Mechanical stimulation suppresses phosphorylation of eIF2α and PERK-mediated responses to stress to the endoplasmic reticulum

Hirasawa, Hideyuki; Jiang, Chang; Zhang, Ping; Yang, Feng-Chun; Yokota, Hiroki

doi:10.1016/j.febslet.2009.12.028

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Volume 584, Issue 4 , Pages 745-752, 19 February 2010

Mechanical stimulation suppresses phosphorylation of eIF2α and PERK-mediated responses to stress to the endoplasmic reticulum

Edited by Robert Barouki

Hideyuki Hirasawa
- Department of Biomedical Engineering, Indiana University – Purdue University Indianapolis, Indianapolis, IN 46202, United States
- These two authors contributed equally to the study.
Chang Jiang
- Department of Biomedical Engineering, Indiana University – Purdue University Indianapolis, Indianapolis, IN 46202, United States
- These two authors contributed equally to the study.
Ping Zhang
- Department of Biomedical Engineering, Indiana University – Purdue University Indianapolis, Indianapolis, IN 46202, United States
- Department of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, IN 46202, United States
Feng-Chun Yang
- Department of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, IN 46202, United States
- Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN 46202, United States
- Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202, United States
Hiroki Yokota
- Department of Biomedical Engineering, Indiana University – Purdue University Indianapolis, Indianapolis, IN 46202, United States
- Department of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, IN 46202, United States
- Corresponding author. Address: Department of Biomedical Engineering, Indiana University – Purdue University Indianapolis, 723 West Michigan Street, Indianapolis, IN 46202, United States. Fax: +1 317 278 2455.

Received 2 October 2009; received in revised form 4 December 2009; accepted 16 December 2009. published online 22 December 2009.

Abstract

Cellular perturbations such as stress to the endoplasmic reticulum induce an integrated stress response, which activates phosphorylation of eIF2α and leads to alleviation of cellular injury or apoptosis. This study investigated the role of mechanical stimulation in the regulation of eIF2α 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 eIF2α through inactivation of Perk. Furthermore, flow pre-treatment reduces thapsigargin-induced cell mortality through suppression of phosphorylation of Perk. However, H₂O₂-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.

Keywords: Ulna, Osteoblast, MSC, Mechanical stimulation, Endoplasmic reticulum, Perk