Oxidative DNA damage and augmentation of poly(ADP-ribose) polymerase/nuclear factor-kappa B signaling in patients with Type 2 diabetes and microangiopathy

Adaikalakoteswari, A. ORCID: 0000-0003-2974-3388, Rema, M., Mohan, V. and Balasubramanyam, M., 2007. Oxidative DNA damage and augmentation of poly(ADP-ribose) polymerase/nuclear factor-kappa B signaling in patients with Type 2 diabetes and microangiopathy. The International Journal of Biochemistry & Cell Biology, 39 (9), pp. 1673-1684. ISSN 1357-2725

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Abstract

Although oxidative stress and the subsequent DNA damage is one of the obligatory signals for poly(ADP-ribose) polymerase (PARP) activation and nuclear factor-kappa B (NFκB) alterations, these molecular aspects have not been collectively examined in epidemiological and clinical settings. Therefore, this study attempts to assess the oxidative DNA damage and its downstream effector signals in peripheral blood lymphocytes from Type 2 diabetes subjects without and with microangiopathy along with age-matched non-diabetic subjects. The basal DNA damage, lipid peroxidation and protein carbonyl content were significantly (p < 0.05) higher in patients with and without microangiopathy compared to control subjects. Formamido Pyrimidine Glycosylase (FPG)-sensitive DNA strand breaks which represents reliable indicator of oxidative DNA damage were also significantly (p < 0.001) higher in diabetic patients with (19.41 ± 2.5) and without microangiopathy (16.53 ± 2.0) compared to control subjects (1.38 ± 0.85). Oxidative DNA damage was significantly correlated to poor glycemic control. PARP mRNA expression and PARP activity were significantly (p < 0.05) increased in cells from diabetic patients with (0.31 ± 0.03 densitometry units; 0.22 ± 0.02 PARP units/mg protein, respectively) and without (0.35 ± 0.02; 0.42 ± 0.05) microangiopathy compared to control (0.19 ± 0.02; 0.11 ± 0.02) subjects. Diabetic subjects with and without microangiopathy exhibited a significantly (p < 0.05) higher (80%) NFκB binding activity compared to control subjects. In diabetic patients, FPG-sensitive DNA strand breaks correlated positively with PARP gene expression, PARP activity and NFκB binding activity. This study provides a comprehensive molecular evidence for increased oxidative stress and genomic instability in Type 2 diabetic subjects even prior to vascular pathology and hence reveals a window of opportunity for early therapeutic intervention.

Item Type: Journal article
Publication Title: The International Journal of Biochemistry & Cell Biology
Creators: Adaikalakoteswari, A., Rema, M., Mohan, V. and Balasubramanyam, M.
Publisher: Elsevier
Date: 2007
Volume: 39
Number: 9
ISSN: 1357-2725
Identifiers:
NumberType
10.1016/j.biocel.2007.04.013DOI
S135727250700129XPublisher Item Identifier
Rights: Copyright © 2007 Elsevier Ltd. All rights reserved.
Divisions: Schools > School of Science and Technology
Depositing User: Linda Sullivan
Date Added: 04 May 2018 11:42
Last Modified: 04 May 2018 11:42
URI: http://irep.ntu.ac.uk/id/eprint/33443

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