The aryl hydrocarbon receptor nuclear translocator (ARNT) modulates the antioxidant response in AML cells.
We observed AML cell lines vary in their sensitivity to induction of apoptosis by troglitazone (TG), which induces apoptosis through the generation of intracellular reactive oxygen species (ROS). TG-resistant cell lines had increased abundance of ARNT transcripts and protein. Expression of ARNT in TG-sensitive cells made these cells resistant to both TG and daunorubicin. ARNT-expressing cells had increased expression of SOD2 and Nrf2 transcripts and elevated intracellular GSH concentration. Our results indicate that ARNT expression in AML cells augments antioxidant response and confers resistance to ROS inducers. This suggests ARNT may modulate ROS signaling and drug response in AML.
The J. Douglas Crashley MDS Research Laboratory, Sunnybrook Research Institute, 2075 Bayview Avenue, Toronto, ON M4N 3M5, Canada.
Chunhong
C
Gu
Joelle
J
Gonzalez
Tong
T
Zhang
Suzanne
S
Kamel-Reid
Richard A
RA
Wells
D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator / Q000502:physiology*; D002478:Cells, Cultured; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D020869:Gene Expression Profiling; D015973:Gene Expression Regulation, Leukemic; D018922:HL-60 Cells; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D046228:Microarray Analysis; D041681:NIH 3T3 Cells; D018384:Oxidative Stress / Q000235:genetics*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013312:Stress, Physiological / Q000235:genetics; D020298:U937 Cells
C497396:ARNT protein, human; D000975:Antioxidants; D017382:Reactive Oxygen Species; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator
ARNT; Chemoresistance; Hypoxia-inducible factor; Oxidative stress; Reactive oxygen species