hMTH1 depletion promotes oxidative-stress-induced apoptosis through a Noxa- and caspase-3/7-mediated signaling pathway

DNA Repair
Cha-Kyung YounHo Jin You

Abstract

Although the accumulation of 8-oxo-dGTP in DNA is associated with apoptotic cell death and mutagenesis, little is known about the exact mechanism of hMTH1-mediated suppression of oxidative-stress-induced cell death. Therefore, we investigated the regulation of DNA-damage-related apoptosis induced by oxidative stress using control and hMTH1 knockdown cells. Small interfering RNA (siRNA) was used to suppress hMTH1 expression in p53-proficient GM00637 and H460 cells, resulting in a significant increase in apoptotic cell death after H(2)O(2) exposure; however, p53-null, hMTH1-deficient H1299 cells did not exhibit H(2)O(2)-induced apoptosis. In addition, hMTH1-deficient GM00637 and H460 cells showed increased caspase-3/7 activity, cleaved caspase-8, and Noxa expression, and gamma-H2AX formation in response to H(2)O(2). In contrast, the caspase inhibitors, p53-siRNA, and Noxa-siRNA suppressed H(2)O(2)-induced cell death. Moreover, in 8-week (long-term) cultured H460 and H1299 cells, hMTH1 suppression increased cell death, Noxa expression, and gamma-H2AX after H(2)O(2) exposure, compared to 3-week (short-term) cultured cells. These data indicate that hMTH1 plays an important role in protecting cells against H(2)O(2)-induced apoptosis ...Continue Reading

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Citations

May 8, 2014·DNA Repair·Fabian Sanchis-GomarAlejandro Lucía
Nov 30, 2010·DNA Repair·Katarzyna D ArczewskaHilde Nilsen
Sep 25, 2019·Cancers·Marcella CamiciMaria Grazia Tozzi
Jan 12, 2020·Biochimica Et Biophysica Acta. Molecular Cell Research·John HuangJun Ling

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