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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
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- 2017.1
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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.
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참고문헌 (27)
참고문헌 신청
Baugh JM / 2009 / Proteasomes can degrade a significant proportion of cellular proteins independent of ubiquitination / J Mol Biol 386 : 814 ~ 827
Choi WH / 2016 / Nat Commun / Nat Commun 7 : 10963 ~
Cornwell DG / 1979 / Polyunsaturated fatty acids, vitamin E, and the proliferation of aortic smooth muscle cells / Lipids 14 : 194 ~ 207
Cuervo AM / 2005 / Autophagy and aging: the importance of maintaining ‘clean’ cells / Autophagy 1 : 131 ~ 140
Ding WQ / 2007 / Phospholipid hydroperoxide glutathione peroxidase plays a role in protecting cancer cells from docosahexaenoic acid-induced cytotoxicity / Mol Cancer Ther 6
Choi WH / 2016 / Nat Commun / Nat Commun 7 : 10963 ~
Cornwell DG / 1979 / Polyunsaturated fatty acids, vitamin E, and the proliferation of aortic smooth muscle cells / Lipids 14 : 194 ~ 207
Cuervo AM / 2005 / Autophagy and aging: the importance of maintaining ‘clean’ cells / Autophagy 1 : 131 ~ 140
Ding WQ / 2007 / Phospholipid hydroperoxide glutathione peroxidase plays a role in protecting cancer cells from docosahexaenoic acid-induced cytotoxicity / Mol Cancer Ther 6
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