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β-Asarone Inhibits IRE1/XBP1 Endoplasmic Reticulum Stress Pathway in 6-OHDA-Induced Parkinsonian Rats

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Abstract

Parkinson’s disease (PD) is a neurodegenerative disease, with genetics and environment contributing to the disease onset. The limited pathological cognize of the disease restrained the approaches to improve the clinical treatment. Recently, studies showed that endoplasmic reticulum (ER) stress played an important role in the pathogenesis of PD. There was a neuroprotective effect partly mediated by modulating ER stress. β-Asarone is the essential constituent of Acorus tatarinowii Schott volatile oil. Our team observed that β-asarone could improve the behavior of parkinsonian rats; increase the HVA, Dopacl, and 5-HIAA levels; and reduce α-synuclein levels. Here we assumed that the protective role of β-asarone on parkinsonian rats was mediated via ER stress pathway. To prove the hypothesis we investigated the mRNA levels of glucose regulated protein 78 (GRP78) and C/EBP homologous binding protein (CHOP) in 6-hydroxy dopamine (6-OHDA) induced parkinsonian rats after β-asarone treatment. Furthermore, the inositol-requiring enzyme 1/X-Box Binding Protein 1 (IRE1/XBP1) ER stress pathway was also studied. The results showed that β-asarone inhibited the mRNA levels of GRP78 and CHOP, accompanied with the delined expressions of phosphorylated IER1 (p-IRE1) and XBP1. We deduced that β-asarone might have a protective effect on the 6-OHDA induced parkinsonian rats via IRE1/XBP1 Pathway. Collectively, all data indicated that β-asarone might be a potential candidate of medicine for clinical therapy of PD.

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References

  1. Mhyre TR, Boyd JT, Hamill RW et al (2012) Parkinson’s disease. Subcell Biochem 65:389–455

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Fahn S, Sulzer D (2004) Neurodegeneration and neuroprotection in Parkinson disease. Neuro Rx 1:139–154

    Article  Google Scholar 

  3. Wakabayashi K, Tanji K, Mori F et al (2007) The Lewy body in Parkinson’s disease: molecules implicated in the formation and degradation of alpha-synuclein aggregates. Neuropathology 27:494–506

    Article  PubMed  Google Scholar 

  4. Stefanis L (2012) α-Synuclein in Parkinson’s disease. Cold Spring Harb Perspect Med 2:a009399

    Article  PubMed  PubMed Central  Google Scholar 

  5. Dias V, Junn E, Mouradian MM (2013) The role of oxidative stress in Parkinson’s disease. J Parkinsons Dis 3:461–491

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Jenner P (2003) Oxidative stress in Parkinson’s disease. Ann Neurol 53:S26–S36

    Article  CAS  PubMed  Google Scholar 

  7. Schröder ER, Kaufman RJ (2005) ER stress and the unfolded protein response. Mutat Res 569:29–63

    Article  PubMed  Google Scholar 

  8. Ryu EJ, Harding HP, Angelastro JM et al (2002) Endoplasmic reticulum stress and the unfolded protein response in cellular models of Parkinson’s disease. J Neurosci 22:10690–10698

    CAS  PubMed  Google Scholar 

  9. Hoozemans JJ, van Haastert ES, Eikelenboom P et al (2007) Activation of the unfolded protein response in Parkinson’s disease. Biochem Biophys Res Commun 354:707–711

    Article  CAS  PubMed  Google Scholar 

  10. Jiang P, Gan M, Ebrahim AS et al (2010) ER stress response plays an important role in aggregation of α-synuclein. Mol Neurodegener 5:56

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Holtz WA, Turetzky JM, Jong YJ et al (2006) Oxidative stress-triggered unfolded protein response is upstream of intrinsic cell death evoked by parkinsonian mimetics. J Neurochem 99:54–69

    Article  CAS  PubMed  Google Scholar 

  12. Sado M, Yamasaki Y, Iwanaga T et al (2009) Protective effect against Parkinson’s disease-related insults through the activation of XBP1. Brain Res 1257:16–24

    Article  CAS  PubMed  Google Scholar 

  13. Janyou A, Changtam C, Suksamrarn A et al (2015) Suppression effects of O-demethyldemethoxycurcumin on thapsigargin triggered on endoplasmic reticulum stress in SK-N-SH cells. Neurotoxicology 50:92–100

    Article  CAS  PubMed  Google Scholar 

  14. Fang YQ, Shi C, Liu L et al (2012) Pharmacokinetics of beta-asarone in rabbit blood, hippocampus, cortex, brain stem, thalamus and cerebellum. Pharmazie 67:120–123

    CAS  PubMed  Google Scholar 

  15. Zhang S, Gui XH, Huang LP et al (2016) Neuroprotective effects of β-asarone against 6-hydroxy dopamine-induced parkinsonism via JNK/Bcl-2/Beclin-1 pathway. Mol Neurobiol 53:83–94

    Article  CAS  PubMed  Google Scholar 

  16. Huang LP, Deng MZ, He YP et al (2015) β-Asarone and levodopa co-administration protects against 6-hydroxydopamine-induced damage in parkinsonian rat mesencephalon by regulating autophagy: down-expression Beclin-1 and light chain 3B and up-expression P62. Clin Exp Pharmacol Physiol 42:269–277

