NADPH-Oxidase 2 Promotes Autophagy in Spinal Neurons During the Development of Morphine Tolerance

Overview

Journal Neurochem Res

Specialties Chemistry
Neurology

Date 2021 May 19

PMID 34008119

Citations 3

Authors

Xuyang Xiao

Huilian Bu

Zhisong Li

Zheng Li

Qian Bai

Zhitao Wang

Lin Yan

Daiqiang Liu

Xiaoling Peng

Xiaoqian Jia

Feng Gao

Affiliations

Soon will be listed here.

Abstract

Repeated morphine administration results in analgesic tolerance. However, the underlying mechanism of morphine analgesic tolerance remains unclear. NADPH-oxidase 2 (NOX2) is the first discovered NADPH oxidase, which mainly functions to produce reactive oxygen species. Its specific role in morphine tolerance has not been fully investigated. In this work, we found that chronic morphine administration significantly increased the expression of NOX2 in spinal cord. Pretreatment of NOX2 inhibitor blocked the upregulation of NOX2 and autophagy markers, including LC3B and P62, and consequently the development of morphine tolerance. NOX2 and LC3B were both colocalized with NeuN in spinal dorsal horn in morphine-tolerant rats. Our results suggest that the increased autophagy activity in spinal neurons promoted by NOX2 activation contributes to the development of morphine tolerance. NOX2 may be considered as a new therapeutic target for morphine tolerance.

Citing Articles

Multi-omic analysis of a mucolipidosis II neuronal cell model uncovers involvement of pathways related to neurodegeneration and drug metabolism.

Badenetti L, Yu S, Colonna M, Hull R, Bethard J, Ball L Mol Genet Metab. 2024; 143(3):108596.

PMID: 39461112 PMC: 11569414. DOI: 10.1016/j.ymgme.2024.108596.

Permissive lung neutrophils facilitate tuberculosis immunopathogenesis in male phagocyte NADPH oxidase-deficient mice.

Choi E, Choi H, Kwon K, Kim H, Ryu J, Hong J PLoS Pathog. 2024; 20(8):e1012500.

PMID: 39178329 PMC: 11376565. DOI: 10.1371/journal.ppat.1012500.

NADPH Oxidases in Pain Processing.

Kallenborn-Gerhardt W, Schroder K, Schmidtko A Antioxidants (Basel). 2022; 11(6).

PMID: 35740059 PMC: 9219759. DOI: 10.3390/antiox11061162.

References

Hayashi Y, Koga Y, Zhang X, Peters C, Yanagawa Y, Wu Z . Autophagy in superficial spinal dorsal horn accelerates the cathepsin B-dependent morphine antinociceptive tolerance. Neuroscience. 2014; 275:384-94. DOI: 10.1016/j.neuroscience.2014.06.037. View

Inturrisi C . Clinical pharmacology of opioids for pain. Clin J Pain. 2002; 18(4 Suppl):S3-13. DOI: 10.1097/00002508-200207001-00002. View

Suzuki M, Narita M, Niikura K, Nakamura A, Miyatake M, Yajima Y . mu-Opioid receptor internalization-dependent and -independent mechanisms of the development of tolerance to mu-opioid receptor agonists: Comparison between etorphine and morphine. Neuroscience. 2006; 138(2):609-19. DOI: 10.1016/j.neuroscience.2005.11.046. View

Martini L, Whistler J . The role of mu opioid receptor desensitization and endocytosis in morphine tolerance and dependence. Curr Opin Neurobiol. 2007; 17(5):556-64. DOI: 10.1016/j.conb.2007.10.004. View

Szentirmay A, Kiraly K, Lenkey N, Lacko E, Al-Khrasani M, Friedmann T . Spinal interaction between the highly selective μ agonist DAMGO and several δ opioid receptor ligands in naive and morphine-tolerant mice. Brain Res Bull. 2012; 90:66-71. DOI: 10.1016/j.brainresbull.2012.09.006. View

