An oxidized purine nucleoside triphosphatase, MTH1 suppresses cell death caused by oxidative stress
作者： Daisuke Yoshimura , Kunihiko Sakumi , Mizuki Ohno , Yasunari Sakai , Masato Furuichi
关键词: Caspase 、 Molecular biology 、 Cell 、 Purine 、 Biology 、 Nucleotide 、 Mitochondrion 、 Pyknosis 、 Programmed cell death 、 Nucleoside
摘要: MTH1 hydrolyzes oxidized purine nucleoside triphosphates such as 8-oxo-2′-deoxyguanosine 5′-triphosphate (8-oxo-dGTP) and 2-hydroxy-2′-deoxyadenosine (2-OH-dATP) thus protects cells from damage caused by their misincorporation into DNA. In the present study, we established MTH1-null mouse embryo fibroblasts that were highly susceptible to cell dysfunction death exposure H2O2, with morphological features of pyknosis electron-dense deposits accumulated in mitochondria. The observed was independent both poly(ADP-ribose) polymerase caspases. A high performance liquid chromatography tandem mass spectrometry analysis immunofluorescence microscopy revealed a continuous accumulation 8-oxo-guanine nuclear mitochondrial DNA after H2O2. All H2O2-induced alterations effectively suppressed expression wild type human (hMTH1), whereas they only partially mutant hMTH1 defective either 8-oxo-dGTPase or 2-OH-dATPase activity. Human hydrolyzing nucleotides including 8-oxo-dGTP 2-OH-dATP, these may be partly attributed dysfunction.
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