Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
권호 표지
DOI QR코드

DOI QR Code

Sinapic Acid Ameliorates REV-ERB α Modulated Mitochondrial Fission against MPTP-Induced Parkinson's Disease Model

  • Lee, Sang-Bin (Department of Integrative Biological Sciences and Industry, Sejong University) ;
  • Yang, Hyun Ok (Department of Integrative Biological Sciences and Industry, Sejong University)
  • Received : 2022.02.07
  • Accepted : 2022.04.26
  • Published : 2022.09.01
Download PDF
⟨ Previous Next ⟩

Abstract

Parkinson's disease (PD) is the second most common neurodegenerative disease worldwide, and accumulating evidence indicates that mitochondrial dysfunction is associated with progressive deterioration in PD patients. Previous studies have shown that sinapic acid has a neuroprotective effect, but its mechanisms of action remain unclear. The neuroprotective effect of sinapic acid was assayed in a PD mouse model generated by the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) as well as in SH-SY5Y cells. Target protein expression was detected by western blotting. Sinapic acid treatment attenuated the behavioral defects and loss of dopaminergic neurons in the PD models. Sinapic acid also improved mitochondrial function in the PD models. MPTP treatment increased the abundance of mitochondrial fission proteins such as dynamin-related protein 1 (Drp1) and phospho-Drp1 Ser616. In addition, MPTP decreased the expression of the REV-ERB α protein. These changes were attenuated by sinapic acid treatment. We used the pharmacological REV-ERB α inhibitor SR8278 to confirmation of protective effect of sinapic acid. Treatment of SR8278 with sinapic acid reversed the protein expression of phospho-Drp1 Ser616 and REV-ERB α on MPTP-treated mice. Our findings demonstrated that sinapic acid protects against MPTP-induced PD and these effects might be related to the inhibiting abnormal mitochondrial fission through REV-ERB α.

Keywords

Acknowledgement

This research was supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HI18C1860). This research was also supported by research funds from the National Research Foundation of Korea (NRF-2012M3A9C4048793) through the NRF funded by the Ministry of Education, Science, and Technology, Republic of Korea.

