SH-SY5Y cells undergo changes in peroxisomal metabolism when exposed to decanoic acid.
C10
C8
MCT diet
metabolism
peroxisome
seizures
Journal
Journal of neurochemistry
ISSN: 1471-4159
Titre abrégé: J Neurochem
Pays: England
ID NLM: 2985190R
Informations de publication
Date de publication:
17 Jul 2024
17 Jul 2024
Historique:
revised:
03
07
2024
received:
02
05
2024
accepted:
08
07
2024
medline:
17
7
2024
pubmed:
17
7
2024
entrez:
17
7
2024
Statut:
aheadofprint
Résumé
Medium-chain fatty acids (MCFAs), particularly decanoic acid (C10) and octanoic acid (C8), have garnered attention in recent years for their potential antiepileptic properties. A previous study from our laboratory demonstrated that C10 targets the PPARγ nuclear receptor, increasing the activity of the antioxidant enzyme catalase and thereby possibly modulating peroxisomal content. Here, we examined markers of peroxisomal content and activity in response to C10 and C8 exposure in neuronal-like SH-SY5Y cells. SH-SY5Y were treated with 250 mM C10 or C8 for a period of 6 days. Following this, biochemical markers of peroxisomal content and function were assessed, including acyl-coA oxidase activity, peroxisomal gene expression and peroxisomal VLCFA β-oxidation. Our findings revealed that C10 treatment augments acyl-CoA oxidase 1 (ACOx1) activity by 129% in comparison to control cells. An exploration into genes related to peroxisomal biosynthesis showed 23% increased expression of PEX11α upon C10 exposure, implying peroxisomal proliferation. Furthermore, it was observed that C10 exposure not only elevated ACOx1 activity but also enhanced peroxisomal β-oxidation of docosanoic acid (C22). Our findings bolster the premise that C10 functions as a peroxisome proliferator, influencing peroxisomal content and function. Further investigations are required to fully understand the mechanistic details as to how this may be beneficial in epilepsy and the potential implications with regards to peroxisomal disease.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2024 The Author(s). Journal of Neurochemistry published by John Wiley & Sons Ltd on behalf of International Society for Neurochemistry.
Références
Bradford, M. M. (1976). A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein‐dye binding. Analytical Biochemistry, 72(1–2), 248–254. https://doi.org/10.1016/0003‐2697(76)90527‐3
Chang, P., Augustin, K., Boddum, K., Williams, S., Sun, M., Terschak, J. A., Hardege, J. D., Chen, P. E., Walker, M. C., & Williams, R. S. B. (2016). Seizure control by decanoic acid through direct AMPA receptor inhibition. Brain, 139(2), 431–443. https://doi.org/10.1093/brain/awv325
Chen, X.‐F., Tian, M.‐X., Sun, R.‐Q., Zhang, M.‐L., Zhou, L.‐S., Jin, L., Chen, L.‐L., Zhou, W.‐J., Duan, K.‐L., Chen, Y.‐J., Gao, C., Cheng, Z.‐L., Wang, F., Zhang, J.‐Y., Sun, Y.‐P., Yu, H.‐X., Zhao, Y.‐Z., Yang, Y., Liu, W.‐R., … Ye, D. (2018). SIRT5 inhibits peroxisomal ACOX1 to prevent oxidative damage and is downregulated in liver cancer. EMBO Reports, 19(5), e45124. https://doi.org/10.15252/embr.201745124
Demarquoy, J. (2015). Crosstalk between mitochondria and peroxisomes. World Journal of Biological Chemistry, 6(4), 301–309. https://doi.org/10.4331/wjbc.v6.i4.301
Diano, S., Liu, Z.‐W., Jeong, J. K., Dietrich, M. O., Ruan, H.‐B., Kim, E., Suyama, S., Kelly, K., Gyengesi, E., Arbiser, J. L., Belsham, D. D., Sarruf, D. A., Schwartz, M. W., Bennett, A. M., Shanabrough, M., Mobbs, C. V., Yang, X., Gao, X.‐B., & Horvath, T. L. (2011). Peroxisome proliferation–associated control of reactive oxygen species sets melanocortin tone and feeding in diet‐induced obesity. Nature Medicine, 17(9), 1121–1127. https://doi.org/10.1038/nm.2421
