Mechanical stimulation suppresses phosphorylation of eIF2alpha and PERK-mediated responses to stress to the endoplasmic reticulum.
Cellular perturbations such as stress to the endoplasmic reticulum induce an integrated stress response, which activates phosphorylation of eIF2alpha and leads to alleviation of cellular injury or apoptosis. This study investigated the role of mechanical stimulation in the regulation of eIF2alpha and cell death. Mechanical stimulation was applied to mouse ulnae, MC3T3 cells, and mesenchymal stem cells. The results demonstrate that mechanical stimulation reduces phosphorylation of eIF2alpha through inactivation of Perk. Furthermore, flow pre-treatment reduces thapsigargin-induced cell mortality through suppression of phosphorylation of Perk. However, H(2)O(2)-driven cell mortality, which is not mediated by Perk, is not suppressed by mechanical stimulation. Taken together, our observations suggest a pro-survival role of mechanical stimulation in Perk-mediated stress responses.
Hirasawa
Hideyuki
H
Department of Biomedical Engineering, Indiana University-Purdue University Indianapolis, Indianapolis, IN 46202, USA.
Jiang
Chang
C
Zhang
Ping
P
Yang
Feng-Chun
FC
Yokota
Hiroki
H
D016475:3T3 Cells; D051700:Activating Transcription Factor 3 / Q000235:genetics; D051701:Activating Transcription Factor 4 / Q000235:genetics; D051702:Activating Transcription Factor 6 / Q000235:genetics; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D015852:Eukaryotic Initiation Factor-2 / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006861:Hydrogen Peroxide / Q000494:pharmacology; D015151:Immunoblotting; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D010766:Phosphorylation / Q000187:drug effects; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013314:Stress, Mechanical; D019284:Thapsigargin / Q000494:pharmacology; D051742:Transcription Factor CHOP / Q000235:genetics; D014415:Tunicamycin / Q000494:pharmacology; D019892:eIF-2 Kinase / Q000235:genetics / Q000378:metabolism*
D051700:Activating Transcription Factor 3; D051701:Activating Transcription Factor 4; D051702:Activating Transcription Factor 6; D015852:Eukaryotic Initiation Factor-2; D006861:Hydrogen Peroxide; D019284:Thapsigargin; D051742:Transcription Factor CHOP; D014415:Tunicamycin; D019892:eIF-2 Kinase; C103002:Atf3 protein, mouse; C081452:Atf4 protein, mouse; C497112:Atf6 protein, mouse; C497250:Ddit3 protein, mouse