Reactive oxygen species play a central role in hexavalent chromium-induced apoptosis in Hep3B cells without the functional roles of p53 and caspase-3.
OBJECTIVE
Hexavalent chromium [Cr(VI)] and its compounds, which have the extensive application in diverse industries including metallurgy, textile and electroplating, are known to be genotoxic and mutagenic to humans. Although it is supported by a large body of literatures that p53 and caspase-3 played key roles in Cr(VI)-induced cytotoxicity, it is clear that Cr(VI) could induce apoptosis either without activating caspase, or in a p53- independent manner.


METHODS
In the present study, by using Z-VAD-fmk to inhibit caspase-3 in p53-deficient Hep3B cells, we explored the effect of Cr(VI) on apoptosis induction and the related mechanisms when the functions of p53 and caspase were simultaneously blocked.


RESULTS
We found that Cr(VI) still induced DNA damage, mitochondrial injury, oxidative stress and apoptosis in Hep3B cells without the functional roles of p53 and caspase-3, and the mechanism study revealed that this was in a ROS-dependent manner since NAC co-treatment showed the protective effect against Cr(VI)-induced apoptosis.


CONCLUSIONS
Our research has disclosed the mechanism involved in Cr(VI)-induced cytotoxicity following the loss of p53 and caspase-3 functions and shed light on the importance of using antioxidants for primary and secondary prevention in Cr(VI) occupational exposure populations.
Department of Health Toxicology, School of Public Health, Central South University, Changsha, PR China.
Ming
M
Zeng
Fang
F
Xiao
Xiali
X
Zhong
Feng
F
Jin
Lan
L
Guan
An
A
Wang
Xinmin
X
Liu
Caigao
C
Zhong
D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism*; D002478:Cells, Cultured; D002857:Chromium / Q000633:toxicity*; D004785:Environmental Pollutants / Q000633:toxicity*; D006801:Humans; D017382:Reactive Oxygen Species / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D004785:Environmental Pollutants; D017382:Reactive Oxygen Species; D016159:Tumor Suppressor Protein p53; D002857:Chromium; C074702:chromium hexavalent ion; D053148:Caspase 3