Vol. 45 (2003), ¹ 5, p. 478-487
DEPENDENCE OF EGF RECEPTOR AND STAT FACTOR ACTIVATION ON RED-OX STATE OF A431 CELLS

I. V. Gonchar, E. B. Burova, V. N. Dorosh, I. A. Gamaley, N. N. Nikolsky

Institute of Cytology RAS, St. Petersburg;
e-mail: burova_e@mail.cyt.spb.rssi.ru

Reactive oxygen species (ROS) were established to play an important role in cellular signaling as second messengers by integrating different pathways. Recently, we showed that EGF initiated a rapid tyrosine phosphorylation of both EGF-receptor and STAT factors with simultaneous increase in the intracellular ROS level. Now, we have investigated the effect of intracellular red-ox state on EOF- and H2O2-induced activation of EGF receptor, STAT1 and STATS. We demonstrated that the pretreatment of A431 cells with antioxidant N-acetyl-L-cysteine (NAC) partly reduced the level of EGF-induced phosphorylation of proteins under investigation. Besides, H2O2-induced activation of EGF receptor, and STAT factors was fully prevented by NAC pretreatment. The inhibition of ROS generation by DPI declined EGF-dependent activation of EGF receptor and STAT factors to basal level. Our results demonstrate the essential role of cellular red-ox status in the modulation of EGF-mediated activation of receptor and STAT factors. We have postulated that EGF-induced ROS generation is a very important initial event promoting physiological activation of EGF receptor and subsequent STAT factor activation.

Key words:  reactive oxygen species, transcription factors STAT, antioxidants, epidermal growth factor


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