Experimental and Molecular Medicine

  • 제49권1호
  • /
  • Pages.6.1-6.11
  • /
  • 2017
  • /
  • 1226-3613(pISSN)
  • /
  • 2092-6413(eISSN)
생화학분자생물학회 (Korean Society for Biochemistry and Molecular Biongy)
권호 표지
DOI QR코드

DOI QR Code

Docosahexaenoic acid-mediated protein aggregates may reduce proteasome activity and delay myotube degradation during muscle atrophy in vitro

  • Shin, Seung Kyun (Department of Applied Chemistry, College of Applied Sciences, Kyung Hee University) ;
  • Kim, Ji Hyeon (Department of Biomedical Sciences, Seoul National University Graduate School) ;
  • Lee, Jung Hoon (Department of Biochemistry and Molecular Biology, Seoul National University College of Medicine) ;
  • Son, Young Hoon (Department of Biomedical Sciences, Seoul National University Graduate School) ;
  • Lee, Min Wook (Department of Chemistry, College of Science, Korea University) ;
  • Kim, Hak Joong (Department of Chemistry, College of Science, Korea University) ;
  • Noh, Sue Ah (Department of Applied Chemistry, College of Applied Sciences, Kyung Hee University) ;
  • Kim, Kwang Pyo (Department of Applied Chemistry, College of Applied Sciences, Kyung Hee University) ;
  • Kim, In-Gyu (Department of Biomedical Sciences, Seoul National University Graduate School) ;
  • Lee, Min Jae (Department of Biomedical Sciences, Seoul National University Graduate School)
  • 투고 : 2016.05.06
  • 심사 : 2016.09.19
  • 발행 : 2017.01.31
⟨ 이전 논문 다음 논문 ⟩

초록

Proteasomes are the primary degradation machinery for oxidatively damaged proteins that compose a class of misfolded protein substrates. Cellular levels of reactive oxygen species increase with age and this cellular propensity is particularly harmful when combined with the age-associated development of various human disorders including cancer, neurodegenerative disease and muscle atrophy. Proteasome activity is reportedly downregulated in these disease conditions. Herein, we report that docosahexaenoic acid (DHA), a major dietary omega-3 polyunsaturated fatty acid, mediates intermolecular protein cross-linkages through oxidation, and the resulting protein aggregates potently reduce proteasomal activity both in vitro and in cultured cells. Cellular models overexpressing aggregation-prone proteins such as tau showed significantly elevated levels of tau aggregates and total ubiquitin conjugates in the presence of DHA, thereby reflecting suppressed proteasome activity. Strong synergetic cytotoxicity was observed when the cells overexpressing tau were simultaneously treated with DHA. Antioxidant N-acetyl cysteine significantly desensitized the cells to DHA-induced oxidative stress. DHA significantly delayed the proteasomal degradation of muscle proteins in a cellular atrophy model. Thus, the results of our study identified DHA as a potent inducer of cellular protein aggregates that inhibit proteasome activity and potentially delay systemic muscle protein degradation in certain pathologic conditions.

키워드

과제정보

연구 과제 주관 기관 : Health Industry Development Institute, National Research Foundation