References

  1. Andrabi, S. S., Tabassum, H., Parveen, S. and Parvez, S. (2020) Ropinirole induces neuroprotection following reperfusion-promoted mitochondrial dysfunction after focal cerebral ischemia in Wistar rats. Neurotoxicology 77, 94-104. https://doi.org/10.1016/j.neuro.2019.12.004
  2. Belaid, H., Adrien, J., Karachi, C., Hirsch, E. C. and Francois, C. (2015) Effect of melatonin on sleep disorders in a monkey model of Parkinson's disease. Sleep Med. 16, 1245-1251. https://doi.org/10.1016/j.sleep.2015.06.018
  3. Bido, S., Soria, F. N., Fan, R. Z., Bezard, E. and Tieu, K. (2017) Mitochondrial division inhibitor-1 is neuroprotective in the A53T-alpha-synuclein rat model of Parkinson's disease. Sci. Rep. 7, 7495.
  4. Biorklund, G., Dadar, M., Anderson, G., Chirumbolo, S. and Maes, M. (2020) Preventive treatments to slow substantia nigra damage and Parkinson's disease progression: a critical perspective review. Pharmacol. Res. 161, 105065.
  5. Carter, S. J., Durrington, H. J., Gibbs, J. E., Blaikley, J., Loudon, A. S., Ray, D. W. and Sabroe, I. (2016) A matter of time: study of circadian clocks and their role in inflammation. J. Leukoc. Biol. 99, 549-560. https://doi.org/10.1189/jlb.3RU1015-451R
  6. Cho, B., Choi, S. Y., Cho, H. M., Kim, H. J. and Sun, W. (2013) Physiological and pathological significance of dynamin-related protein 1 (drp1)-dependent mitochondrial fission in the nervous system. Exp. Neurobiol. 22, 149-157. https://doi.org/10.5607/en.2013.22.3.149
  7. Ercolani, L., Ferrari, A., Mei, C. D., Parodi, C., Wade, M. and Grimaldi, B. (2015) Circadian clock: time for novel anticancer strategies? Pharmacol. Res. 100, 288-295. https://doi.org/10.1016/j.phrs.2015.08.008
  8. Goede, P., Wefers, J., Brombacher, E. C., Schrauwen, P. and Kalsbeek, A. (2018) Circadian rhythms in mitochondrial respiration. J. Mol. Endocrinol. 60, R115-R130. https://doi.org/10.1530/JME-17-0196
  9. Gong, C., Li, C., Qi, X., Song, Z., Wu, J., Hughes, M. E. and Li, X. (2015) The daily rhythms of mitochondrial gene expression and oxidative stress regulation are altered by ageing in the mouse liver. Chronobiol. Int. 32, 1254-1263. https://doi.org/10.3109/07420528.2015.1085388
  10. Hayashi, A., Matsunaga, N., Okazaki, H., Kakimoto, K., Kimura, Y., Azuma, Hiroki., Ikeda, E., Shiba, T., Yamato, M., Yamada, K., Koyanagi, S. and Ohdo, S. (2013) A disruption mechanism of the molecular clock in a MPTP mouse model of Parkinson's disease. Neuromolecular Med. 15, 238-251. https://doi.org/10.1007/s12017-012-8214-x
  11. Holownia, A., Chwiecko, M. and Farbiszewski, R. (1994) Accumulation of ammonia and changes in the activity of some ammonia metabolizing enzymes during brain ischaemia/reperfusion injury in rats. Mater. Med. Pol. 26, 25-27.
  12. Hu, Z., Mao, C., Wang, H., Zhang, Z., Zhang, S., Luo, H., Tang, M., Yang, J., Yuan, Y., Wang, Y., Liu, Y., Fan, L., Zhang, Q., Yao, D., Liu, F., Schisler, J. C., Shi, C. and Xu, Y. (2021) CHIP protects against MPP+/MPTP-induced damage by regulating Drp1 in two models of Parkinson's disease. Aging (Albany N.Y.) 13, 1458-1472.
  13. Kohsaka, A., Das, P., Hashimoto, I., Nakao, T., Deguchi, Y., Gouraud, S. S., Waki, H., Muragaki, Y. and Maeda, M. (2014) The circadian clock maintains cardiac function by regulating mitochondrial metabolism in mice. PLoS ONE 9, e112811.
  14. Kim, D. H., Yoon, B. H., Jung, W. Y., Kim, J. M., Park, S. J., Park, D. H., Huh, Y., Park, C., Cheong, J. H., Lee, K., Shin, C. Y. and Ryu, J. H. (2010) Sinapic acid attenuates kainic acid-induced hippocampal neuronal damage in mice. Neuropharmacology 59, 20-30. https://doi.org/10.1016/j.neuropharm.2010.03.012
