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.

Details

Title
Lidocaine Induces Endoplasmic Reticulum Stress-Associated Apoptosis in Vitro and in Vivo
Author
Hong, Dae Young; Kwon, Kisang; Lee, Kyeong Ryong; Choi, Young Jin; Goo, Tae-Won; Yu, Kweon; Kim, Seung-Whan; Kwon, O-Yu
Pages
7652-7661
Publication year
2011
Publication date
2011
Publisher
MDPI AG
ISSN
16616596
e-ISSN
14220067
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
1526141695
Copyright
Copyright MDPI AG 2011