Cell biology international
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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. ⋯ 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.