title: SIRT1 inhibits apoptosis of degenerative human disc nucleus pulposus cells through activation of Akt pathway.
abstract: Many studies have demonstrated that SIRT1, an NAD(+)-dependent deacetylase, reduces apoptosis in several different cells. However, the role of SIRT1 in apoptosis of disc nucleus pulposus (NP) cells remains unclear. The present study was performed to determine whether degenerative human NP would express SIRT1, and to investigate the role of SIRT1 in NP cells apoptosis. The expression of SIRT1 in disc NP of patients (>55 years) with lumbar disc degenerative disease (DDD) and the disc NP of patients (<25 years) with lumbar vertebra fracture (LVF) was assessed by immunohistochemistry, reverse transcription polymerase chain reaction, and Western blot analysis. The results showed that SIRT1 mRNA and protein levels were greater in LVF disc NP than those in DDD disc NP. Degenerative human NP cells were treated in culture with activator or inhibitor of SIRT1, resveratrol or nicotinamide, or SIRT1 small interfering RNA (siRNA), and cell apoptosis was quantified via flow cytometry. The rate of apoptosis was far fewer in resveratrol-treated NP cells than in SIRT1 siRNA-transfected or nicotinamide-treated NP cells. After SIRT1 siRNA was transfected, NP cells decreased phosphorylation of Akt, while resveratrol phosphorylated Akt. Treatment with LY294002 or Akt siRNA increased the rate of apoptosis. Our results suggested that SIRT1 plays a critical role in survival of degenerative human NP cells through the Akt anti-apoptotic signaling pathway.
authors.affiliation: Department of Orthopedic Surgery, The First Affiliated Hospital of Chongqing Medical University, 1 Youyi Rd, Yuzhong District, Chongqing, 400016, China.
authors.forename: DaWu
authors.initials: D
authors.lastname: Wang
authors.forename: ZhenMing
authors.initials: Z
authors.lastname: Hu
authors.forename: Jie
authors.initials: J
authors.lastname: Hao
authors.forename: Bin
authors.initials: B
authors.lastname: He
authors.forename: Qiang
authors.initials: Q
authors.lastname: Gan
authors.forename: XiaoMing
authors.initials: X
authors.lastname: Zhong
authors.forename: XiaoJun
authors.initials: X
authors.lastname: Zhang
authors.forename: JieLiang
authors.initials: J
authors.lastname: Shen
authors.forename: Ji
authors.initials: J
authors.lastname: Fang
authors.forename: Wei
authors.initials: W
authors.lastname: Jiang
mesh_terms: D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000235:genetics*; D015153:Blotting, Western; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D055959:Intervertebral Disc Degeneration / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D008159:Lumbar Vertebrae / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D051057:Proto-Oncogene Proteins c-akt / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D000077185:Resveratrol; D012264:Ribonucleotide Reductases / Q000037:antagonists & inhibitors; D015398:Signal Transduction / Q000502:physiology; D056564:Sirtuin 1 / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics*; D013267:Stilbenes / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D004791:Enzyme Inhibitors; D012333:RNA, Messenger; D013267:Stilbenes; D012264:Ribonucleotide Reductases; D051057:Proto-Oncogene Proteins c-akt; C447939:SIRT1 protein, human; D056564:Sirtuin 1; D000077185:Resveratrol