Hughes, S. D., Kanabus, M., Anderson, G., Hargreaves, I. P., Rutherford, T., O'Donnell, M., Cross, J. H., Rahman, S., Eaton, S., & Heales, S. J. R. (2014). The ketogenic diet component decanoic acid increases mitochondrial citrate synthase and complex I activity in neuronal cells. Journal of Neurochemistry, 129(3), 426–433. https://doi.org/10.1111/jnc.12646
Jancovski, N., Baldwin, T., Orford, M., Li, M., Jones, G. D., Burbano, L. E., Rutherford, T., Reid, C., Heales, S., Eaton, S., & Petrou, S. (2021). Protective effects of medium chain triglyceride diet in a mouse model of Dravet syndrome. Epilepsia, 62(12), 3131–3142. https://doi.org/10.1111/epi.17101
Janssen, A., Gressens, P., Grabenbauer, M., Baumgart, E., Schad, A., Vanhorebeek, I., Brouwers, A., Declercq, P. E., Fahimi, D., Evrard, P., Schoonjans, L., Collen, D., Carmeliet, P., Mannaerts, G., Van Veldhoven, P., & Baes, M. (2003). Neuronal migration depends on intact peroxisomal function in brain and in extraneuronal tissues. The Journal of Neuroscience: The Official Journal of the Society for Neuroscience, 23(30), 9732–9741. https://doi.org/10.1523/JNEUROSCI.23‐30‐09732.2003
Jo, D. S., Park, N. Y., & Cho, D.‐H. (2020). Peroxisome quality control and dysregulated lipid metabolism in neurodegenerative diseases. Experimental & Molecular Medicine, 52(9), 1486–1495. https://doi.org/10.1038/s12276‐020‐00503‐9
Júnior, H. V. N., de França Fonteles, M. M., & Mendes de Freitas, R. (2009). Acute seizure activity promotes lipid peroxidation, increased nitrite levels and adaptive pathways against oxidative stress in the frontal cortex and striatum. Oxidative Medicine and Cellular Longevity, 2(3), 130–137. https://doi.org/10.4161/oxim.2.3.8488
Kassmann, C. M. (2014). Myelin peroxisomes ‐ essential organelles for the maintenance of white matter in the nervous system. Biochimie, 98, 111–118. https://doi.org/10.1016/j.biochi.2013.09.020
Khabbush, A., Orford, M., Tsai, Y.‐C., Rutherford, T., O'Donnell, M., Eaton, S., & Heales, S. J. R. (2017). Neuronal decanoic acid oxidation is markedly lower than that of octanoic acid: A mechanistic insight into the medium‐chain triglyceride ketogenic diet. Epilepsia, 58(8), 1423–1429. https://doi.org/10.1111/epi.13833
Khalil, Y., Carrino, S., Lin, F., Ferlin, A., Lad, H. V., Mazzacuva, F., Falcone, S., Rivers, N., Banks, G., Concas, D., Aguilar, C., Haynes, A. R., Blease, A., Nicol, T., Al‐Shawi, R., Heywood, W., Potter, P., Mills, K., Gale, D. P., & Clayton, P. T. (2022). Tissue proteome of 2‐hydroxyacyl‐CoA lyase deficient mice reveals peroxisome proliferation and activation of ω‐oxidation. International Journal of Molecular Sciences, 23(2), 987. https://doi.org/10.3390/ijms23020987
Kheir, A. E. M. (2011). Zellweger syndrome: A cause of neonatal hypotonia and seizures. Sudanese Journal of Paediatrics, 11(2), 54–58.
Koepke, J. I., Nakrieko, K., Wood, C. S., Boucher, K. K., Terlecky, L. J., Walton, P. A., & Terlecky, S. R. (2007). Restoration of Peroxisomal catalase import in a model of human cellular aging. Traffic, 8(11), 1590–1600. https://doi.org/10.1111/j.1600‐0854.2007.00633.x
Kossoff, E. H., Zupec‐Kania, B. A., & Rho, J. M. (2009). Ketogenic diets: An update for child neurologists. Journal of Child Neurology, 24(8), 979–988. https://doi.org/10.1177/0883073809337162
Lee, M. J., Gee, P., & Beard, S. E. (1997). Detection of peroxisome proliferators using a reporter construct derived from the rat acyl‐CoA oxidase promoter in the rat liver cell line H‐4‐II‐E. Cancer Research, 57(8), 1575–1579.
