The evaluation of gene expression and enzyme activity of SIRT1 in peripheral blood mononuclear cells isolated from patients with relapsing-remitting multiple sclerosis
Archives of Medical Laboratory Sciences,
Vol. 2 No. 1 (2016),
9 April 2016
https://doi.org/10.22037/amls.v2i1.11927
Abstract
Background: Little in known regarding the clinical relevance of SIRT1 in multiple sclerosis (MS). Here, we aimed to evaluate mRNA expression, protein level and enzyme activity of SIRT1 in peripheral blood mononuclear cells (PBMCs) isolated from relapsing –remitting MS patients (RRMS) and healthy controls.
Materials and Methods: Twenty patients with RR-MS and twenty two age- and sex-matched healthy subjects were enrolled in this case-control study. Following PBMCs isolation, mRNA expression was evaluated by real time-PCR. SIRT1 activity and SIRT1 protein level were measured using a fluorometric assay and an enzyme-linked immunosorbent assay (ELISA) respectively, in PBMC lysates.
Results: There was no statistically significant difference in the mRNA expression of SIRT1 (p=0.56) and its protein levels (p=0.15) between MS patients and healthy subjects. By contrast, SIRT1 enzyme activity were significantly (p=0.008) lower in RRMS patients compared with that in healthy subjects.
Conclusion: Our findings demonstrated that enzyme activity of SIRT1 is significantly lower in PBMCs of RRMS patients in comparison with healthy subjects. However, more investigations are essential to clarify the role of SIRT1 in MS pathogenesis.
- enzyme activity
- multiple sclerosis
- pathogenesis
How to Cite
References
Gonsette RE. Neurodegeneration in multiple sclerosis: the role of oxidative stress and excitotoxicity. J Neurol Sci. 2008 Nov 15;274(1-2):48-53.
Tullman MJ. Overview of the epidemiology, diagnosis, and disease progression associated with multiple sclerosis. Am J Manag Care. 2013;19(2 Suppl):S15-20.
Lublin FD, Reingold SC, Cohen JA, Cutter GR, Sørensen PS, Thompson AJ, et al. Defining the clinical course of multiple sclerosis The 2013 revisions. Neurology. 2014;83(3):278-86.
Zhang J, Lee SM, Shannon S, Gao B, Chen W, Chen A, et al. The type III histone deacetylase Sirt1 is essential for maintenance of T cell tolerance in mice. J Clin Invest. 2009 Oct;119(10):3048-58.
Zhang F, Wang S, Gan L, Vosler PS, Gao Y, Zigmond MJ, et al. Protective effects and mechanisms of sirtuins in the nervous system. Prog Neurobiol. 2011;95(3):373-95.
Zhang T, Kraus WL. SIRT1-dependent regulation of chromatin and transcription: linking NAD(+) metabolism and signaling to the control of cellular functions. Biochim Biophys Acta. 2010;1804(8):1666-75.
Yamamoto H, Schoonjans K, Auwerx J. Sirtuin functions in health and disease. Mol Endocrinol. 2007;21(8):1745-55.
Shindler KS, Ventura E, Dutt M, Elliott P, Fitzgerald DC, Rostami A. Oral resveratrol reduces neuronal damage in a model of multiple sclerosis. J Neuroophthalmol. 2010;30(4):328-39.
Shindler KS, Ventura E, Rex TS, Elliott P, Rostami A. SIRT1 activation confers neuroprotection in experimental optic neuritis. Invest Ophthalmol Vis Sci. 2007;48(8):3602-9.
Khan RS, Dine K, Das Sarma J, Shindler KS. SIRT1 activating compounds reduce oxidative stress mediated neuronal loss in viral induced CNS demyelinating disease. Acta Neuropathol Commun. 2014;2:3.
Nimmagadda VK, Bever CT, Vattikunta NR, Talat S, Ahmad V, Nagalla NK, et al. Overexpression of SIRT1 protein in neurons protects against experimental autoimmune encephalomyelitis through activation of multiple SIRT1 targets. J Immunol. 2013;190(9):4595-607.
Pallàs M, Casadesús G, Smith MA, Coto-Montes A, Pelegri C, Vilaplana J, et al. Resveratrol and neurodegenerative diseases: activation of SIRT1 as the potential pathway towards neuroprotection. Current neurovascular research. 2009;6(1):70-81.
Tegla CA, Azimzadeh P, Andrian-Albescu M, Martin A, Cudrici CD, Trippe R, 3rd, et al. SIRT1 is decreased during relapses inpatients with multiple sclerosis. Exp Mol Pathol. 2014 Apr;96(2):139-48.
Schmittgen TD, Livak KJ. Analyzing real-time PCR data by the comparative C(T) method. Nat Protoc. 2008;3(6):1101-8.
Pennisi G, Cornelius C, Cavallaro MM, Salinaro AT, Cambria MT, Pennisi M, et al. Redox regulation of cellular stress response in multiple sclerosis. Biochem Pharmacol. 2011 Nov 15;82(10):1490-9.
Nakagawa T, Guarente L. Sirtuins at a glance. J Cell Sci. 2011;124(Pt 6):833-8.
Martin A, Tegla CA, Cudrici CD, Kruszewski AM, Azimzadeh P, Boodhoo D, et al. Role of SIRT1 in autoimmune demyelination and neurodegeneration. Immunol Res. 2014 Oct 4.
Kauppinen A, Suuronen T, Ojala J, Kaarniranta K, Salminen A. Antagonistic crosstalk between NF-κB and SIRT1 in the regulation of inflammation and metabolic disorders. Cellular signalling. 2013;25(10):1939-48.
van Horssen J, Drexhage JA, Flor T, Gerritsen W, van der Valk P, de Vries HE. Nrf2 and DJ1 are consistently upregulated in inflammatory multiple sclerosis lesions. Free Radic Biol Med. 2010 Nov 1;49(8):1283-9.
Van der Goes A, Wouters D, Van Der Pol SM, Huizinga R, Ronken E, Adamson P, et al. Reactive oxygen species enhance the migration of monocytes across the blood-brain barrier in vitro. FASEB J. 2001;15(10):1852-4.
Yao H, Sundar IK, Ahmad T, Lerner C, Gerloff J, Friedman AE, et al. SIRT1 protects against cigarette smoke-induced lung oxidative stress via a FOXO3-dependent mechanism. Am J Physiol Lung Cell Mol Physiol. 2014;306(9):L816-28.
Chong ZZ, Shang YC, Wang S, Maiese K. SIRT1: new avenues of discovery for disorders of oxidative stress. Expert Opin Ther Targets. 2012;16(2):167-78.
Caito S, Rajendrasozhan S, Cook S, Chung S, Yao H, Friedman AE, et al. SIRT1 is a redox-sensitive deacetylase that is post-translationally modified by oxidants and carbonyl stress. FASEB J. 2010;24(9):3145-59.
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