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학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
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연구자들이 자신의 연구와 전문성을 널리 알리고, 새로운 협력의 기회를 만들 수 있는 네트워킹 공간이에요.
논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2018.1
- 수록면
- 446 - 457 (12page)
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Adiponectin, a hormone predominantly originated from adipose tissue, has exhibited potent anti-inflammatory properties. Accumulating evidence suggests that autophagy induction plays a crucial role in anti-inflammatory responses by adiponectin. However, underlying molecular mechanisms are still largely unknown. Association of Bcl-2 with Beclin-1, an autophagy activating protein, prevents autophagy induction. We have previously shown that adiponectin-induced autophagy activation is mediated through inhibition of interaction between Bcl-2 and Beclin-1. In the present study, we examined the molecular mechanisms by which adiponectin modulates association of Bcl-2 and Beclin-1 in macrophages. Herein, we demonstrated that globular adiponectin (gAcrp) induced increase in the expression of AUF1 and ZFP36L1, which act as mRNA destabilizing proteins, both in RAW 264.7 macrophages and primary peritoneal macrophages. In addition, gene silencing of AUF1 and ZFP36L1 caused restoration of decrease in Bcl-2 expression and Bcl-2 mRNA half-life by gAcrp, indicating crucial roles of AUF1 and ZFP36L1 induction in Bcl-2 mRNA destabilization by gAcrp. Moreover, knock-down of AUF1 and ZFP36L1 enhanced interaction of Bcl-2 with Beclin-1, and subsequently prevented gAcrp-induced autophagy activation, suggesting that AUF1 and ZFP36L1 induction mediates gAcrp-induced autophagy activation via Bcl-2 mRNA destabilization. Furthermore, suppressive effects of gAcrp on LPS-stimulated inflammatory mediators expression were prevented by gene silencing of AUF1 and ZFP36L1 in macrophages. Taken together, these results suggest that AUF1 and ZFP36L1 induction critically contributes to autophagy induction by gAcrp and are promising targets for anti-inflammatory responses by gAcrp.
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참고문헌 (45)
참고문헌 신청
Blackshear, P. J. / 2002 / Tristetraprolin and other CCCH tandem zincfinger proteins in the regulation of mRNA turnover / Biochem. Soc. Trans. 30:945~952
Dalamaga, M. / 2012 / The role of adiponectin in cancer: a review of current evidence / Endocr. Rev. 33:547~594
Denzel, M. S. / 2010 / T-cadherin is critical for adiponectinmediated cardioprotection in mice / J. Clin. Invest. 120:4342~4352
Deretic, V. / 2013 / Autophagy in infection, inflammation and immunity / Nat. Rev. Immunol. 13:722~737
Dodson, R. E. / 2002 / Regulation of pathways of mRNA destabilization and stabilization / Prog. Nucleic Acid Res. Mol. Biol. 72:129~164
Dalamaga, M. / 2012 / The role of adiponectin in cancer: a review of current evidence / Endocr. Rev. 33:547~594
Denzel, M. S. / 2010 / T-cadherin is critical for adiponectinmediated cardioprotection in mice / J. Clin. Invest. 120:4342~4352
Deretic, V. / 2013 / Autophagy in infection, inflammation and immunity / Nat. Rev. Immunol. 13:722~737
Dodson, R. E. / 2002 / Regulation of pathways of mRNA destabilization and stabilization / Prog. Nucleic Acid Res. Mol. Biol. 72:129~164
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