Ma W, Zheng W, Powell K, Jhamandas K, Quirion R . Chronic morphine exposure increases the phosphorylation of MAP kinases and the transcription factor CREB in dorsal root ganglion neurons: an in vitro and in vivo study. Eur J Neurosci. 2001; 14(7):1091-104. DOI: 10.1046/j.0953-816x.2001.01731.x. View

Guo G, Gao F . CXCR3: latest evidence for the involvement of chemokine signaling in bone cancer pain. Exp Neurol. 2015; 265:176-9. DOI: 10.1016/j.expneurol.2015.02.003. View

Guo G, Peng Y, Xiong B, Liu D, Bu H, Tian X . Involvement of chemokine CXCL11 in the development of morphine tolerance in rats with cancer-induced bone pain. J Neurochem. 2016; 141(4):553-564. DOI: 10.1111/jnc.13919. View

Wang W, Peng Y, Yang H, Bu H, Guo G, Liu D . Potential role of CXCL10/CXCR3 signaling in the development of morphine tolerance in periaqueductal gray. Neuropeptides. 2017; 65:120-127. DOI: 10.1016/j.npep.2017.07.004. View

10.

Liu D, Zhou Y, Peng Y, Su P, Li Z, Xu Q . Endoplasmic Reticulum Stress in Spinal Cord Contributes to the Development of Morphine Tolerance. Front Mol Neurosci. 2018; 11:72. PMC: 5845556. DOI: 10.3389/fnmol.2018.00072. View

11.

Thellung S, Scoti B, Corsaro A, Villa V, Nizzari M, Gagliani M . Pharmacological activation of autophagy favors the clearing of intracellular aggregates of misfolded prion protein peptide to prevent neuronal death. Cell Death Dis. 2018; 9(2):166. PMC: 5833808. DOI: 10.1038/s41419-017-0252-8. View

12.

Glick D, Barth S, Macleod K . Autophagy: cellular and molecular mechanisms. J Pathol. 2010; 221(1):3-12. PMC: 2990190. DOI: 10.1002/path.2697. View

13.

Henriksen E, Diamond-Stanic M, Marchionne E . Oxidative stress and the etiology of insulin resistance and type 2 diabetes. Free Radic Biol Med. 2010; 51(5):993-9. PMC: 3071882. DOI: 10.1016/j.freeradbiomed.2010.12.005. View

14.

Chuang Y . Mitochondrial dysfunction and oxidative stress in seizure-induced neuronal cell death. Acta Neurol Taiwan. 2010; 19(1):3-15. View

15.

Wu D, Cederbaum A . Inhibition of autophagy promotes CYP2E1-dependent toxicity in HepG2 cells via elevated oxidative stress, mitochondria dysfunction and activation of p38 and JNK MAPK. Redox Biol. 2013; 1:552-65. PMC: 3836279. DOI: 10.1016/j.redox.2013.10.008. View

16.

Scherz-Shouval R, Elazar Z . ROS, mitochondria and the regulation of autophagy. Trends Cell Biol. 2007; 17(9):422-7. DOI: 10.1016/j.tcb.2007.07.009. View

17.

Bedard K, Krause K . The NOX family of ROS-generating NADPH oxidases: physiology and pathophysiology. Physiol Rev. 2007; 87(1):245-313. DOI: 10.1152/physrev.00044.2005. View

18.

Doyle T, Esposito E, Bryant L, Cuzzocrea S, Salvemini D . NADPH-oxidase 2 activation promotes opioid-induced antinociceptive tolerance in mice. Neuroscience. 2013; 241:1-9. PMC: 4184413. DOI: 10.1016/j.neuroscience.2013.02.042. View

19.

Zorov D, Juhaszova M, Sollott S . Mitochondrial reactive oxygen species (ROS) and ROS-induced ROS release. Physiol Rev. 2014; 94(3):909-50. PMC: 4101632. DOI: 10.1152/physrev.00026.2013. View

20.

MacFarlane P, Mitchell G . Episodic spinal serotonin receptor activation elicits long-lasting phrenic motor facilitation by an NADPH oxidase-dependent mechanism. J Physiol. 2009; 587(Pt 22):5469-81. PMC: 2793877. DOI: 10.1113/jphysiol.2009.176982. View