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Lidocaine Induces Endoplasmic Reticulum Stress-Associated Apoptosis in Vitro and in Vivo
Department of Emergency Medicine, Konkuk University Medical Center, Seoul 143-729, Korea
Department of Anatomy, Chungnam National University, Taejon 301-747, Korea
Department of Agricultural Biology, National Academy of Agricultural Science, RDA, Suwon 441-100, Korea
Korea Research Institute of Bioscience and Biotechnology, Taejon 305-806, Korea
Department of Emergency Medicine, Chungnam National University Hospital, Taejon 301-721, Korea
These authors contributed equally to this work.
* Authors to whom correspondence should be addressed.
Received: 11 October 2011; in revised form: 25 October 2011 / Accepted: 26 October 2011 / Published: 8 November 2011
Abstract: 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 anti-apoptotic 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.
Keywords: lidocaine; endoplasmic reticulum (ER) stress; ER chaperone; ER stress sensor; apoptosis
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Hong, D.Y.; Kwon, K.; Lee, K.R.; Choi, Y.J.; Goo, T.-W.; Yu, K.; Kim, S.-W.; Kwon, O.-Y. Lidocaine Induces Endoplasmic Reticulum Stress-Associated Apoptosis in Vitro and in Vivo. Int. J. Mol. Sci. 2011, 12, 7652-7661.
Hong DY, Kwon K, Lee KR, Choi YJ, Goo T-W, Yu K, Kim S-W, Kwon O-Y. Lidocaine Induces Endoplasmic Reticulum Stress-Associated Apoptosis in Vitro and in Vivo. International Journal of Molecular Sciences. 2011; 12(11):7652-7661.
Hong, Dae Young; Kwon, Kisang; Lee, Kyeong Ryong; Choi, Young Jin; Goo, Tae-Won; Yu, Kweon; Kim, Seung-Whan; Kwon, O-Yu. 2011. "Lidocaine Induces Endoplasmic Reticulum Stress-Associated Apoptosis in Vitro and in Vivo." Int. J. Mol. Sci. 12, no. 11: 7652-7661.