Loss of Parkin reduces inflammatory arthritis by inhibiting p53 degradation

被引：26

作者：

Jung, Yu Yeon ^{[1
,2
,3
]}

Son, Dong Ju ^{[1
,2
]}

Lee, Hye Lim ^{[1
,2
]}

Kim, Dae Hwan ^{[1
,2
]}

Song, Min Jong ^{[4
]}

Ham, Young Wan ^{[5
]}

Kim, Youngsoo ^{[1
,2
]}

Han, Sang Bae ^{[1
,2
]}

Park, Mi Hee ^{[1
,2
]}

Hong, Jin Tae ^{[1
,2
]}

机构：

[1] Chungbuk Natl Univ, Coll Pharm, Osongsaengmyeong 1 Ro 194-31, Cheongju 361951, Chungbuk, South Korea

[2] Chungbuk Natl Univ, Med Res Ctr, Osongsaengmyeong 1 Ro 194-31, Cheongju 361951, Chungbuk, South Korea

[3] Gwangyang Hlth Sci Univ, Dept Dent Hyg, Gwnagyang 57764, Jeonnam, South Korea

[4] Catholic Univ Korea, Daejeon St Marys Hosp, Dept Obstet & Gynecol, Coll Med, 64 Daeheung Ro, Daejeon, South Korea

[5] Brigham Young Univ, Dept Chem & Biochem, Provo, UT 84602 USA

来源：

REDOX BIOLOGY | 2017年 / 12卷

基金：

新加坡国家研究基金会;

关键词：

Parkin; Arthritis; p53; Ubiquitination; UBIQUITIN-PROTEIN LIGASE; TUMOR-SUPPRESSOR; RHEUMATOID-ARTHRITIS; KAPPA-B; MEDIATED MITOPHAGY; DISEASE; ACTIVATION; REPRESSION; MUTATIONS; REGULATOR;

D O I：

10.1016/j.redox.2017.04.007

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Parkin is associated with various inflammatory diseases, including Parkinson's disease (PD) and rheumatoid arthritis (RA). However, the precise role of Parkin in RA is unclear. The present study addressed this issue by comparing the development of RA between non-transgenic (non-Tg) mice and PARK2 knockout (KO) mice. We found that cyclooxygenase-2 and inducible nitric oxide synthase expression and nuclear factor-kappa B activity were reduced but p53 activation was increased in PARK2 KO as compared to non-Tg mice. These effects were associated with reduced p53 degradation. Parkin was found to interact with p53; however, this was abolished in Parkin KO mice, which prevented p53 degradation. Treatment of PARK2 KO mice with p53 inhibitor increased Parkin expression as well as inflammation and RA development while decreasing nuclear p53 translocation, demonstrating that PARK2 deficiency inhibits inflammation in RA via suppression of p53 degradation. These results suggest that RA development may be reduced in PD patients.

引用

页码：666 / 673

页数：8

共 35 条

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