Protection of myogenic stem cells by heat shock-induced Hsp70. Involvement of MAPKs.

Daiva Bironaite, State Research Institute Centre for Innovative Medicine, Vilnius, Lithuania

Heat shock proteins (Hsp(s)), particularly inducible Hsp70 family members (iHsp70, Hsp72 or Hsp70), are conserved chaperones, protecting eukaryotic cells from a variety of stresses. We investigated involvement of MAPKs particularly an extra-cellular signal-regulated kinases 1 and 2 (ERK1,2), stress kinases p38 and c-Jun NH2-terminal kinases 1 and 2 (JNK1,2) in upregulation of heat shock-induced Hsp70 (iHsp70) in mesenchymal origin myogenic stem cells. Myogenic stem cells subjected to heat stress showed significant HSF-1 and iHsp70 upregulation. The upregulation of iHsp70 correlated with sustained phosphorylation of MAP kinases ERK1,2, whereas activation of p38 and JNK1,2 was significantly inhibited. However, the exposure of cells to specific MAPKs inhibitors revealed JNK1,2 and p38 being an upstream, and ERK1,2 a downstream targets in Hsp70 induction. iHsp70 did not autocrinelly suppressed activation and total amount of transcription factor c-Jun, suggesting it’s involvement in protection of myogenic stem sell following heat shock. Our data also revealed that translocation of MAPK to nucleus depended on the intensity of stress and duration of recover period. In conclusion, our data show that pro-apoptotic stress kinases JNK1,2 and p38 initially participate in iHsp70 induction and stem cell protection mechanism against various stresses. Investigation and regulation of signaling pathways protecting myogenic stem cell might be a useful strategy improving survival of transplanted stem cell and expanding their application in therapy.