2012
Volume 12, Number 4, pp. 155–157
Action of thyroid hormones and fisetin on the activation of ERK and Akt protein kinases in PC12 cells
T. Barbakadze,1, 2 N. Natsvlishvili1, 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 phosphorylation of two protein kinases, Akt and ERK, via the integrinv3 receptor of the thyroid hormones (TH) were examined in proliferating and differentiating PC12 cells. Differentiation of PC12 cells was induced by the flavonoid fisetin and the phosphorylated forms of two Ras-dependent downstream protein kinases, ERK and Akt were analysed by Western blotting. We have found that in proliferating conditions T4 increases the phosphorylation of ERK, which is inhibited by a deaminated analogue of T4, tetraiodothyroacetic acid (TETRAC). In differentiating PC12 cells and in the presence of fisetin, TETRAC does not change the T4-induced phosphorylation of ERK. The phosphorylated form of Akt (p-Akt) was increased in the presence of both T3 and T4; however, TETRAC does not act on the phosphorylation of Akt in proliferating PC12 cells. In differentiated cells, the content of p-Akt under the action of T3 is also increased and this elevation is sensitive to TETRAC. These results imply that in the proliferating PC12 cells T4 operates through the integrin v3 receptor of thyroid hormones, whereas in the differentiating PC12 cells the action of T3 dominates. We infer that fisetin can change the sensitivity of PC12 cells to thyroid hormones by switching the non-genomic integrin-dependent action of T4 into the genomic action of T3.
Keywords: cell differentiation, fisetin, thyroid hormones, p-Akt, PC12 cells, p-ERK