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p38 mitogen-activated protein kinase is a key regulator of 5-phenylselenyl- and 5-methylselenyl-methyl-2'-deoxyuridine-induced apoptosis in human HL-60 cells

Authors
 Byeong Mo Kim  ;  Kee-Ho Lee  ;  In Seok Hong  ;  Sung Hee Hong 
Citation
 BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, Vol.417(1) : 237-244, 2012 
Journal Title
 BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 
ISSN
 0006-291X 
Issue Date
2012
MeSH
Apoptosis/drug effects* ; Caspase 2/biosynthesis ; Caspase 3/biosynthesis ; Caspase 8/biosynthesis ; DNA Damage ; Deoxyuridine/analogs & derivatives* ; Deoxyuridine/pharmacology ; Enzyme Activation ; Enzyme Inhibitors/pharmacology ; Flavonoids/pharmacology ; HL-60 Cells ; Humans ; Imidazoles/pharmacology ; Organoselenium Compounds/pharmacology* ; Poly(ADP-ribose) Polymerases/metabolism ; Pyridines/pharmacology ; Reactive Oxygen Species/metabolism ; p38 Mitogen-Activated Protein Kinases/antagonists & inhibitors ; p38 Mitogen-Activated Protein Kinases/metabolism*
Abstract
Two novel, modified thymidine nucleosides, 5-phenylselenyl-methyl-2'-deoxyuridine (PhSe-T) and 5-methylselenyl-methyl-2'-deoxyuridine (MeSe-T), trigger reactive oxygen species (ROS) generation and DNA damage and thereby induce caspase-mediated apoptosis in human HL-60 cells; however, the mechanism leading to caspase activation and apoptotic cell death remains unclear. Therefore, we investigated the signaling molecules involved in nucleoside derivative-induced caspase activation and apoptosis in HL-60 cells. PhSe-T/MeSe-T treatment activated two mitogen-activated protein kinases (MAPKs), extracellular-receptor kinase (ERK) and p38, and induced the phosphorylation of two downstream targets of p38, ATF-2 and MAPKAPK2. In addition, the selective p38 inhibitor SB203580 suppressed PhSe-T/MeSe-T-induced apoptosis and activation of caspase-3, -9, -8, and -2, whereas the jun amino-terminal kinase (JNK) inhibitor SP600125 and the ERK inhibitor PD98059 had no effect. SB203580 and an ROS scavenger, tiron, inhibited PhSe-T/MeSe-T-induced histone H2AX phosphorylation, which is a DNA damage marker. Moreover, tiron inhibited PhSe-T/MeSe-T-induced phosphorylation of p38 and enhanced p38 MAP kinase activity, indicating a role for ROS in PhSe-T/MeSe-T-induced p38 activation. Taken together, our results suggest that PhSe-T/MeSe-T-induced apoptosis is mediated by the p38 pathway and that p38 serves as a link between ROS generation and DNA damage/caspase activation in HL-60 cells.
Full Text
https://www.sciencedirect.com/science/article/pii/S0006291X11021139
DOI
10.1016/j.bbrc.2011.11.092
Appears in Collections:
5. Research Institutes (연구소) > Yonsei Integrative Research Institute for Cerebral & Cardiovascular Disease (뇌심혈관질환융합연구사업단) > 1. Journal Papers
Yonsei Authors
Kim, Byeong Mo(김병모) ORCID logo https://orcid.org/0000-0002-0582-3132
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/158296
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