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Your search keyword '"Tegla CA"' showing total 2 results
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2 results on '"Tegla CA"'

1. SIRT1 is decreased during relapses in patients with multiple sclerosis.

Author

Tegla CA, Azimzadeh P, Andrian-Albescu M, Martin A, Cudrici CD, Trippe R 3rd, Sugarman A, Chen H, Boodhoo D, Vlaicu SI, Royal W 3rd, Bever C, Rus V, and Rus H

Subjects
Acetylation, Adolescent, Adult, Aged, Apoptosis genetics, Biomarkers metabolism, Brain metabolism, Cell Cycle Proteins metabolism, Cell Line, Female, Gene Expression Regulation, Histone Deacetylases metabolism, Histone Methyltransferases, Histone-Lysine N-Methyltransferase metabolism, Histones genetics, Humans, Leukocytes, Mononuclear pathology, Male, Middle Aged, Multiple Sclerosis blood, Multiple Sclerosis pathology, Muscle Proteins metabolism, Nerve Tissue Proteins metabolism, RNA, Messenger biosynthesis, Sirtuin 1 biosynthesis, Sirtuin 1 genetics, Brain pathology, Histones metabolism, Leukocytes, Mononuclear metabolism, Multiple Sclerosis genetics, Sirtuin 1 blood
Abstract

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., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Published
2014
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2. Dual role of Response gene to complement-32 in multiple sclerosis.

Author

Tegla CA, Cudrici CD, Azimzadeh P, Singh AK, Trippe R 3rd, Khan A, Chen H, Andrian-Albescu M, Royal W 3rd, Bever C, Rus V, and Rus H

Subjects
Actins metabolism, Adolescent, Adult, Aged, Antigens, CD analysis, Antigens, Differentiation, Myelomonocytic analysis, Apoptosis, Astrocytes metabolism, CD3 Complex analysis, Cell Cycle Proteins genetics, Cell Proliferation, Collagen Type I metabolism, Complement System Proteins metabolism, Cyclin D1 biosynthesis, Cyclin D1 genetics, Extracellular Matrix metabolism, Fas Ligand Protein genetics, Female, Fibronectins metabolism, Glial Fibrillary Acidic Protein, Humans, Interleukins biosynthesis, Interleukins genetics, Male, Middle Aged, Muscle Proteins genetics, Nerve Tissue Proteins genetics, Proto-Oncogene Proteins c-akt biosynthesis, Proto-Oncogene Proteins c-akt genetics, RNA Interference, RNA, Messenger genetics, RNA, Messenger metabolism, RNA, Small Interfering, T-Lymphocytes metabolism, Transforming Growth Factor beta metabolism, Young Adult, Interleukin-21, Brain metabolism, Cell Cycle Proteins metabolism, Leukocytes, Mononuclear metabolism, Multiple Sclerosis, Relapsing-Remitting metabolism, Muscle Proteins metabolism, Nerve Tissue Proteins metabolism
Abstract

Response gene to complement (RGC)-32 is a novel molecule that plays an important role in cell proliferation. We investigated the expression of RGC-32 in multiple sclerosis (MS) brain and in peripheral blood mononuclear cells (PBMCs) obtained from patients with relapsing-remitting multiple sclerosis. We found that CD3(+), CD68(+), and glial fibrillar acidic protein (GFAP)(+) cells in MS plaques co-localized with RGC-32. Our results show a statistically significant decrease in RGC-32 mRNA expression in PBMCs during relapses when compared to the levels in stable MS patients. This decrease might be useful in predicting disease activity in patients with relapsing-remitting MS. RGC-32 expression was also correlated with that of FasL mRNA during relapses. FasL mRNA expression was significantly reduced after RGC-32 silencing, indicating a role for RGC-32 in the regulation of FasL expression. In addition, the expression of Akt1, cyclin D1, and IL-21 mRNA was significantly increased during MS relapses when compared to levels in healthy controls. Furthermore, we investigated the role of RGC-32 in TGF-β-induced extracellular matrix expression in astrocytes. Blockage of RGC-32 using small interfering RNA significantly inhibits TGF-β induction of procollagen I, fibronectin and of the reactive astrocyte marker α-smooth muscle actin (α-SMA). Our data suggest that RGC-32 plays a dual role in MS, both as a regulator of T-cells mediated apoptosis and as a promoter of TGF-β-mediated profibrotic effects in astrocytes., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Published
2013
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