Research Paper Volume 13, Issue 3 pp 4274—4290

The roles of PARP-1 and XPD and their potential interplay in repairing bupivacaine-induced neuron oxidative DNA damage

Wei Zhao1, *, , Zhongjie Liu1, *, , Jiaming Luo1, , Changqing Ma1, , Luying Lai1, , Zhengyuan Xia2,3, , Shiyuan Xu1, ,

  • 1 Department of Anesthesiology, ZhuJiang Hospital, Southern Medical University, Guangdong Province, China
  • 2 State Key Laboratory of Pharmaceutical Biotechnology and Department of Anesthesiology, University of Hong Kong, Hong Kong
  • 3 Department of Anesthesiology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China
* Equal contribution

Received: January 13, 2020       Accepted: November 17, 2020       Published: January 20, 2021
How to Cite

Copyright: © 2021 Zhao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Bupivacaine has been widely used in clinical Anesthesia, but its neurotoxicity has been frequently reported, implicating cellular oxidative DNA damage as the major underlying mechanism. However, the mechanism underlying bupivacaine-induced oxidative DNA damage is unknown. We, thus, exposed SH-SY5Y cells to 1.5mM bupivacaine to induce neurotoxicity. Then, iTRAQ proteomic analysis was used to explore the repair of neuronal oxidative DNA damage. By analyzing the STRING version 11.0 database, the bioinformatics relationship between key repair enzymes was tracked. Subsequently, immunofluorescence co-localization and immunoprecipitation were used to investigate the interaction between key repair enzymes. The iTRAQ showed that Poly [ADP-ribose] polymerase 1 (PARP-1) from the base excision repair pathway participated closely in the repair of oxidative DNA damage induced by bupivacaine, and inhibition of PARP-1 expression significantly aggravated bupivacaine-induced DNA damage and apoptosis. Interestingly, this study showed that there were interactions and co-expression between PARP-1 and XPD (xeroderma pigmentosum D), another key protein of the nucleic acid excision repair pathway. After inhibiting XPD, PARP-1 expression was significantly reduced. However, simultaneous inhibition of both XPD and PARP-1 did not further increase DNA damage. It is concluded that PARP-1 may repair bupivacaine-induced oxidative DNA damage through XPD-mediated interactions.


LA: local anesthetics; Bup: Bupivacaine; iTRAQ: Isobaric tagging for relative and absolute protein quantification; ROS: reactive oxygen species; DHE: dihydroethidium; BER: base excision repair; NER: nucleotide excision repair; XPD: xeroderma pigmentosum D; PARP-1: Poly [ADP-ribose] polymerase 1; pADPr: Poly (ADP-ribose) Polymer; Bup-vs-C: comparison of bupivacaine groups and control group.