Oxidative stress is involved in inhibition of copper on histone acetylation in cells.
Our previous study demonstrates that copper induces histone hypoacetylation by inhibiting histone acetyltransferase (HAT) activity. However, it lacks direct evidences whether copper-inhibited histone acetylation right contributes to the toxicity of copper. Exposure of human leukemia cells (HL-60) to Cu2+ resulted in cell proliferation arrest and a concentration- and time-dependent decrease of histone acetylation. At the same time, Cu2+-induced significant increase of H2O2 and O2.- generation via a concentration- and time-dependent manner too. The histone acetylation was efficiently suppressed by exogenous H2O2, and enhanced by superoxide dismutase (the scavenger of O2.-), catalase (the scavenger of H2O2) or the combination of both, indicating that Cu2+ at least partially inhibited histone acetylation through triggering oxidative stress. Further studies found that sodium butyrate, the inhibitor of histone deacetylase (HDAC), which had no obvious effect on oxidative stress but increased histone acetylation at the concentration of 50 microM, attenuated Cu2+-inhibited cell proliferation, indicating that histone acetylation inhibition is simultaneously involved in the cytotoxicity of Cu2+. Considering the important role of histone acetylation in gene transcription and regulation of cell fate, the present study may open a new door to further understand the mechanism of Cu2+-induced toxicity.
Lin
Changjun
C
School of Life Sciences, Lanzhou University, Tianshui South Road 222, Lanzhou 730000, China.
Kang
Jiuhong
J
Zheng
Rongliang
R
D000107:Acetylation; D002374:Catalase / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D003300:Copper / Q000494:pharmacology*; D004249:DNA Damage; D018922:HL-60 Cells; D006657:Histones / Q000378:metabolism*; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D007700:Kinetics; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism
D006657:Histones; D017382:Reactive Oxygen Species; D013481:Superoxides; D003300:Copper; D006861:Hydrogen Peroxide; D002374:Catalase