The role of p38 MAP-kinase in stress-induced senescence of human endometrium-derived mesenchymal stem cells

Abstract

Our recent findings demonstrate that human endometrium-derived mesenchymal stem cells (hMESCs) respond to sublethal oxidative stress by stress-induced premature senescence via the АТМ/Chk2/p53/p21/Rb pathway. Application of SB203580 (SB) inhibitor suggested p38 MAP-kinase involvement in the senescence progression. However, there are several disadvantages concerning this inhibitor: (1) SB is toxic and hardly suitable for in vivo experiments and (2) poor kinase selectivity profile of SB complicates interpretation of the obtained data. Here, to confirm the involvement of p38 in H₂O₂-induced hMESCs senescence, we applied another highly specific p38 inhibitor, BIRB796 (BIRB). In the presence of BIRB, the cell size decreased, the level of reactive oxygen species reduced, proliferation partially resumed, and Rb phosphorylation level increased in comparison to H₂O₂-treated hMESCs. Summarizing these results, we can postulate p38 involvement in H₂O₂-induced senescence of hMESCs and suggest p38 inhibition as a promising approach in prevention of premature senescence.