International Journal of Molecular Sciences (Nov 2011)

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

  • O-Yu Kwon,
  • Kweon Yu,
  • Seung-Whan Kim,
  • Tae-Won Goo,
  • Young Jin Choi,
  • Kyeong Ryong Lee,
  • Kisang Kwon,
  • Dae Young Hong

DOI
https://doi.org/10.3390/ijms12117652
Journal volume & issue
Vol. 12, no. 11
pp. 7652 – 7661

Abstract

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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.

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