Gene expression in enhanced apoptosis of human lymphoma U937 cells treated with the combination of different free radical generators and hyperthermia.
The effects of various free radicals derived from 6-formylpterin (6-FP), alpha-phenyl-tert-butyl nitrone (PBN) and 2,2'-azobis (2-amidinopropane) dihydrochloride (AAPH) combined with hyperthermia, on gene expression in similarly enhanced apoptosis of human lymphoma U937 cells were investigated using cDNA microarrays containing approximately 16,600 genes and computational gene expression analysis tools. When the cells were treated for 10 min at 44 degrees C (15% apoptosis level), 39 up-regulated and 3 down-regulated genes were identified. In the up-regulated genes, apoptosis- and unfolded protein response-associated genes were contained. The combined treatment with heat and either chemical enhanced apoptosis level (approximately 30%) and showed a chemical-specific gene expression pattern. Furthermore, the expression levels of selected genes were confirmed by a real-time quantitative PCR. The present results will provide a basis for further understanding the molecular mechanisms in enhancement of heat-induced apoptosis by different intracellular oxidative stress.
Wada
Shigehito
S
Department of Oral and Maxillofacial Surgery, Faculty of Medicine, University of Toyama, Toyama, 930-0194, Japan.
Tabuchi
Yoshiaki
Y
Kondo
Takashi
T
Cui
Zheng-Guo
ZG
Zhao
Qing-Li
QL
Takasaki
Ichiro
I
Salunga
Thucydides L
TL
Ogawa
Ryohei
R
Arai
Toshiyuki
T
Makino
Keisuke
K
Furuta
Isao
I
D000578:Amidines / Q000494:pharmacology; D017209:Apoptosis / Q000502:physiology*; D045744:Cell Line, Tumor; D003497:Cyclic N-Oxides / Q000494:pharmacology; D005334:Fever / Q000378:metabolism / Q000503:physiopathology*; D005609:Free Radicals / Q000378:metabolism*; D015870:Gene Expression / Q000502:physiology*; D020869:Gene Expression Profiling; D006801:Humans; D008223:Lymphoma / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D016877:Oxidants / Q000494:pharmacology; D018384:Oxidative Stress / Q000502:physiology*; D011622:Pterins / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000578:Amidines; D003497:Cyclic N-Oxides; D005609:Free Radicals; D016877:Oxidants; D011622:Pterins; C029217:phenyl-N-tert-butylnitrone; C005926:2-amino-4-hydroxy-6-formylpteridine; C046728:2,2'-azobis(2-amidinopropane)