Lidocaine Induces Endoplasmic Reticulum Stress-Associated Apoptosis in Vitro and in Vivo

International Journal of Molecular Sciences

Dae Young Hong¹  Kisang Kwon³  Kyeong Ryong Lee¹  Young Jin Choi³  Tae-Won Goo⁵  Kweon Yu⁴  Seung-Whan Kim² 

[1] Department of Emergency Medicine, Konkuk University Medical Center, Seoul 143-729, Korea; E-Mails:;Department of Emergency Medicine, Chungnam National University Hospital, Taejon 301-721, Korea;Department of Anatomy, Chungnam National University, Taejon 301-747, Korea; E-Mails:;Korea Research Institute of Bioscience and Biotechnology, Taejon 305-806, Korea; E-Mail:;Department of Agricultural Biology, National Academy of Agricultural Science, RDA, Suwon 441-100, Korea; E-Mail:

关键词: lidocaine;    endoplasmic reticulum (ER) stress;    ER chaperone;    ER stress sensor;    apoptosis;   

DOI  :  10.3390/ijms12117652

来源: mdpi

【 摘 要 】

We demonstrated that upregulation of both gene expression of endoplasmic reticulum (ER) stress chaperones (BiP, calnexin, calreticulin, and PDI) and ER stress sensors (ATF6, IRE1 and PERK) was induced by lidocaine, a local anesthetic, in PC12 cells. In addition to gene regulation, lidocaine also induced typical ER stress phenomena such as ART6 proteolytic cleavage, eIF2 alpha phosphorylation, and XBP1 mRNA splicing. In in vivo experiments, while lidocaine downregulated gene expression of antiapoptotic factors (Bcl-2 and Bcl-xl), pro-apoptotic factor (Bak and Bax) gene expression was upregulated. Furthermore, lidocaine induced apoptosis, as measured histochemically, and upregulated PARP1, a DNA damage repair enzyme. These results are the first to show that lidocaine induces apoptosis through ER stress in vitro and in vivo.

【 授权许可】

CC BY   
© 2011 by the authors; licensee MDPI, Basel, Switzerland.