1800MHz Microwave Induces p53 and p53-Mediated Caspase-3 Activation Leading to Cell Apoptosis In Vitro.
Recent studies have reported that exposure of mammalian cells to microwave radiation may have adverse effects such as induction of cell apoptosis. However, the molecular mechanisms underlying microwave induced mammalian cell apoptosis are not fully understood. Here, we report a novel mechanism: exposure to 1800MHz microwave radiation induces p53-dependent cell apoptosis through cytochrome c-mediated caspase-3 activation pathway. We first measured intensity of microwave radiation from several electronic devices with an irradiation detector. Mouse NIH/3T3 and human U-87 MG cells were then used as receivers of 1800MHz electromagnetic radiation (EMR) at a power density of 1209 mW/m2. Following EMR exposure, cells were analyzed for viability, intracellular reactive oxygen species (ROS) generation, DNA damage, p53 expression, and caspase-3 activity. Our analysis revealed that EMR exposure significantly decreased viability of NIH/3T3 and U-87 MG cells, and increased caspase-3 activity. ROS burst was observed at 6 h and 48 h in NIH/3T3 cells, while at 3 h in U-87 MG cells. Hoechst 33258 staining and in situ TUNEL assay detected that EMR exposure increased DNA damage, which was significantly restrained in the presence of N-acetyl-L-cysteine (NAC, an antioxidant). Moreover, EMR exposure increased the levels of p53 protein and p53 target gene expression, promoted cytochrome c release from mitochondrion, and increased caspase-3 activity. These events were inhibited by pretreatment with NAC, pifithrin-α (a p53 inhibitor) and caspase inhibitor. Collectively, our findings demonstrate, for the first time, that 1800MHz EMR induces apoptosis-related events such as ROS burst and more oxidative DNA damage, which in turn promote p53-dependent caspase-3 activation through release of cytochrome c from mitochondrion. These findings thus provide new insights into physiological mechanisms underlying microwave-induced cell apoptosis.
SCNU-ZJU Joint Research Center of Photonics, South China Academy of Advanced Optoelectronics, South China Normal University (SCNU), 510006 Guangzhou, China.|Department of Biology, South University of Science and Technology of China (SUSTC), Shenzhen 518055, China.
Fuqiang
F
Xing
SCNU-ZJU Joint Research Center of Photonics, South China Academy of Advanced Optoelectronics, South China Normal University (SCNU), 510006 Guangzhou, China.
Qiuqiang
Q
Zhan
Department of Biology, South University of Science and Technology of China (SUSTC), Shenzhen 518055, China.
Yiduo
Y
He
Department of Biology, South University of Science and Technology of China (SUSTC), Shenzhen 518055, China.
Jiesheng
J
Cui
SCNU-ZJU Joint Research Center of Photonics, South China Academy of Advanced Optoelectronics, South China Normal University (SCNU), 510006 Guangzhou, China.|Department of Electromagnetic Engineering, Royal Institute of Technology (KTH), 10044 Stockholm, Sweden.
Sailing
S
He
Department of Biology, South University of Science and Technology of China (SUSTC), Shenzhen 518055, China.
Guanyu
G
Wang
Bioelectromagnetics. 2006 May;27(4):295-306
16511873
Neurosci Lett. 2007 Jan 22;412(1):34-8
17187929
J Cell Physiol. 2014 Nov;229(11):1776-86
24676932
J Cell Biochem. 2002;84(3):447-54
11813250
Cell Death Differ. 2006 Sep;13(9):1423-33
16676004
Discov Med. 2010 Feb;9(45):145-52
20193641
Arch Toxicol. 2015 Apr;89(4):501-17
25618545
Radiat Environ Biophys. 2006 May;45(1):55-62
16552570
Radiat Res. 2006 Jan;165(1):88-94
16392966
Biochim Biophys Acta. 2003 Jun 17;1641(1):35-41
12788227
Bioelectromagnetics. 2012 Oct;33(7):604-11
22549623
Int J Med Sci. 2014 Mar 09;11(5):426-35
24688304
Mutat Res. 2005 Jun 6;583(2):178-83
15869902
Int Arch Occup Environ Health. 2003 Jul;76(6):431-6
12802592
Toxicol Lett. 2013 Mar 27;218(1):2-9
23333639
Electromagn Biol Med. 2015 Mar;34(1):85-92
24665905
Environ Health Perspect. 2005 Sep;113(9):1172-7
16140623
Proc Natl Acad Sci U S A. 2005 Mar 1;102(9):3225-9
15713802
FASEB J. 2005 Oct;19(12):1686-8
16116041
Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi. 2003 Oct;21(5):339-41
14761394
EMBO Rep. 2000 Sep;1(3):266-70
11256610
J Sleep Res. 2002 Dec;11(4):289-95
12464096
J Cell Physiol. 2007 Dec;213(3):759-67
17559061
J Cell Physiol. 2005 Aug;204(2):539-48
15754340
J Cell Physiol. 2000 Feb;182(2):171-81
10623880
Biochem Biophys Res Commun. 2010 Apr 30;395(2):190-5
20361931
J Cell Physiol. 1998 Nov;177(2):324-33
9766529
Cell Mol Neurobiol. 2012 Aug;32(6):1039-46
22395787
Am J Epidemiol. 2011 Aug 15;174(4):416-22
21712479
J Hepatol. 2011 Jan;54(1):164-72
20961644
Methods Mol Biol. 2008;414:13-21
18175808
Lancet Oncol. 2011 Jul;12(7):624-6
21845765
Apoptosis. 2000 Nov;5(5):415-8
11256882
Electromagn Biol Med. 2011 Dec;30(4):219-34
22047460
Int J Oncol. 2008 May;32(5):1097-103
18425337
Neuroreport. 2000 Mar 20;11(4):761-4
10757515
J Neurosci. 2013 Aug 14;33(33):13505-17
23946409
Nat Rev Mol Cell Biol. 2007 Apr;8(4):275-83
17380161
Brain Res. 2010 Sep 17;1352:255-64
20633539
Brain Res. 2010 Jan 22;1311:189-96
19879861
Bioelectromagnetics. 2003 Feb;24(2):82-90
12524674
Cancer Res. 2004 Apr 1;64(7):2350-6
15059885
Int Arch Occup Environ Health. 2008 May;81(6):755-67
18278508
J Membr Biol. 2013 Dec;246(12):869-75
24105626
Differentiation. 2002 May;70(2-3):120-9
12076339
J Cereb Blood Flow Metab. 2002 Jan;22(1):21-8
11807390
Bioelectromagnetics. 2004 Jul;25(5):324-8
15197754
Cell. 2005 Oct 7;123(1):49-63
16213212
J Biol Chem. 2003 Mar 7;278(10):8516-25
12496265
PLoS One. 2009 Jul 31;4(7):e6446
19649291