  15. Kim, J., Jang, S., Choi, M., Chung, S., Choe, Y., Choe, H. K., Son, G. H., Rhee, K. and Kim, K. (2018) Abrogation of the circadian nuclear receptor REV-ERBalpha exacerbates 6-hydroxydopamine-induced dopaminergic neurodegeneration. Mol. Cells 41, 742-752.
  16. Laloux, C., Derambure, P., Houdayer, E., Jacquesson, J., Bordet, R., Destee, A. and Monaca, C. (2008) Effect of dopaminergic substances on sleep/wakefulness in saline- and MPTP-treated mice. J. Sleep Res. 17, 101-110. https://doi.org/10.1111/j.1365-2869.2008.00625.x
  17. Lauretti, E., Meco, A. D., Merali, S. and Pratico, D. (2017) Circadian rhythm dysfunction: a novel environmental risk factor for Parkinson's disease. Mol. Psychiatry 22, 280-286. https://doi.org/10.1038/mp.2016.47
  18. Lee, H. E., Kim, D. H., Park, S. J., Kim, J. M., Lee, Y. W., Jung, J. M., Lee, C. H., Hong, J. G., Liu, X., Cai, M., Park, K. J., Jang, D. S. and Ryu, J. H. (2012) Neuroprotective effect of sinapic acid in a mouse model of amyloid beta(1-42) protein-induced Alzheimer's disease. Pharmacol. Biochem. Behav. 103, 260-266. https://doi.org/10.1016/j.pbb.2012.08.015
  19. Lee, S., Youn, J., Jang, W. and Yang, H. O. (2019) Neuroprotective effect of anodal transcranial direct current stimulation on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity in mice through modulating mitochondrial dynamics. Neurochem. Int. 129, 104491.
  20. Li, H., Feng, Y., Chen, Z., Jiang, X., Zhou, Z., Yuan, J., Li, F., Zhang, Y., Huang, X., Fan, S., Wu, X. and Huang, C. (2021a) Pepper component 7-ethoxy-4-methylcoumarin, a novel dopamine D2 receptor agonist, ameliorates experimental Parkinson's disease in mice and Caenorhabditis elegans. Pharmacol. Res. 163, 105220.
  21. Li, H., Kim, J., Tran, H. N. K., Lee, C. H., Hur, J., Kim, M. C. and Yang, H. O. (2021b) Extract of Polygala tenuifolia, Angelica tenuissima, and Dimocarpus longan reduces behavioral defect and enhances autophagy in experimental models of Parkinson's disease. Neuromolecular Med. 23, 428-443. https://doi.org/10.1007/s12017-020-08643-x
  22. Li, X., Lin, J., Ding, X., Xuan, J., Hu, Z., Wu, D., Zhu, X., Feng, Z., Ni, W. and Wu, A. (2019) The protective effect of sinapic acid in osteoarthritis: in vitro and in vivo studies. J. Cell. Mol. Med. 23, 1940-1950. https://doi.org/10.1111/jcmm.14096
  23. Mishra, A., Singh, S., Tiwari, V., Bano, S. and Shukla, S. (2020) Dopamine D1 receptor agonism induces dynamin related protein-1 inhibition to improve mitochondrial biogenesis and dopaminergic neurogenesis in rat model of Parkinson's disease. Behav. Brain Res. 378, 112304.
  24. Park, J., Seo, J., Won, J., Yeo, H., Ahn, Y., Kim, K., Jin, Y., Koo, B., Lim, K. S., Jeong, K., Kang, P., Lee, H., Baek, S. H., Jeon, C., Hong, J., Huh, J., Kim, Y., Park, S., Kim, S., Lee, D., Lee, S. and Lee, Y. (2019) Abnormal mitochondria in a non-human primate model of MPTP-induced Parkinson's disease: Drp1 and CDK5/p25 signaling. Exp. Neurobiol. 28, 414-424. https://doi.org/10.5607/en.2019.28.3.414
  25. Qi, X., Qvit, N., Su, Y. C. and Mochly-Rosen, D. A. (2013) A novel Drp1 inhibitor diminishes aberrant mitochondrial fission and neurotoxicity. J. Cell Sci. 126, 789-802.
  26. Roby, D. A., Ruiz, F., Kermath, B. A., Voorhees, J. R., Niehoff, M., Zhang, J., Morley, J. E., Musiek, E. S., Farr, S. A. and Burris, T. P. (2019) Pharmacological activation of the nuclear receptor REV-ERB reverses cognitive deficits and reduces amyloid-β burden in a mouse model of Alzheimer's disease. PLoS ONE 14, e0215004.
  27. Roe, A. J. and Qi, X. (2018) Drp1 phosphorylation by MAPK1 causes mitochondrial dysfunction in cell culture model of Huntington's disease. Biochem. Biophys. Res. Commun. 496, 706-711. https://doi.org/10.1016/j.bbrc.2018.01.114
