Skip to main content
Log in

Induction of DJ-1 protects neuronal cells from isoflurane induced neurotoxicity

Metabolic Brain Disease Aims and scope Submit manuscript

Abstract

Oxidative stress, mitochondrial dysfunction and neuronal apoptosis are thought to be major contributors of Isoflurane toxicity. However, the underlying mechanisms remain largely to be determined. DJ-1, a protein that is involved in the response to various kinds of stress, has shown its neuroprotective effects. Whether DJ-1 has a neuroprotective effect against isoflurane-induced neurotoxocity is still unknown. In this study, we found that expression of DJ-1 is elevated in response to isoflurane treatment in human SH-SY5Y neuroblastoma cells. In order to clarify whether DJ-1 plays a potential role in isoflurane neurotoxicity or as a compensatory response for survival, we investigated the effects of DJ-1 silencing in isoflurane neurotoxicity. Our findings indicate that knockdown of DJ-1 promotes isoflurane-induced oxidative stress and mitochondrial dysfunction. Importantly, DJ-1 silencing was found to exacerbate isoflurane- induced apoptosis through modulation of mitochondria-dependent apoptosis pathways, thereby suggesting that induction of DJ-1 in response to isoflurane might act as a compensatory response for cell survival.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

References

  • Bandyopadhyay S, Cookson MR (2004) Evolutionary and functional relationships within the DJ1 superfamily. BMC Evol Biol 4:6

    Article  PubMed Central  PubMed  Google Scholar 

  • Baulac S, Lu H, Strahle J et al (2009) Increased DJ-1 expression under oxidative stress and in Alzheimer’s disease brains. Mol Neurodegener 4:12

    Article  PubMed Central  PubMed  Google Scholar 

  • Blackinton J, Lakshminarasimhan M, Thomas KJ et al (2009) Formation of a stabilized cysteine sulfinic acid is critical for the mitochondrial function of the parkinsonism protein DJ-1. J Biol Chem 284:6476–6485

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Cookson MR (2010) DJ-1, PINK1, and their effects on mitochondrial pathways. Mov Disord 25:S44–S48

    Article  PubMed Central  PubMed  Google Scholar 

  • Fulda S, Galluzzi L, Kroemer G (2010) Targeting mitochondria for cancer therapy. Nat Rev Drug Discov 9:447–464

    Article  CAS  PubMed  Google Scholar 

  • Johnsen D, Murphy SJ (2011) Isoflurane preconditioning protects astrocytes from oxygen and glucose deprivation independent of innate cell sex. J Neurosurg Anesthesiol 23(4):335–340

    Article  PubMed Central  PubMed  Google Scholar 

  • Junn E, Jang WH, Zhao X et al (2009) Mitochondrial localization of DJ-1 leads to enhanced neuroprotection. J Neurosci Res 87:123–129

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Kim RH, Smith PD, Aleyasin H et al (2005) Hypersensitivity of DJ-1-deficient mice to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyrindine (MPTP) and oxidative stress. Proc Natl Acad Sci U S A 102:5215–5220

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Kong F, Chen S, Cheng Y et al (2013) Minocycline attenuates cognitive impairment induced by isoflurane anesthesia in aged rats. PLoS One 8:e61385

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Kroemer G, Galluzzi L, Brenner C (2007) Mitochondrial membrane permeabilization in cell death. Physiol Rev 87:99–163

    Article  CAS  PubMed  Google Scholar 

  • Martinat C, Shendelman S, Jonason A et al (2004) Sensitivity to oxidative stress in DJ-1-deficient dopamine neurons: an ES- derived cell model of primary parkinsonism. PLoS Biol 2(11):e327

    Article  PubMed Central  PubMed  Google Scholar 

  • Mitchell P, Moyle J (1965) Stoichiometry of proton translocation through the respiratory chain and adenosine triphosphatase systems of rat liver mitochondria. Nature 208:147–151

    Article  CAS  PubMed  Google Scholar 

  • Moore DJ, West AB, Dawson VL, Dawson TM (2005) Molecular pathophysiology of Parkinson’s disease. Annu Rev Neurosci 28:57–87

    Article  CAS  PubMed  Google Scholar 

  • Nagakubo D, Taira T, Kitaura H et al (1997) DJ-1, a novel oncogene which transforms mouse NIH3T3 cells in cooperation with ras. Biochem Biophys Res Commun 231:509–513

    Article  CAS  PubMed  Google Scholar 

  • Rammes G, Starker LK, Haseneder R et al (2009) Isoflurane anaesthesia reversibly improves cognitive function and long-term potentiation (LTP) via an upregulation in NMDA receptor 2B subunit expression. Neuropharmacology 56:626–636

    Article  CAS  PubMed  Google Scholar 

  • Ren H, Fu K, Wang D et al (2011) Oxidized DJ-1 interacts with the mitochondrial protein BCL-XL. J Biol Chem 286:35308–35317

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Saelens X, Festjens N, Vande Walle L et al (2004) Vandenabeele toxic proteins released from mitochondria in cell death. Oncogene 23:2861–2874

    Article  CAS  PubMed  Google Scholar 

  • Sall JW, Stratmann G, Leong J et al (2009) Isoflurane inhibits growth but does not cause cell death in hippocampal neural precursor cells grown in culture. Anesthesiology 110(4):826–33

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Shen X, Bhatt N, Xu J, Meng T et al (2014) Effect of isoflurane on myocardial energetic and oxidative stress in cardiac muscle from Zucker diabetic fatty rat. J Pharmacol Exp Ther 349(1):21–28

    Article  PubMed Central  PubMed  Google Scholar 

  • Sheng B, Gong K, Niu Y et al (2009) Inhibition of gamma-secretase activity reduces Abeta production, reduces oxidative stress, increases mitochondrial activity and leads to reduced vulnerability to apoptosis: Implications for the treatment of Alzheimer’s disease. Free Radic Biol Med 46:1362–1375

    Article  CAS  PubMed  Google Scholar 

  • Taira T, Saito Y, Niki T et al (2004) DJ-1 has a role in antioxidative stress to prevent cell death. EMBO Rep 5:213–218

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Zhang Y, Dong Y, Wu X et al (2010) The mitochondrial pathway of anesthetic isoflurane-induced apoptosis. J Biol Chem 285(6):4025–37

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Zhang Y, Xu Z, Wang H et al (2012) Anesthetics isoflurane and desflurane differently affect mitochondrial function, learning, and memory. Ann Neurol 71(5):687–98

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Zhou F, Zhang L, Gong K et al (2008) LEF-1 activates the transcription of E2F1. Biochem Biophys Res Commun 365:149–153

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Qulian Guo.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Liu, W., Guo, Q., Hu, X. et al. Induction of DJ-1 protects neuronal cells from isoflurane induced neurotoxicity. Metab Brain Dis 30, 703–709 (2015). https://doi.org/10.1007/s11011-014-9622-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11011-014-9622-4

Keywords

Navigation