2012
Volume 12, Number 4, pp. 152–154
Integrin thyroid hormone receptor and fisetin regulate the nuclear translocation of FoxO6 transcription factor and c-Rel in PC12 cells
N. Natsvlishvili,1, 2 T. Barbakadze1, 2 and D. Mikeladze1, 2
1 Ilia State University, 3/5 K. Cholokhashvili St, 0162 Tbilisi, Georgia
2 I. Beritashvili Centre of Experimental Biomedicine, 14 Gotua St, 0160 Tbilisi, Georgia
The effects of thyroid hormones (T3 and T4) on the integrin 3v receptor (THYR) were examined in proliferating and differentiating PC12 cells. Differentiation of PC12 cells was induced by fisetin and the levels of FoxO6 and c-Rel transcription factors were analysed in nuclear fractions by Western blotting and enhancer-binding activity, respectively. We have found that fisetin increases nuclear translocation of FoxO6, and thyroid hormones do not change the levels of FoxO6. However, the deaminated analogue of T4, tetraiodothyroacetic acid (TETRAC), an antagonist of THYR, greatly decreases the content of FoxO6 in nuclei. Furthermore, we have shown that inhibition of THYR in nondifferentiated cells by TETRAC blocks c-Rel activity, whereas inhibition of the receptor in differentiated cells leads to the activation of c-Rel. These data indicate that some of the physiological benefits of fisetin are induced via THYR through blocking of the cRel/NF-kB pathway and by activation of FoxO6 transcription. Our data further suggest that THYR may be involved in the transition of PC cells to a differentiated state. During this transition the sensitivity of THYR is changed from T3 towards T4.
Keywords: cell differentiation, fisetin, PC12 cells, thyroid hormones