  28. Rudenok, M. M., Alieva, A. K., Starovatykh, J. S., Nesterov, M. S., Stanishevskaya, V. A., Kolacheva, A. A., Ugryumov, M. V., Slominsky, P. A. and Shadrina, M. I. (2020) Expression analysis of genes involved in mitochondrial biogenesis in mice with MPTP-induced model of Parkinson's disease. Mol. Genet. Metab. Rep. 23, 100584.
  29. Shahmohamady, P., Eidi, A., Mortazavi, P., Panahi, N. and Minai-Tehrani, D. (2018) Effect of sinapic acid on memory deficits and neuronal degeneration induced by intracerebroventricular administration of streptozotocin in rats. Pol. J. Pathol. 69, 266-277. https://doi.org/10.5114/pjp.2018.79546
  30. Shirihai, O. S., Song, M. and Dorn, G. W., 2nd (2015) How mitochondrial dynamism orchestrates mitophagy. Circ. Res. 116, 1835-1849. https://doi.org/10.1161/CIRCRESAHA.116.306374
  31. Stujanna, E. N., Murakoshi, N., Tajiri, K., Xu, D., Kimura, T., Qin, R., Feng, D., Yonebayashi, S., Ogura, Y., Yamagami, F., Sato, A., Nogami, A. and Aonuma, K. (2017) Rev-erb agonist improves adverse cardiac remodeling and survival in myocardial infarction through an anti-inflammatory mechanism. PLoS ONE 12, e0189330.
  32. Suen, D. F., Norris, K. L. and Youle, R. J. (2008) Mitochondrial dynamics and apoptosis. Genes Dev. 22, 1577-1590. https://doi.org/10.1101/gad.1658508
  33. Videnovic, A. and Golombek, D. (2013) Circadian and sleep disorders in Parkinson's disease. Exp. Neurol. 243, 45-56. https://doi.org/10.1016/j.expneurol.2012.08.018
  34. Wang, Y., Lv, D., Liu, W., Li, S., Chen, J., Shen, Y., Wang, F., Hu, L. and Liu, C. (2018) Disruption of the circadian clock alters antioxidative defence via the SIRT1-BMAL1 pathway in 6-OHDA-induced models of Parkinson's disease. Oxid. Med. Cell. Longev. 2018, 4854732.
  35. Welch, R. D., Billon, C., Valfort, A. C., Burris, T. P. and Flaveny, C. A. (2017) Pharmacological inhibition of REV-ERB stimulates differentiation, inhibits turnover and reduces fibrosis in dystrophic muscle. Sci. Rep. 7, 17142.
  36. Woldt, E., Sebti, Y., Solt, L. A., Duhem, C., Lancel, S., Eeckhoutem J., Hesselink, M. K. C., Paquet, C., Delhaye, S., Shin, Y., Kamenecka, T. M., Schaart, G., Lefebvre, P., Neviere, R., Burris, T. P., Schrauwen, P., Staels, B. and Duez, H. (2013) Rev-erb-alpha modulates skeletal muscle oxidative capacity by regulating mitochondrial biogenesis and autophagy. Nat. Med. 19, 1039-1046. https://doi.org/10.1038/nm.3213
  37. Xie, Y., Tang, Q., Chen, G., Xie, M., Yu, S., Zhao, J. and Chen, L. (2019) New insights into the circadian rhythm and its related diseases. Front. Physiol. 10, 682.
  38. Yang, C., Deng, Q., Xu, J., Wang, X., Hu, C., Tang, H. and Huang, F. (2019) Sinapic acid and resveratrol alleviate oxidative stress with modulation of gut microbiota in high-fat diet-fed rats Food Res. Int. 116, 1202-1211. https://doi.org/10.1016/j.foodres.2018.10.003
  39. Yoon, B. H., Jung, J. W., Lee, J., Cho, Y., Jang, C., Jin, C., Oh, T. H. and Ryu, J. H. (2007) Anxiolytic-like effects of sinapic acid in mice. Life Sci. 81, 234-240. https://doi.org/10.1016/j.lfs.2007.05.007
  40. Zare, K., Eidi, A., Roghani, M. and Rohani, A. H. (2015) The neuroprotective potential of sinapic acid in the 6-hydroxydopamine-induced hemi-parkinsonian rat. Metab. Brain Dis. 30, 205-213. https://doi.org/10.1007/s11011-014-9604-6
  41. Zhao, F., Austria, Q., Wang, W. and Zhu, X. (2021) Mfn2 overexpression attenuates MPTP neurotoxicity in vivo. Int. J. Mol. Sci. 22, 601.
  42. Zheng, J. L., Yuan, S. S., Wu, C. W., Lv, Z. M. and Zhu, A. Y. (2017) Circadian time-dependent antioxidant and inflammatory responses to acute cadmium exposure in the brain of zebrafish. Aquat. Toxicol. 182, 113-119. https://doi.org/10.1016/j.aquatox.2016.11.017
  43. Zhou, J., Zhao, Y., Li, Z., Zhu, M., Wang, Z., Li, Y., Xu, T., Feng, D., Zhang, S., Tang, F. and Yao, J. (2020) miR-103a-3p regulates mitophagy in Parkinson's disease through Parkin/Ambra1 signaling. Pharmacol. Res. 160, 105197.