참고문헌

  1. Finley D, Ciechanover A, Varshavsky A. Ubiquitin as a central cellular regulator. Cell 2004; 116: S29-S32. https://doi.org/10.1016/S0092-8674(03)00971-1
  2. Pickart CM, Cohen RE. Proteasomes and their kin: proteases in the machine age. Nat Rev Mol Cell Biol 2004; 5: 177-187. https://doi.org/10.1038/nrm1336
  3. Baugh JM, Viktorova EG, Pilipenko EV. Proteasomes can degrade a significant proportion of cellular proteins independent of ubiquitination. J Mol Biol 2009; 386: 814-827. https://doi.org/10.1016/j.jmb.2008.12.081
  4. Pariat M, Carillo S, Molinari M, Salvat C, Debussche L, Bracco L et al. Proteolysis by calpains: a possible contribution to degradation of p53. Mol Cell Biol 1997; 17: 2806-2815. https://doi.org/10.1128/MCB.17.5.2806
  5. Taggart CC, Lowe GJ, Greene CM, Mulgrew AT, O'Neill SJ, Levine RL et al. Cathepsin B, L, and S cleave and inactivate secretory leucoprotease inhibitor. J Biol Chem 2001; 276: 33345-33352. https://doi.org/10.1074/jbc.M103220200
  6. Lee BH, Lee MJ, Park S, Oh DC, Elsasser S, Chen PC et al. Enhancement of proteasome activity by a small-molecule inhibitor of USP14. Nature 2010; 467: 179-184. https://doi.org/10.1038/nature09299
  7. Sies H. Oxidative stress: from basic research to clinical application. Am J Med 1991; 91: 31S-38S.
  8. Sies H. Oxidative stress: oxidants and antioxidants. Exp Physiol 1997; 82: 291-295. https://doi.org/10.1113/expphysiol.1997.sp004024
  9. Zhu X, Raina AK, Lee HG, Casadesus G, Smith MA, Perry G. Oxidative stress signalling in Alzheimer's disease. Brain Res 2004; 1000: 32-39. https://doi.org/10.1016/j.brainres.2004.01.012
  10. Goldberg AL. Protein degradation and protection against misfolded or damaged proteins. Nature 2003; 426: 895-899. https://doi.org/10.1038/nature02263
  11. Cuervo AM, Bergamini E, Brunk UT, Droge W, Ffrench M, Terman A. Autophagy and aging: the importance of maintaining 'clean' cells. Autophagy 2005; 1: 131-140. https://doi.org/10.4161/auto.1.3.2017
  12. Powers SK, Kavazis AN, DeRuisseau KC. Mechanisms of disuse muscle atrophy: role of oxidative stress. Am J Physiol Regul Integr Comp Physiol 2005; 288: R337-R344. https://doi.org/10.1152/ajpregu.00469.2004
  13. Lecker SH, Jagoe RT, Gilbert A, Gomes M, Baracos V, Bailey J et al. Multiple types of skeletal muscle atrophy involve a common program of changes in gene expression. FASEB J 2004; 18: 39-51. https://doi.org/10.1096/fj.03-0610com
  14. Solomon V, Baracos V, Sarraf P, Goldberg AL. Rates of ubiquitin conjugation increase when muscles atrophy, largely through activation of the N-end rule pathway. Proc Natl Acad Sci USA 1998; 95: 12602-12607. https://doi.org/10.1073/pnas.95.21.12602
  15. Jagoe RT, Goldberg AL. What do we really know about the ubiquitinproteasome pathway in muscle atrophy? Curr Opin Clin Nutr Metab Care 2001; 4: 183-190. https://doi.org/10.1097/00075197-200105000-00003
  16. Sala-Vila A, Calder PC. Update on the relationship of fish intake with prostate, breast, and colorectal cancers. Crit Rev Food Sci Nutr 2011; 51: 855-871. https://doi.org/10.1080/10408398.2010.483527
  17. MacLean CH, Newberry SJ, Mojica WA, Khanna P, Issa AM, Suttorp MJ et al. Effects of omega-3 fatty acids on cancer risk: a systematic review. JAMA 2006; 295: 403-415. https://doi.org/10.1001/jama.295.4.403
  18. Cornwell DG, Huttner JJ, Milo GE, Panganamala RV, Sharma HM, Geer JC. Polyunsaturated fatty acids, vitamin E, and the proliferation of aortic smooth muscle cells. Lipids 1979; 14: 194-207. https://doi.org/10.1007/BF02533871
  19. Huttner JJ, Gwebu ET, Panganamala RV, Milo GE, Cornwell DC, Sharma HM et al. Fatty acids and their prostaglandin derivatives: inhibitors of proliferation in aortic smooth muscle cells. Science 1977; 197: 289-291. https://doi.org/10.1126/science.877555
  20. Stadtman ER. Protein oxidation and aging. Free Radic Res 2006; 40: 1250-1258.
  21. Ding WQ, Lind SE. Phospholipid hydroperoxide glutathione peroxidase plays a role in protecting cancer cells from docosahexaenoic acid-induced cytotoxicity. Mol Cancer Ther 2007; 6: 1467-1474. https://doi.org/10.1158/1535-7163.MCT-06-0608
  22. Choi WH, de Poot SAH, Lee JH, Kim JH, Han DH, Kim YK et al. Open-gate mutants of the mammalian proteasome show enhanced ubiquitin-conjugate degradation. Nat Commun 2016; 7: 10963. https://doi.org/10.1038/ncomms10963
  23. Son YH, Lee SJ, Lee KB, Lee JH, Jeong EM, Chung SG et al. Dexamethasone downregulates caveolin-1 causing muscle atrophy via inhibited insulin signaling. J Endocrinol 2015; 225: 27-37. https://doi.org/10.1530/JOE-14-0490
  24. Wojcik C, Lohe K, Kuang C, Xiao Y, Jouni Z, Poels E. Modulation of adipocyte differentiation by omega-3 polyunsaturated fatty acids involves the ubiquitin-proteasome system. J Cell Mol Med 2014; 18: 590-599. https://doi.org/10.1111/jcmm.12194
