title: Loss of Parkin reduces inflammatory arthritis by inhibiting p53 degradation.
abstract: 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-κB 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.
authors.affiliation: College of Pharmacy and Medical Research Center, Chungbuk National University, Osongsaengmyeong 1-ro 194-31, Osong-eup, Heungduk-gu, Cheongju, Chungbuk 361-951, Republic of Korea; Department of Dental Hygiene, Gwangyang Health Sciences University, Gwnagyang, Jeonnam 57764, Korea.
authors.forename: Yu Yeon
authors.initials: YY
authors.lastname: Jung
authors.affiliation: College of Pharmacy and Medical Research Center, Chungbuk National University, Osongsaengmyeong 1-ro 194-31, Osong-eup, Heungduk-gu, Cheongju, Chungbuk 361-951, Republic of Korea.
authors.forename: Dong Ju
authors.initials: DJ
authors.lastname: Son
authors.affiliation: College of Pharmacy and Medical Research Center, Chungbuk National University, Osongsaengmyeong 1-ro 194-31, Osong-eup, Heungduk-gu, Cheongju, Chungbuk 361-951, Republic of Korea.
authors.forename: Hye Lim
authors.initials: HL
authors.lastname: Lee
authors.affiliation: College of Pharmacy and Medical Research Center, Chungbuk National University, Osongsaengmyeong 1-ro 194-31, Osong-eup, Heungduk-gu, Cheongju, Chungbuk 361-951, Republic of Korea.
authors.forename: Dae Hwan
authors.initials: DH
authors.lastname: Kim
authors.affiliation: Department of Obstetrics and Gynecology, Daejeon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 64 Daeheung-ro, Jung-gu, Daejeon, Republic of Korea.
authors.forename: Min Jong
authors.initials: MJ
authors.lastname: Song
authors.affiliation: Department of Chemistry and Biochemistry, Brigham Young University, Provo, UT, United States.
authors.forename: Young Wan
authors.initials: YW
authors.lastname: Ham
authors.affiliation: College of Pharmacy and Medical Research Center, Chungbuk National University, Osongsaengmyeong 1-ro 194-31, Osong-eup, Heungduk-gu, Cheongju, Chungbuk 361-951, Republic of Korea.
authors.forename: Youngsoo
authors.initials: Y
authors.lastname: Kim
authors.affiliation: College of Pharmacy and Medical Research Center, Chungbuk National University, Osongsaengmyeong 1-ro 194-31, Osong-eup, Heungduk-gu, Cheongju, Chungbuk 361-951, Republic of Korea.
authors.forename: Sang Bae
authors.initials: SB
authors.lastname: Han
authors.affiliation: College of Pharmacy and Medical Research Center, Chungbuk National University, Osongsaengmyeong 1-ro 194-31, Osong-eup, Heungduk-gu, Cheongju, Chungbuk 361-951, Republic of Korea. Electronic address: pmh5205@hanmail.net.
authors.forename: Mi Hee
authors.initials: MH
authors.lastname: Park
authors.affiliation: College of Pharmacy and Medical Research Center, Chungbuk National University, Osongsaengmyeong 1-ro 194-31, Osong-eup, Heungduk-gu, Cheongju, Chungbuk 361-951, Republic of Korea. Electronic address: jinthong@chungbuk.ac.kr.
authors.forename: Jin Tae
authors.initials: JT
authors.lastname: Hong
mesh_terms: D000818:Animals; D001172:Arthritis, Rheumatoid / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004195:Disease Models, Animal; D057809:HEK293 Cells; D006801:Humans; D008070:Lipopolysaccharides / Q000009:adverse effects*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D016328:NF-kappa B / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D011485:Protein Binding; D059748:Proteolysis; D000067996:RAW 264.7 Cells; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D008070:Lipopolysaccharides; D016328:NF-kappa B; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D044767:Ubiquitin-Protein Ligases; C111567:parkin protein
keywords: Arthritis; Parkin; Ubiquitination; p53