Liepinsh, E., Skapare, E., Kuka, J., Makrecka, M., Cirule, H., Vavers, E., Sevostjanovs, E., Grinberga, S., Pugovics, O., & Dambrova, M. (2013). Activated peroxisomal fatty acid metabolism improves cardiac recovery in ischemia‐reperfusion. Naunyn‐Schmiedeberg's Archives of Pharmacology, 386(6), 541–550. https://doi.org/10.1007/s00210‐013‐0849‐0
Likhodii, S. S., Musa, K., Mendonca, A., Dell, C., Burnham, W. M., & Cunnane, S. C. (2000). Dietary fat, ketosis, and seizure resistance in rats on the ketogenic diet. Epilepsia, 41(11), 1400–1410. https://doi.org/10.1111/j.1528‐1157.2000.tb00115.x
Livak, K. J., & Schmittgen, T. D. (2001). Analysis of relative gene expression data using real‐time quantitative PCR and the 2−ΔΔCT method. Methods, 25(4), 402–408. https://doi.org/10.1006/meth.2001.1262
Malapaka, R. R. V., Khoo, S., Zhang, J., Choi, J. H., Zhou, X. E., Xu, Y., Gong, Y., Li, J., Yong, E.‐L., Chalmers, M. J., Chang, L., Resau, J. H., Griffin, P. R., Chen, Y. E., & Xu, H. E. (2012). Identification and mechanism of 10‐carbon fatty acid as modulating ligand of peroxisome proliferator‐activated receptors. Journal of Biological Chemistry, 287(1), 183–195. https://doi.org/10.1074/jbc.M111.294785
Monternier, P.‐A., Singh, J., Parasar, P., Theurey, P., DeWitt, S., Jacques, V., Klett, E., Kaur, N., Nagaraja, T. N., Moller, D. E., & Hallakou‐Bozec, S. (2022). Therapeutic potential of deuterium‐stabilized (R)‐pioglitazone‐PXL065‐for X‐linked adrenoleukodystrophy. Journal of Inherited Metabolic Disease, 45(4), 832–847. https://doi.org/10.1002/jimd.12510
Neal, E. (2012). The medium‐chain triglyceride ketogenic diet. In Dietary treatment of epilepsy: Practical implementation of ketogenic therapy (pp. 78–88). Wiley. https://doi.org/10.1002/9781118702772.ch9
Neal, E. G., Chaffe, H., Schwartz, R. H., Lawson, M. S., Edwards, N., Fitzsimmons, G., Whitney, A., & Cross, J. H. (2009). A randomized trial of classical and medium‐chain triglyceride ketogenic diets in the treatment of childhood epilepsy. Epilepsia, 50(5), 1109–1117. https://doi.org/10.1111/j.1528‐1167.2008.01870.x
Rho, J. M., Anderson, G. D., Donevan, S. D., & White, H. S. (2002). Acetoacetate, acetone, and Dibenzylamine (a contaminant in l −(+)‐β‐hydroxybutyrate) exhibit direct anticonvulsant actions in vivo. Epilepsia, 43(4), 358–361. https://doi.org/10.1046/j.1528‐1157.2002.47901.x
Sasabe, J., Suzuki, M., Imanishi, N., & Aiso, S. (2014). Activity of D‐amino acid oxidase is widespread in the human central nervous system. Frontiers in Synaptic Neuroscience, 6, 14. https://doi.org/10.3389/fnsyn.2014.00014
Sato, E., Kurokawa, T., Oda, N., & Ishibashi, S. (1996). Early appearance of abnormality of microperoxisomal enzymes in the cerebral cortex of senescence‐accelerated mouse. Mechanisms of Ageing and Development, 92(2–3), 175–184. https://doi.org/10.1016/S0047‐6374(96)01832‐5
Schoeler, N. E., Orford, M., Vivekananda, U., Simpson, Z., Van de Bor, B., Smith, H., Balestrini, S., Rutherford, T., Brennan, E., McKenna, J., Lambert, B., Barker, T., Jackson, R., Williams, R. S. B., Sisodiya, S. M., Eaton, S., Heales, S. J. R., Cross, J. H., Walker, M. C., … Rahman, S. (2021). K.Vita: A feasibility study of a blend of medium chain triglycerides to manage drug‐resistant epilepsy. Brain Communications, 3(4), fcab160. https://doi.org/10.1093/braincomms/fcab160
Schrader, M., Bonekamp, N. A., & Islinger, M. (2012). Fission and proliferation of peroxisomes. Biochimica et Biophysica Acta (BBA) ‐ Molecular Basis of Disease, 1822(9), 1343–1357. https://doi.org/10.1016/j.bbadis.2011.12.014
Shah, P., & Mudaliar, S. (2010). Pioglitazone: Side effect and safety profile. Expert Opinion on Drug Safety, 9(2), 347–354. https://doi.org/10.1517/14740331003623218
Small, G. M., Burdett, K., & Connock, M. J. (1985). A sensitive spectrophotometric assay for peroxisomal acyl‐CoA oxidase. Biochemical Journal, 227(1), 205–210. https://doi.org/10.1042/bj2270205
Tong, X., Deng, Y., Liu, L., Tang, X., Yu, T., Gan, J., Cai, Q., Luo, R., & Xiao, N. (2022). Clinical implementation of ketogenic diet in children with drug‐resistant epilepsy: Advantages, disadvantages, and difficulties. Seizure: European Journal of Epilepsy, 99, 75–81. https://doi.org/10.1016/j.seizure.2022.04.015
van de Beek, M.‐C., Dijkstra, I. M. E., & Kemp, S. (2017). Method for Measurement of Peroxisomal Very Long‐Chain Fatty Acid Beta‐Oxidation and De Novo C26:0 Synthesis Activity in Living Cells Using Stable‐Isotope Labeled Docosanoic Acid (pp. 45–54). https://doi.org/10.1007/978‐1‐4939‐6937‐1_5
Walton, P. A. (2012). Effects of peroxisomal catalase inhibition on mitochondrial function. Frontiers in Physiology, 3, article 108. https://doi.org/10.3389/fphys.2012.00108
Zanardelli, M., Micheli, L., Cinci, L., Failli, P., Ghelardini, C., & Di Cesare Mannelli, L. (2014). Oxaliplatin neurotoxicity involves peroxisome alterations. PPARγ Agonism as preventive pharmacological approach. PLoS One, 9(7), e102758. https://doi.org/10.1371/journal.pone.0102758