Electromagnetic fields at mobile phone frequency induce apoptosis and inactivation of the multi-chaperone complex in human epidermoid cancer cells

被引:90
作者
Caraglia, M
Marra, M
Mancinelli, F
D'Ambrosio, G
Massa, R
Giordano, A
Budillon, A
Abbruzzese, A
Bismuto, E
机构
[1] Seconda Univ Napoli, Dipartimento Biochim & Biofis, I-80138 Naples, Italy
[2] Fdn G Pascale, Natl Inst Tumours, Expt Pharmacol Unit, Naples, Italy
[3] Univ Naples Federico 2, ICEmB, Dept Elect & Telecommun Engn, Naples, Italy
[4] Temple Univ, Coll Sci & Technol, Ctr Biotechnol, Sbarro Inst Canc Res & Mol Med, Philadelphia, PA 19122 USA
[5] Univ Siena, Dept Human Pathol & Oncol, I-53100 Siena, Italy
关键词
D O I
10.1002/jcp.20327
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The exposure to non-thermal microwave electromagnetic field (MW-EMF) at 1.95 MHz, a frequency used in mobile communication, affects the refolding kinetics of eukaryotic proteins (Mancinelli et al., 2004). On these basis we have evaluated the in vivo effect of MW-EMF in human epidermoid cancer KB cells. We have found that MW-EMF induces time-dependent apoptosis (45% after 3 h) that is paralleled by an about 2.5-fold decrease of the expression of ras and Raf-1 and of the activity of ras and Erk-1/2. Although also the expression of Akt was reduced its activity was unchanged likely as a consequence of the increased expression of its upstream activator PI3K. In the same experimental conditions an about 2.5-fold increase of the ubiquitination of ras and Raf-1 was also found and the addition for 12 h of proteasome inhibitor lactacystin at 10 mu M caused an accumulation of the ubiquitinated isoforms of ras and Raf-1 and counteracted the effects of MW-EMF on ras and Raf-1 expression suggesting an increased proteasome-dependent degradation induced by MW-EMF. The exposure of KB cells to MW-EMF induced a differential activation of stress-dependent pathway with an increase of JNK-1 activity and HSP70 and 27 expression and with a reduction of p38 kinase activity and HSP90 expression. The overexpression of HSP90 induced by transfection of KB cells with a plasmid encoding for the factor completely antagonized the apoptosis and the inactivation of the ras -> Erk-dependent survival signal induced by MW-EMF. Conversely, the inhibition of Erk activity induced by 12 h exposure to 10 mM Mek-1 inhibitor UO126 antagonized the effects induced by HSP90 transfection on apoptosis caused by MW-EMF. In conclusion, these results demonstrate for the first time that MW-EMF induces apoptosis through the inactivation of the ras, Erk survival signaling due to enhanced degradation of ras and Raf-1 determined by decreased expression of HSP90 and the consequent increase of proteasome dependent degradation. J. Cell. Physiol. 204: 539-548, 2005. (c) 2005 Wiley-Liss, Inc.
引用
收藏
页码:539 / 548
页数:10
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