Histone Deacetylase SIRT1 Mediates C5b-9-Induced Cell Cycle in Oligodendrocytes
Date
2020Journal
Frontiers in ImmunologyPublisher
Frontiers Media S.A.Type
Article
Metadata
Show full item recordAbstract
Sublytic levels of C5b-9 increase the survival of oligodendrocytes (OLGs) and induce the cell cycle. We have previously observed that SIRT1 co-localizes with surviving OLGs in multiple sclerosis (MS) plaques, but it is not yet known whether SIRT1 is involved in OLGs survival after exposure to sublytic C5b-9. We have now investigated the role of SIRT1 in OLGs differentiation and the effect of sublytic levels of C5b-9 on SIRT1 and phosphorylated-SIRT1 (Ser27) expression. We also examined the downstream effects of SIRT1 by measuring histone H3 lysine 9 trimethylation (H3K9me3) and the expression of cyclin D1 as a marker of cell cycle activation. OLG progenitor cells (OPCs) purified from the brain of rat pups were differentiated in vitro and treated with sublytic C5b-9 or C5b6. To investigate the signaling pathway activated by C5b-9 and required for SIRT1 expression, we pretreated OLGs with a c-jun antisense oligonucleotide, a phosphoinositide 3-kinase (PI3K) inhibitor (LY294002), and a protein kinase C (PKC) inhibitor (H7). Our data show a significant reduction in phospho-SIRT1 and SIRT1 expression during OPCs differentiation, associated with a decrease in H3K9me3 and a peak of cyclin D1 expression in the first 24 h. Stimulation of OLGs with sublytic C5b-9 resulted in an increase in the expression of SIRT1 and phospho-SIRT1, H3K9me3, cyclin D1 and decreased expression of myelin-specific genes. C5b-9-stimulated SIRT1 expression was significantly reduced after pretreatment with c-jun antisense oligonucleotide, H7 or LY294002. Inhibition of SIRT1 with sirtinol also abolished C5b-9-induced DNA synthesis. Taken together, these data show that induction of SIRT1 expression by C5b-9 is required for cell cycle activation and is mediated through multiple signaling pathways. Copyright 2020 Tatomir, et. al.Sponsors
This work was supported in part Veterans Administration Merit Award I01BX001458 and RO1 NS42011.Identifier to cite or link to this item
https://www.scopus.com/inward/record.uri?eid=2-s2.0-85083899682&doi=10.3389%2ffimmu.2020.00619&partnerID=40&md5=9496d331526f226656869073dd3f5ca2; http://hdl.handle.net/10713/12766ae974a485f413a2113503eed53cd6c53
10.3389/fimmu.2020.00619
Scopus Count
Collections
Related articles
- Terminal complement complexes induce cell cycle entry in oligodendrocytes through mitogen activated protein kinase pathway.
- Authors: Rus H, Niculescu F, Badea T, Shin ML
- Issue date: 1997 Dec
- C5b-9-activated, K(v)1.3 channels mediate oligodendrocyte cell cycle activation and dedifferentiation.
- Authors: Tegla CA, Cudrici C, Rozycka M, Soloviova K, Ito T, Singh AK, Khan A, Azimzadeh P, Andrian-Albescu M, Khan A, Niculescu F, Rus V, Judge SI, Rus H
- Issue date: 2011 Aug
- Inhibition of oligodendrocyte apoptosis by sublytic C5b-9 is associated with enhanced synthesis of bcl-2 and mediated by inhibition of caspase-3 activation.
- Authors: Soane L, Rus H, Niculescu F, Shin ML
- Issue date: 1999 Dec 1
- Sublytic C5b-9-stimulated Schwann cell survival through PI 3-kinase-mediated phosphorylation of BAD.
- Authors: Hila S, Soane L, Koski CL
- Issue date: 2001 Oct
- Sublytic complement attack induces cell cycle in oligodendrocytes.
- Authors: Rus HG, Niculescu F, Shin ML
- Issue date: 1996 Jun 15