraldehydes-3-phosphate dehydrogenase induced by an endogenous dopaminergic neurotoxin, N-methyl(R)salsolinol. J Neurochem 78: 727–735
Maruyama W, Boulton AA, Davis BA, Dostert P, Naoi M (2001b) Enantiospecific induction of apoptosis by an endogenous neurotoxin Nmethyl(R)salsolinol, in dopaminergic SH-SY5Y cells: suppression of apoptosis by N-(2-heptyl)-N-methylpropargylamine. J Neural Transm 108: 11–24
Maruyama W, Youdim MBH, Naoi M (2001c) Antiapoptotic properties of rasagiline, N-propargylamine-1(R)-aminoindan, and its optical (S)-isomer, TV1022. Ann NY Acad Sci 939: 320–329
Maruyama W, Nitta A, Shamoto-Nagai M, Hirata Y, Akao Y, Youdim M, Furukawa S, Nabeshima T, Naoi M (2004) N-Propargyl-1(R)-aminoindan, rasagiline, increases glial cell line-derived neurotrophic factor (GDNF) in neuroblastoma SH-SY5Y cells through activation of NF-κB transcription factor. Neurochem Int 44: 393–400
Naoi M, Maruyama W, Dostert P, Hashizume Y, Nakahara D, Takahashi T, Ota M (1996) Dopamine-derived endogenous 1(R),2(N)-dimethyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline, N-methyl-(R)-salsolinol, induced parkinsonism in rat: Biochemical, pathological and behavioral studies. Brain Res 709: 285–295
Naoi M, Maruyama W, Nakao N, Ibi T, Sahashi K, Strolin Benedetti M (1998) (R)Salsolinol N-methyltransferase activity increases in parkinsonian lymphocytes. Ann Neurol 43: 212–216
Naoi M, Maruyama W, Akao Y, Yi H (2002a) Mitochondria determine the survival and death in apoptosis induced by an endogenous neurotoxin, N-methyl(R)salsolinol, and neuroprotection by propargylamines. J Neural Transm [Suppl 109]: 607–621
Naoi M, Maruyama W, Akao Y, Yi H (2002b) Dopamine-derived endogenous N-methyl-(R)-salsolinol. Its role in Parkinson’s disease. Neurotoxicol Tera 24: 579–591
Naoi M, Maruyama W, Nagy GM (2004) Dopamine-derived salsolinol derivatives as endogenous monoamine oxidase inhibitors: Occurrence. Metabolism and function in human brains. NeuroToxicol 25: 193–204
Naoi M, Maruyama W, Shamoto-Nagai M, Yi H, Akao Y, Tanaka M (2005) Oxidative stress in mitochondria; decision to survival and death of neurons in neurodegenertaion. Mol Neurobiol 31: 81–93
O’Caroll AM, Fowler CJ, Phillips JP, Tobia I, Tipton KF (1988) The deamination of dopamine by human brain monoamine oxidase. Arch Pharmacol 322: 198–223
Parkinson Study Group (2004) A controlled, randomized, delayed-start study of rasagiline in early Parkinson disease. Arch Neurol 61: 561–566
Shih JC, Chen K, Ridd MJ (1999) Monoamine oxidase: from genes to behavior. Annu Rev Neurosci 22: 197–217
Teitel S, O’Brien J, Brossi A (1972) Alkaloids in mammalian tissue II. Synthesis of (+) and (−)substituted 6,7-dihydroxy-1,2,3,4-tetrahydroisoquinolines. J Med Chem 15: 845–846
Tipton KF, Boyce S, O’Sullivan J, Davey GP, Healy J (2004) Monoamine oxidases: Certainties and uncertainties. Curr Med Chem 11: 1965–1982
Westlund KN, Denney RM, Rose RM, Abell CW (1988) Localization of distinct monoamine oxidase A and monoamine oxidase B cell populations in human brainstem. Neuroscience 25: 439–456
Wong WK, Chen K, Shih JC (2003) Decreased methylation and transcription repressor Sp3 up-regulated human monoamine oxidase (MAO) B expression during Caco-2 differentiation. J Biol Chem 278: 36227–36235
Yi H, Maruyama W, Akao Y, Takahashi T, Iwasa K, Youdim MBH, Naoi M (2006) N-Propargylamine protects SH-SY5Y cells from apoptosis induced by an endogenous neurotoxin, N-methyl(R)salsolinol, through stabilization of mitochondrial membrane and induction of anti-apoptotic Bcl-2. J Neural Transm 113: 21–32
Yi H, Akao Y, Maruyama W, Chen K, Shih J, Naoi M (2006) Type A monoamine oxidase is the target of an endogenous dopaminergic neurotoxin, N-Methyl(R)salsolinol, leading to apoptosis in SH-SY5Y cells. J Neurochem 96: 541–549
Youdim MBH, Gross A, Finberg JPM (2001) Rasagiline [N-propargyl-1R(+)-aminoindan], a selective and potent inhibitor of mitochondrial monoamine oxidase B. Br J Pharmacol 132: 500–506
Youdim MBH, Maruyama W, Naoi M (2005) Neuropharmacological, neuroprotective and amyloid precursor processing properties of selective MAO-B inhibitor antiparkinsonian drug, rasagiline. Drug Today 41: 369–391
Youdim MBH, Bar Am O, Yogev-Falach M, Weinreb O, Maruyama W, Naoi M, Amit T (2005b) Rasagiline: neurodegeneration, neuroprotection, and mitochondrial permeability transition. J Neurochem Res 79: 172–179
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2006 Springer-Verlag
About this chapter
Cite this chapter
Naoi, M., Maruyama, W., Akao, Y., Yi, H., Yamaoka, Y. (2006). Involvement of type A monoamine oxidase in neurodegeneration: regulation of mitochondrial signaling leading to cell death or neuroprotection. In: Parvez, H., Riederer, P. (eds) Oxidative Stress and Neuroprotection. Journal of Neural Transmission. Supplementa, vol 71. Springer, Vienna. https://doi.org/10.1007/978-3-211-33328-0_8
Download citation
DOI: https://doi.org/10.1007/978-3-211-33328-0_8
Publisher Name: Springer, Vienna
Print ISBN: 978-3-211-33327-3
Online ISBN: 978-3-211-33328-0
eBook Packages: MedicineMedicine (R0)