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Int. J. Mol. Sci. 2011, 12(11), 7652-7661; doi:10.3390/ijms12117652
Article

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

1,†
,
2,†
,
1
,
2
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3
,
4
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5,*  and 2,*
1 Department of Emergency Medicine, Konkuk University Medical Center, Seoul 143-729, Korea 2 Department of Anatomy, Chungnam National University, Taejon 301-747, Korea 3 Department of Agricultural Biology, National Academy of Agricultural Science, RDA, Suwon 441-100, Korea 4 Korea Research Institute of Bioscience and Biotechnology, Taejon 305-806, Korea 5 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 / Revised: 25 October 2011 / Accepted: 26 October 2011 / Published: 8 November 2011
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
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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 lidocaine; endoplasmic reticulum (ER) stress; ER chaperone; ER stress sensor; apoptosis
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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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.

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