  25. Zhang X, Zhou J, Fernandes AF, Sparrow JR, Pereira P, Taylor A et al. The proteasome: a target of oxidative damage in cultured human retina pigment epithelial cells. Invest Ophthalmol Vis Sci 2008; 49: 3622-3630. https://doi.org/10.1167/iovs.07-1559
  26. Lee JH, Jiang Y, Kwon YT, Lee MJ. Pharmacological Modulation of the N-End Rule Pathway and its Therapeutic Implications. Trends Pharmacol Sci 2015; 36: 782-797. https://doi.org/10.1016/j.tips.2015.07.004
  27. Jiang Y, Choi WH, Lee JH, Han DH, Kim JH, Chung YS et al. A neurostimulant para-chloroamphetamine inhibits the arginylation branch of the N-end rule pathway. Sci Rep 2014; 4: 6344.
  28. Jiang Y, Pore SK, Lee JH, Sriram S, Mai BK, Han DH et al. Characterization of mammalian N-degrons and development of heterovalent inhibitors of the N-end rule pathway. Chem Sci 2013; 4: 3339-3346. https://doi.org/10.1039/c3sc51059j
  29. Moreau KL, King JA. Protein misfolding and aggregation in cataract disease and prospects for prevention. Trends Mol Med 2012; 18: 273-282. https://doi.org/10.1016/j.molmed.2012.03.005
  30. McGreal RS, Kantorow WL, Chauss DC, Wei J, Brennan LA, Kantorow M. alphaB-crystallin/sHSP protects cytochrome c and mitochondrial function against oxidative stress in lens and retinal cells. Biochim Biophys Acta 2012; 1820: 921-930. https://doi.org/10.1016/j.bbagen.2012.04.004
  31. Hough R, Pratt G, Rechsteiner M. Purification of two high molecular weight proteases from rabbit reticulocyte lysate. J Biol Chem 1987; 262: 8303-8313.
  32. Lee JH, Shin SK, Jiang Y, Choi WH, Hong C, Kim DE et al. Facilitated Tau Degradation by USP14 Aptamers via Enhanced Proteasome Activity. Sci Rep 2015; 5: 10757. https://doi.org/10.1038/srep10757
  33. Finley D. Recognition and processing of ubiquitin-protein conjugates by the proteasome. Annu Rev Biochem 2009; 78: 477-513. https://doi.org/10.1146/annurev.biochem.78.081507.101607
  34. Kisselev AF, Callard A, Goldberg AL. Importance of the different proteolytic sites of the proteasome and the efficacy of inhibitors varies with the protein substrate. J Biol Chem 2006; 281: 8582-8590. https://doi.org/10.1074/jbc.M509043200
  35. Han DH, Na HK, Choi WH, Lee JH, Kim YK, Won C et al. Direct cellular delivery of human proteasomes to delay tau aggregation. Nat Commun 2014; 5: 5633. https://doi.org/10.1038/ncomms6633
  36. Mandelkow EM, Mandelkow E. Tau in Alzheimer's disease. Trends Cell Biol 1998; 8: 425-427. https://doi.org/10.1016/S0962-8924(98)01368-3
  37. Lee MJ, Lee JH, Rubinsztein DC. Tau degradation: the ubiquitinproteasome system versus the autophagy-lysosome system. Prog Neurobiol 2013; 105: 49-59. https://doi.org/10.1016/j.pneurobio.2013.03.001
  38. Bandyopadhyay B, Li G, Yin H, Kuret J. Tau aggregation and toxicity in a cell culture model of tauopathy. J Biol Chem 2007; 282: 16454-16464. https://doi.org/10.1074/jbc.M700192200
  39. Sahara N, Maeda S, Murayama M, Suzuki T, Dohmae N, Yen SH et al. Assembly of two distinct dimers and higher-order oligomers from full-length tau. Eur J Neurosci 2007; 25: 3020-3029. https://doi.org/10.1111/j.1460-9568.2007.05555.x
  40. Jing K, Song KS, Shin S, Kim N, Jeong S, Oh HR et al. Docosahexaenoic acid induces autophagy through p53/AMPK/mTOR signaling and promotes apoptosis in human cancer cells harboring wild-type p53. Autophagy 2011; 7: 1348-1358. https://doi.org/10.4161/auto.7.11.16658
  41. Tisdale MJ. The ubiquitin-proteasome pathway as a therapeutic target for muscle wasting. J Support Oncol 2005; 3: 209-217.
  42. Tisdale MJ. Mechanisms of cancer cachexia. Physiol Rev 2009; 89: 381-410. https://doi.org/10.1152/physrev.00016.2008
  43. Wigmore SJ, Barber MD, Ross JA, Tisdale MJ, Fearon KC. Effect of oral eicosapentaenoic acid on weight loss in patients with pancreatic cancer. Nutr Cancer 2000; 36: 177-184. https://doi.org/10.1207/S15327914NC3602_6
  44. Burns CP, Halabi S, Clamon GH, Hars V, Wagner BA, Hohl RJ et al. Phase I clinical study of fish oil fatty acid capsules for patients with cancer cachexia: cancer and leukemia group B study 9473. Clin Cancer Res 1999; 5: 3942-3947.
  45. Wigmore SJ, Ross JA, Falconer JS, Plester CE, Tisdale MJ, Carter DC et al. The effect of polyunsaturated fatty acids on the progress of cachexia in patients with pancreatic cancer. Nutrition 1996; 12: S27-S30. https://doi.org/10.1016/0899-9007(95)00078-X
  46. Tisdale MJ. Inhibition of lipolysis and muscle protein degradation by EPA in cancer cachexia. Nutrition 1996; 12: S31-S33. https://doi.org/10.1016/0899-9007(95)00066-6
  47. Vaughan VC, Hassing MR, Lewandowski PA. Marine polyunsaturated fatty acids and cancer therapy. Br J Cancer 2013; 108: 486-492. https://doi.org/10.1038/bjc.2012.586

