MTH1, an oxidized purine nucleoside triphosphatase, prevents the cytotoxicity and neurotoxicity of oxidized purine nucleotides.
In human and rodent cells, MTH1, an oxidized purine nucleoside triphosphatase, efficiently hydrolyzes oxidized dGTP, GTP, dATP and ATP such as 2'-deoxy-8-oxoguanosine triphosphate (8-oxo-dGTP) and 2'-deoxy-2-hydroxyadenosine triphosphate (2-OH-dATP) in nucleotide pools, thus avoiding their incorporation into DNA or RNA. MTH1 is expressed in postmitotic neurons as well as in proliferative tissues, and it is localized both in the mitochondria and nucleus, thus suggesting that MTH1 plays an important role in the prevention of the mutagenicity and cytotoxicity of such oxidized purines as 8-oxoG which are known to accumulate in the cellular genome. Our recent studies with MTH1-deficient mice or cells revealed that MTH1 efficiently minimizes accumulation of 8-oxoG in both nuclear and mitochondrial DNA in the mouse brain as well as in cultured cells, thus contributing to the protection of the brain from oxidative stress.
Nakabeppu
Yusaku
Y
Division of Neurofunctional Genomics, Department of Immunobiology and Neuroscience, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Fukuoka 812-8582, Japan. yusaku@bioreg.kyuhsu-u.ac.jp
Kajitani
Kosuke
K
Sakamoto
Katsumi
K
Yamaguchi
Hiroo
H
Tsuchimoto
Daisuke
D
D000544:Alzheimer Disease / Q000378:metabolism; D000690:Amyotrophic Lateral Sclerosis / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism; D003603:Cytotoxins / Q000378:metabolism / Q000633:toxicity; D045647:DNA Glycosylases / Q000378:metabolism; D004260:DNA Repair; D045643:DNA Repair Enzymes / Q000378:metabolism; D006151:Guanosine / Q000031:analogs & derivatives / Q000378:metabolism / Q000633:toxicity; D006801:Humans; D051379:Mice; D009498:Neurotoxins / Q000378:metabolism / Q000633:toxicity; D010084:Oxidation-Reduction; D010300:Parkinson Disease / Q000378:metabolism; D020734:Parkinsonian Disorders / Q000378:metabolism; D010744:Phosphoric Monoester Hydrolases / Q000172:deficiency / Q000378:metabolism*; D011685:Purine Nucleotides / Q000378:metabolism* / Q000633:toxicity*
D003603:Cytotoxins; D009498:Neurotoxins; D011685:Purine Nucleotides; D006151:Guanosine; C046215:8-hydroxyguanosine; D010744:Phosphoric Monoester Hydrolases; D045647:DNA Glycosylases; C479058:oxoguanine glycosylase 1, human; C078207:8-oxodGTPase; C509779:Nudt1 protein, mouse; D045643:DNA Repair Enzymes