Lidocaine induces endoplasmic reticulum stress-associated apoptosis in Vitro and in Vivo

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Title
Lidocaine induces endoplasmic reticulum stress-associated apoptosis in Vitro and in Vivo
Author(s)
D Y Hong; K Kwon; K R Lee; Y J Choi; T W Goo; Kweon Yu; S W Kim; O Y Kwon
Bibliographic Citation
International Journal of Molecular Sciences, vol. 12, no. 11, pp. 7652-7661
Publication Year
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.
Keyword
ApoptosisEndoplasmic reticulum (ER) stressER chaperoneER stress sensorLidocaine
ISSN
1422-0067
Publisher
MDPI
DOI
http://dx.doi.org/10.3390/ijms12117652
Type
Article
Appears in Collections:
Division of Biomedical Research > Disease Target Structure Research Center > 1. Journal Articles
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