The relationship between p53/p21/Rb and MAPK signaling pathways in human endometrium-derived stem cells under oxidative stress
- Autores: Deryabin P.1, Borodkina A.1, Nikolsky N.1, Burova E.1
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Afiliações:
- Institute of Cytology
- Edição: Volume 10, Nº 3 (2016)
- Páginas: 185-193
- Seção: Article
- URL: https://journals.rcsi.science/1990-519X/article/view/212080
- DOI: https://doi.org/10.1134/S1990519X16030056
- ID: 212080
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Resumo
Human endometrium-derived mesenchymal stem cells (hMESC) under the sublethal oxidative stress induced by H2O2 activate both the p53/p21/Rb and p38/MAPKAPK-2 pathways that are responsible for the induction of hMESC premature senescence (Borodkina et al., 2014). However, the interrelations between the p53/p21/Rb and MAPK signaling pathways, including ERK1/2, p38, and JNK, remain yet unexplored. Here, we used the specific inhibitors—pifithrin-α (PFT), U0126, SB203580, and SP600125 to “switch off” one of the proteins in these cascades and to evaluate the functional status alterations of the rest of the proteins. Each MAPK suppression significantly increased the p53 phosphorylation level, as well as p21 protein expression followed by Rb hypophosphorylation. On the other hand, PFT-induced p53 inhibition enhanced mostly the ERK1/2 activation rather than p38 and JNK. These results suggest the existence of a reciprocal negative regulation between p53- and MAPK-dependent signaling pathways. By analyzing the possible interactions among the members of the MAPK family, we showed that p38 and JNK can function as ERK antagonists: JNK is able to activate ERK, while p38 may block ERK activation. Together, these results demonstrate the existence of complex links between different signaling cascades in stressed hMESC, implicating ERK, p38, and JNK in regulation of premature senescence via the p53/p21/Rb pathway.
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Sobre autores
P. Deryabin
Institute of Cytology
Email: lenbur87@mail.ru
Rússia, St. Petersburg, 194064
A. Borodkina
Institute of Cytology
Email: lenbur87@mail.ru
Rússia, St. Petersburg, 194064
N. Nikolsky
Institute of Cytology
Email: lenbur87@mail.ru
Rússia, St. Petersburg, 194064
E. Burova
Institute of Cytology
Autor responsável pela correspondência
Email: lenbur87@mail.ru
Rússia, St. Petersburg, 194064