PMID- 24397908 OWN - NLM STAT- MEDLINE DCOM- 20140528 LR - 20201214 IS - 1096-0945 (Electronic) IS - 0014-4800 (Linking) VI - 96 IP - 2 DP - 2014 Apr TI - SIRT1 is decreased during relapses in patients with multiple sclerosis. PG - 139-48 LID - S0014-4800(13)00156-1 [pii] LID - 10.1016/j.yexmp.2013.12.010 [doi] AB - SIRT1 is a member of the histone deacetylase (HDAC) class III family of proteins and is an NAD-dependent histone and protein deacetylase. SIRT1 can induce chromatin silencing through the deacetylation of histones and can modulate cell survival by regulating the transcriptional activities. We investigated the expression of SIRT1 in multiple sclerosis (MS) brains and in peripheral blood mononuclear cells (PBMCs) obtained from patients with relapsing-remitting multiple sclerosis. We found that SIRT1 was expressed by a significant number of cells in both acute and chronic active lesions. We also found that CD4(+), CD68(+), oligodendrocytes (OLG), and glial fibrillar acidic protein (GFAP)(+) cells in MS plaques co-localized with SIRT1. Our results show a statistically significant decrease in SIRT1 mRNA and protein expression in PBMCs during relapses when compared to the levels in controls and stable MS patients. On the other hand, HDAC3 expression was not significantly changed during relapses in MS patients. SIRT1 expression correlated with that of histone H3 lysine 9 acetylation (H3K9ac) and methylation (H3K9me2). SIRT1 mRNA expression was significantly reduced after RGC-32 silencing, indicating a role for RGC-32 in the regulation of SIRT1 expression. Furthermore, we investigated the role of SIRT1 in the expression of FasL and found a significant increase in FasL expression and apoptosis after inhibition of SIRT1 expression. Our data suggest that SIRT1 may represent a biomarker of relapses and a potential new target for therapeutic intervention in MS. CI - Copyright (c) 2014 Elsevier Inc. All rights reserved. FAU - Tegla, Cosmin A AU - Tegla CA AD - Research Service, Veterans Administration Maryland Health Care System, Baltimore, MD, USA; Department of Neurology, University of Maryland, School of Medicine, Baltimore, MD, USA. FAU - Azimzadeh, Philippe AU - Azimzadeh P AD - Department of Neurology, University of Maryland, School of Medicine, Baltimore, MD, USA. FAU - Andrian-Albescu, Maria AU - Andrian-Albescu M AD - Department of Neurology, University of Maryland, School of Medicine, Baltimore, MD, USA. FAU - Martin, Alvaro AU - Martin A AD - Department of Neurology, University of Maryland, School of Medicine, Baltimore, MD, USA. FAU - Cudrici, Cornelia D AU - Cudrici CD AD - Department of Neurology, University of Maryland, School of Medicine, Baltimore, MD, USA. FAU - Trippe, Richard 3rd AU - Trippe R 3rd AD - Department of Neurology, University of Maryland, School of Medicine, Baltimore, MD, USA. FAU - Sugarman, Adam AU - Sugarman A AD - Department of Neurology, University of Maryland, School of Medicine, Baltimore, MD, USA. FAU - Chen, Hegang AU - Chen H AD - Department of Epidemiology and Public Health, University of Maryland, School of Medicine, Baltimore, MD, USA. FAU - Boodhoo, Dallas AU - Boodhoo D AD - Department of Neurology, University of Maryland, School of Medicine, Baltimore, MD, USA. FAU - Vlaicu, Sonia I AU - Vlaicu SI AD - Department of Neurology, University of Maryland, School of Medicine, Baltimore, MD, USA. FAU - Royal, Walter 3rd AU - Royal W 3rd AD - Department of Neurology, University of Maryland, School of Medicine, Baltimore, MD, USA; Veterans Administration Multiple Sclerosis Center of Excellence, Baltimore, MD, USA. FAU - Bever, Christopher AU - Bever C AD - Department of Neurology, University of Maryland, School of Medicine, Baltimore, MD, USA; Research Service, Veterans Administration Maryland Health Care System, Baltimore, MD, USA; Veterans Administration Multiple Sclerosis Center of Excellence, Baltimore, MD, USA. FAU - Rus, Violeta AU - Rus V AD - Department of Medicine, Division of Rheumatology and Clinical Immunology, University of Maryland, School of Medicine, Baltimore, MD, USA. FAU - Rus, Horea AU - Rus H AD - Department of Neurology, University of Maryland, School of Medicine, Baltimore, MD, USA; Research Service, Veterans Administration Maryland Health Care System, Baltimore, MD, USA; Veterans Administration Multiple Sclerosis Center of Excellence, Baltimore, MD, USA. Electronic address: hrus@umaryland.edu. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20140105 PL - Netherlands TA - Exp Mol Pathol JT - Experimental and molecular pathology JID - 0370711 RN - 0 (Biomarkers) RN - 0 (Cell Cycle Proteins) RN - 0 (Histones) RN - 0 (Muscle Proteins) RN - 0 (Nerve Tissue Proteins) RN - 0 (RGCC protein, human) RN - 0 (RNA, Messenger) RN - EC 2.1.1.- (Histone Methyltransferases) RN - EC 2.1.1.43 (Histone-Lysine N-Methyltransferase) RN - EC 3.5.1.- (SIRT1 protein, human) RN - EC 3.5.1.- (Sirtuin 1) RN - EC 3.5.1.98 (Histone Deacetylases) RN - EC 3.5.1.98 (histone deacetylase 3) SB - IM MH - Acetylation MH - Adolescent MH - Adult MH - Aged MH - Apoptosis/genetics MH - Biomarkers/metabolism MH - Brain/metabolism/*pathology MH - Cell Cycle Proteins/metabolism MH - Cell Line MH - Female MH - Gene Expression Regulation MH - Histone Deacetylases/metabolism MH - Histone Methyltransferases MH - Histone-Lysine N-Methyltransferase/metabolism MH - Histones/genetics/*metabolism MH - Humans MH - Leukocytes, Mononuclear/*metabolism/pathology MH - Male MH - Middle Aged MH - Multiple Sclerosis/blood/*genetics/pathology MH - Muscle Proteins/metabolism MH - Nerve Tissue Proteins/metabolism MH - RNA, Messenger/biosynthesis MH - Sirtuin 1/biosynthesis/*blood/genetics OTO - NOTNLM OT - Acetylation OT - Biomarker OT - Epigenetics OT - HDAC3 OT - Multiple sclerosis OT - Peripheral blood mononuclear cells OT - RGC-32 OT - SIRT1 EDAT- 2014/01/09 06:00 MHDA- 2014/05/29 06:00 CRDT- 2014/01/09 06:00 PHST- 2013/12/19 00:00 [received] PHST- 2013/12/27 00:00 [accepted] PHST- 2014/01/09 06:00 [entrez] PHST- 2014/01/09 06:00 [pubmed] PHST- 2014/05/29 06:00 [medline] AID - S0014-4800(13)00156-1 [pii] AID - 10.1016/j.yexmp.2013.12.010 [doi] PST - ppublish SO - Exp Mol Pathol. 2014 Apr;96(2):139-48. doi: 10.1016/j.yexmp.2013.12.010. Epub 2014 Jan 5.