title: Protective induction of Hsp70 in heat-stressed primary myoblasts: Involvement of MAPKs.
abstract: The involvement of extracellular signal-regulated kinases 1 and 2 (ERK1,2), stress kinase p38 and c-Jun NH2 -terminal kinases 1 and 2 (JNK1,2) on Hsp70-upregulation following mild heat shock, and resulting cell protection, was studied on rabbit primary myoblasts. Cells subjected to heat stress (42°C; 60 min) showed a significantly enhanced amount of heat-shock-induced protein 70 (Hsp70), correlating with sustained phosphorylation of MAP kinases ERK1,2, inhibition of p38 and JNK1,2 activation. Induced Hsp70 did not autocrinally suppress activation of transcription factor c-Jun, suggesting involvement of the latter in the protection of myoblasts following heat shock. The inhibition of stress kinases p38, JNK1,2, and MEK1,2 by SP600125, SB203580, and UO126, respectively, established the involvement of JNK1,2 and p38 as upstream, and ERK1,2 as downstream targets of Hsp70 induction. Moreover, the effect of the MEK1,2 inhibitor UO126 revealed a new pathway of c-Jun activation by ERK1,2 in myogenic heat-stressed stem cells. The presented data show that transient activation of JNK1, JNK2, and p38 is necessary for Hsp70 induction and ensuing cell protection. In conclusion, affecting myogenic stem cell protective mechanisms might be a useful strategy in improving stem cell survival and their expanded application in therapy.
authors.affiliation: Department of Stem Cell Biology, State Research Institute Centre for Innovative Medicine, LT01102, Vilnius, Lithuania. daibironai@gmail.com
authors.forename: Daiva
authors.initials: D
authors.lastname: Bironaite
authors.forename: Ulf
authors.initials: U
authors.lastname: Brunk
authors.forename: Algirdas
authors.initials: A
authors.lastname: Venalis
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D015153:Blotting, Western; D002470:Cell Survival / Q000235:genetics / Q000502:physiology; D002478:Cells, Cultured; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D007150:Immunohistochemistry; D020935:MAP Kinase Signaling System / Q000235:genetics / Q000502:physiology; D032446:Myoblasts / Q000166:cytology* / Q000378:metabolism*; D011817:Rabbits; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism
chemical_list: D018840:HSP70 Heat-Shock Proteins
keywords: HEAT STRESS; HSP; MAPK; SIGNALING; STEM CELLS