S-Adenosylmethionine decarboxylase partially regulates cell growth of HL-60 cells by controlling the intracellular ROS level: Early senescence and sensitization to gamma-radiation.
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 (gamma-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, gamma-radiation and cisplatin, which are direct DNA-damaging agents, were very effective for promoting cell death.
Kim
Jin Sik
JS
Department of Radiation Biology, Environment Radiation Research Group, Korea Atomic Energy Research Institute, Yuseong, Daejeon 305-600, Republic of Korea.
Kim
Tae Lim
TL
Kim
Kug Chan
KC
Choe
Chungyoul
C
Chung
Hai Won
HW
Cho
Eun Wie
EW
Kim
In Gyu
IG
D012437:Adenosylmethionine Decarboxylase / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D049109:Cell Proliferation / Q000187:drug effects* / Q000528:radiation effects*; D016922:Cellular Senescence / Q000187:drug effects* / Q000528:radiation effects*; D004307:Dose-Response Relationship, Radiation; D005720:Gamma Rays; D018922:HL-60 Cells; D006801:Humans; D011829:Radiation Dosage; D011836:Radiation Tolerance / Q000187:drug effects / Q000528:radiation effects; D017382:Reactive Oxygen Species / Q000378:metabolism*
D000970:Antineoplastic Agents; D017382:Reactive Oxygen Species; D012437:Adenosylmethionine Decarboxylase