title: Inhibitory effects of SRT1720 on the apoptosis of rabbit chondrocytes by activating SIRT1 via p53/bax and NF-κB/PGC-1α pathways.
abstract: SRT1720, a new discovered drug, was reported to activate silent information regulator 1 (SIRT1) and inhibit the chondrocyte apoptosis. However, the underlying mechanism remains elusive. In the present study, the chondrocytes were extracted from the cartilage tissues of New Zealand white rabbits, cultured in the presence of sodium nitroprusside (SNP) (2.5 mmol/L) and divided into five groups: 1, 5, 10, and 20 μmol/L SRT1720 groups and blank control group (0 μmol/L SRT1720). MTT assay was used to detect the chondrocyte viability and proliferation, and DAPI staining and flow cytometry to measure the chondrocyte apoptosis. The expression levels of SIRT1, p53, NF-κB/p65, Bax, and peroxisome proliferator-activated receptor gamma coactivator 1-α (PGC-1α) were detected by Western blotting and the expression levels of SIRT1, type II collagen, and aggrecan mRNA by RT-PCR. The results showed that in the SRT1720-treated groups, the nuclei of chondrocytes were morphologically intact and had uniform chromatin. In the blank control group, nuclear rupture into debris was observed in chondrocytes. With the SRT1720 concentration increasing, the chondrocyte viability increased, the apoptosis rate decreased, the protein expression levels of SIRT1 and PGC-1α and the mRNA expression levels of type II collagen and aggrecan increased ({ptP}<0.05), and the expression levels of p53, NF-κB and bax decreased (P<0.05). It was suggested that SRT1720 inhibits chondrocyte apoptosis by activating the expression of SIRT1 via p53/bax and NF-κB/PGC-1α pathways.
authors.affiliation: Central Laboratory, Peking University Shenzhen Hospital, Shenzhen, 518000, China.|Shenzhen Luohu People's Hospital, Guangzhou Medical University, Shenzhen, 518000, China.
authors.forename: Bi
authors.initials: B
authors.lastname: Liu
authors.affiliation: Central Laboratory, Peking University Shenzhen Hospital, Shenzhen, 518000, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Lei
authors.affiliation: Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Hu
authors.affiliation: Central Laboratory, Peking University Shenzhen Hospital, Shenzhen, 518000, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Yu
authors.affiliation: Central Laboratory, Peking University Shenzhen Hospital, Shenzhen, 518000, China. xiaodeming-1956@163.com.
authors.forename: De-Ming
authors.initials: DM
authors.lastname: Xiao
authors.affiliation: Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. kanghao1112@126.com.
authors.forename: Hao
authors.initials: H
authors.lastname: Kang
mesh_terms: D053674:Aggrecans / Q000235:genetics / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002358:Cartilage, Articular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D019902:Chondrocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D002843:Chromatin / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D024043:Collagen Type II / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D006576:Heterocyclic Compounds, 4 or More Rings / Q000494:pharmacology*; D009599:Nitroprusside / Q000633:toxicity; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / Q000235:genetics / Q000378:metabolism; D061251:Primary Cell Culture; D011817:Rabbits; D015398:Signal Transduction / Q000187:drug effects* / Q000235:genetics; D056564:Sirtuin 1 / Q000235:genetics* / Q000378:metabolism; D051996:Transcription Factor RelA / Q000235:genetics / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D053674:Aggrecans; D002843:Chromatin; D024043:Collagen Type II; D006576:Heterocyclic Compounds, 4 or More Rings; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C525422:SRT1720; D051996:Transcription Factor RelA; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D009599:Nitroprusside; D056564:Sirtuin 1
keywords: SIRT1; SRT1720; apoptosis; chondrocyte