S-Adenosylmethionine decarboxylase partially regulates cell growth of HL-60 cells by controlling the intracellular ROS level: Early senescence and sensitization to γ-radiation

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Title
S-Adenosylmethionine decarboxylase partially regulates cell growth of HL-60 cells by controlling the intracellular ROS level: Early senescence and sensitization to γ-radiation
Author(s)
J S Kim; T L Kim; K C Kim; C Choe; H W Chung; Eun Wie Cho; I G Kim
Bibliographic Citation
Archives of Biochemistry and Biophysics, vol. 456, no. 1, pp. 58-70
Publication Year
2006
Abstract
S-Adenosylmethionine decarboxylase (SAMDC) is a key enzyme for the biosynthesis of spermidine. SAMDC-suppressed HL-60 cells overproduced intracellular reactive oxygen species (ROS), which led to cell growth defect and partial cell death. ROS overproduction was caused by a decrease of the total glutathione (GSH) and the ratio of reduced to oxidized GSH, and by an increase of the intracellular iron uptake. When analyzed by real-time polymerase chain reaction, the transcripts of the genes involved in the GSH synthesis (γ-glutamyl cysteine synthetase, GSH synthetase), as well as the gene of the GSH-reducing enzyme (NADP+-dependent isocitrate dehydrogenase), were decreased dramatically in these cells. DNA-repairing genes (ATM, PARP, RAD51 and MSH2) also were not activated transcriptionally. In these situations, excessive ROS induced severe DNA damage, which could not be repaired, and ultimately led the cells to a spontaneous cell death or an early senescence state. For such cells, γ-radiation and cisplatin, which are direct DNA-damaging agents, were very effective for promoting cell death.
Keyword
cell deathDNA damageDNA repairingglutathione synthesisiron uptakeSAMDCsenescencespermidineROS
ISSN
0096-9621
Publisher
Elsevier
DOI
http://dx.doi.org/10.1016/j.abb.2006.09.020
Type
Article
Appears in Collections:
Division of Biomedical Research > Rare Disease Research Center > 1. Journal Articles
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