title: SIRT1 expression is refractory to hypoxia and inflammatory cytokines in nucleus pulposus cells: Novel regulation by HIF-1α and NF-κB signaling.
abstract: Hypoxia and a marked increase in inflammatory cytokines are common hallmarks of intervertebral disc degeneration; these events disrupt the normal balance between extracellular matrix (ECM) degradation and synthesis in degenerative intervertebral discs. SIRT1, one of the NAD+-dependent class III histone deacetylases, controls cellular processes and is regulated by hypoxia and inflammatory cytokines in a cell-type-dependent manner. SIRT1 protects degenerative human nucleus pulposus cells against apoptosis. However, the role of SIRT1 in inflammation in intervertebral discs is still unclear. The current study showed that in rat NP cells, as in other cells, SIRT1 suppressed the induction of the mRNA expression of proteases that degrade ECM induced by TNF-α. Moreover, real-time PCR, transfection, and loss- and gain-of-function experiments revealed that SIRT1 mRNA and protein expression were refractory to hypoxia and HIF-1α. Additionally, SIRT1 mRNA and protein expression and the activity of the SIRT1 promoter were not affected by inflammatory cytokines but were sustained by NF-κB signaling in the presence or absence of TNF-α. In summary, the present study suggested that SIRT1 is not affected by hypoxia and inflammatory cytokines in rat intervertebral discs. Moreover, not HIF-1α but NF-κB signaling is critical for the maintenance of SIRT1 expression in NP cells under physiologic and pathophysiologic conditions.
authors.affiliation: Department of Spine Surgery, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Spine Surgery, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, China.|Department of Orthopedics, First People's Hospital of Yunnan Province, Kunming, China.
authors.forename: Hongjian
authors.initials: H
authors.lastname: Li
authors.affiliation: Experimental Center of Surgery, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Kang
authors.initials: K
authors.lastname: Xu
authors.affiliation: Department of Spine Surgery, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Haipeng
authors.initials: H
authors.lastname: Zhu
authors.affiliation: Department of Spine Surgery, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Peng
authors.affiliation: Department of Spine Surgery, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Anjing
authors.initials: A
authors.lastname: Liang
authors.affiliation: Department of Spine Surgery, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Chunhai
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Spine Surgery, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Dongsheng
authors.initials: D
authors.lastname: Huang
authors.affiliation: Department of Spine Surgery, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Ye
mesh_terms: D000818:Animals; D015687:Cell Hypoxia / Q000502:physiology; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D055959:Intervertebral Disc Degeneration / Q000378:metabolism / Q000628:therapy; D016328:NF-kappa B / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D000070614:Nucleus Pulposus / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction; D056564:Sirtuin 1 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D016207:Cytokines; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D016328:NF-kappa B; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; C488368:Sirt1 protein, rat; D056564:Sirtuin 1
keywords: HIF-1α; IL-1β; NF-κB signaling; SIRT1; TNF-α; intervertebral disc degeneration