피인용 문헌

  1. Inactivation of USP14 Perturbs Ubiquitin Homeostasis and Delays the Cell Cycle in Mouse Embryonic Fibroblasts and in Fruit Fly Drosophila vol.47, pp.1, 2018, https://doi.org/10.1159/000489750
  2. Degradation or aggregation: the ramifications of post-translational modifications on tau vol.51, pp.6, 2017, https://doi.org/10.5483/bmbrep.2018.51.6.077
  3. Sargassum serratifolium Extract Attenuates Interleukin-1β-Induced Oxidative Stress and Inflammatory Response in Chondrocytes by Suppressing the Activation of NF-κB, p38 MAPK, and PI3K/Akt vol.19, pp.8, 2017, https://doi.org/10.3390/ijms19082308
  4. Effect of dietary fish oil intake on ubiquitin ligase expression during muscle atrophy induced by sciatic nerve denervation in mice vol.90, pp.8, 2019, https://doi.org/10.1111/asj.13224
  5. Could Omega 3 Fatty Acids Preserve Muscle Health in Rheumatoid Arthritis? vol.12, pp.1, 2017, https://doi.org/10.3390/nu12010223
  6. Docosahexaenoic Acid, a Potential Treatment for Sarcopenia, Modulates the Ubiquitin–Proteasome and the Autophagy–Lysosome Systems vol.12, pp.9, 2017, https://doi.org/10.3390/nu12092597
  7. Proteasome Activity in the Plasma as a Novel Biomarker in Mild Cognitive Impairment with Chronic Tinnitus vol.78, pp.1, 2017, https://doi.org/10.3233/jad-200728
  8. Metabolism and pharmacokinetics of a novel polyphenol fatty acid ester phloridzin docosahexaenoate in Balb/c female mice vol.10, pp.1, 2020, https://doi.org/10.1038/s41598-020-78369-0
  9. Carpomitra costata Extract Suppresses Interleukin-1β-Induced Inflammatory Response in SW1353 Human Chondrocytes through Suppressing NF-κB Signaling Pathway vol.12, pp.2, 2017, https://doi.org/10.15433/ksmb.2020.12.2.099
  10. Cell Death via Lipid Peroxidation and Protein Aggregation Diseases vol.10, pp.5, 2017, https://doi.org/10.3390/biology10050399
  11. Docosahexaenoic Acid Inhibits Cytokine Expression by Reducing Reactive Oxygen Species in Pancreatic Stellate Cells vol.26, pp.3, 2017, https://doi.org/10.15430/jcp.2021.26.3.195