    Article  CAS  PubMed  Google Scholar 

  17. Liu L, Fang YQ (2011) Analysis of the distribution of beta-asarone in rat hippocampus, brainstem, cortex and cerebellum with gas chromatography-mass spectrometry (GC-MS). J Med Plants Res 5:1728–1734

    CAS  Google Scholar 

  18. Paxinos G, Watson C (1982) The rat brain in stereotaxic coordinates. Academic Press, San Diego

    Google Scholar 

  19. Saracchi E, Fermi S, Brighina L (2014) Emerging candidate biomarkers for Parkinson’s disease: a review. Aging Dis 5:27–34

    Article  PubMed  Google Scholar 

  20. Jankovic J (2008) Parkinson’s disease: clinical features and diagnosis. J Neurol Neurosurg Psychiatry 79:368–376

    Article  CAS  PubMed  Google Scholar 

  21. Fahn S (2000) The spectrum of levodopa-induced dyskinesias. Ann Neurol 47:2–11

    Article  Google Scholar 

  22. Ungerstedt U (1968) 6-Hydroxydopamine induced degeneration of central monoamine neurons. Eur J Pharmacol 5:107–110

    Article  CAS  PubMed  Google Scholar 

  23. Dauer W, Przedborski S (2003) Parkinson’s disease: mechanisms and models. Neuron 39:889–909

    Article  CAS  PubMed  Google Scholar 

  24. Kearns CM, Cass WA, Smoot K et al (1997) GDNF protection against 6-OHDA: time dependence and requirement for protein synthesis. J Neurosci 17:7111–7118

    CAS  PubMed  Google Scholar 

  25. Shults CW, Ray Jasodhara R, Tsuboi K et al (2000) Fibroblast growth factor-2-producing fibroblasts protect the nigrostriatal dopaminergic system from 6-hydroxydopamine. Brain Res 883:192–204

    Article  CAS  PubMed  Google Scholar 

  26. Peterson AL, Nutt JG (2008) Treatment of Parkinson’s disease with trophic factors. Neurotherapeutics 5:270–280

    Article  CAS  PubMed  Google Scholar 

  27. Cho J, Ho KY, Kong JY (1998) Protection of cultured rat cortical neurons from excitotoxicity by asarone, a major essential oil component in the rhizomes of Acorus gramineus. Life Sci 5:591–599

    Google Scholar 

  28. Fang YQ, Li L, Wu QD (2003) Effects of beta-asarone on gene expression in mouse brain. Zhong Yao Cai 9:650–652

    Google Scholar 

  29. Imai Y, Soda M, Inoue H et al (2001) An unfolded putative transmembrane polypeptide, which can lead to endoplasmic reticulum stress, is a substrate of Parkin. Cell 105:891–902

    Article  CAS  PubMed  Google Scholar 

  30. Holtz WA, O’Malley KL (2003) Parkinsonian mimetics induce aspects of unfolded protein response in death of dopaminergic neurons. J Biol Chem 278:19367–19377

    Article  CAS  PubMed  Google Scholar 

  31. Bernales S, Soto MM, McCullagh E (2012) Unfolded protein stress in the endoplasmic reticulum and mitochondria: a role in neurodegeneration. Front Aging Neurosci 4:5

    Article  PubMed  PubMed Central  Google Scholar 

  32. Lee AS (2005) The ER chaperone and signaling regulator GRP78/BiP as a monitor of endoplasmic reticulum stress. Methods 35:373–381

    Article  CAS  PubMed  Google Scholar 

  33. Selvaraj S, Sun Y, Watt JA et al (2012) Neurotoxin-induced ER stress in mouse dopaminergic neurons involves downregulation of TRPC1 and inhibition of AKT/mTOR signaling. J Clin Invest 122:1354–1367

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Jin ML, Park SY, Kim YH et al (2014) The neuroprotective effects of cordycepin inhibit glutamate-induced oxidative and ER stress-associated apoptosis in hippocampal HT22 cells. Neurotoxicology 41:102–111

    Article  CAS  PubMed  Google Scholar 

  35. Schroder M, Kaufman RJ (2005) The mammalian unfolded protein response. Annu Rev Biochem 74:739–789

    Article  PubMed  Google Scholar 

  36. Gardner BM, Pincus D, Gotthardt K et al (2013) Endoplasmic reticulum stress sensing in the unfolded protein response. Cold Spring Harb Perspect Biol 5:a013169

    Article  PubMed  PubMed Central  Google Scholar 

  37. Yang W, Tiffany-Castiglioni E, Koh HC et al (2009) Paraquat activates the IRE1/ASK1/JNK cascade associated with apoptosis in human neuroblastoma SH-SY5Y cells. Toxicol Lett 191:203–210

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This work was supported by the Guangdong Natural Science Foundation of China (Grant no. S2012010010625).

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Correspondence to Yongqi Fang.

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The authors declare that there are no conflicts of interest.

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Baile Ning, Minzhen Deng and Qinxin Zhang contributed equally to the work and should be considered as co-first authors.

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Ning, B., Deng, M., Zhang, Q. et al. β-Asarone Inhibits IRE1/XBP1 Endoplasmic Reticulum Stress Pathway in 6-OHDA-Induced Parkinsonian Rats. Neurochem Res 41, 2097–2101 (2016). https://doi.org/10.1007/s11064-016-1922-0

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