Transcriptional regulation of cytokines and oxidative stress by gallic acid in human THP-1 monocytes

Kuppan, G and Balasubramanyam, J and Monickaraj, Finny and Srinivasan, G and Mohan, V and Balasubramanyam, M (2010) Transcriptional regulation of cytokines and oxidative stress by gallic acid in human THP-1 monocytes. Cytokine, 49 (2). p. 229. ISSN 10434666

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Abstract

Increased inflammation/prooxidation has been linked not only to Type 2 diabetes but also in prediabetes state. In this study we investigated hyperglycemia-mediated proinflammatory/prooxidant effects in THP- 1 monocytes and tested whether gallic acid could attenuate changes in gene expression induced by highglucose. Cells were treated either with 5.5 mM glucose or 25 mM glucose in the absence and presence of gallic acid. While oxidative DNA damage was assessed by COMET assay, GSH and GSSG levels were estimated fluorimetrically. Gene expression patterns were determined by RT-PCR. Cells treated with high-glucose showed increased DNA damage and glutathione depletion and this was attenuated in the presence of gallic acid. High-glucose treated cells exhibited increased mRNA expression of TNF-a, IL-6, NADPH oxidase and TXNIP and gallic acid attenuated these proinflammatory and prooxidant effects. Cells treated with high-glucose revealed a deficiency in mounting SOCS-3 expression and gallic acid upregulates this feedback regulatory signal. Gallic acid attenuates DNA damage, maintains glutathione turnover, and suppresses hyperglycemia-induced activation of proinflammatory and prooxidant gene expression. Gallic acid beneficially modulate transcription of functionally diverse groups of genes and its regulation of SOCS-3 and TXNIP signals is a newly identified mechanism that has therapeutic implications.

Item Type:Article
Official URL/DOI:http://dx.doi.org/10.1016/j.cyto.2009.11.003
Uncontrolled Keywords:Gallic acid;THP-1 monocytes;Cytokines;TXNIP;SOCS-3
Subjects:Diabetes Epidemiology
Genetics and Diabetes
Biochemistry,Cell and Molecular Signalling
Divisions:Department of Cell and Molecular Biology
Neonatal Diabetes
Department of Diabetology
ID Code:441
Deposited By:INVALID USER
Deposited On:22 Jan 2010 08:54
Last Modified:22 Jan 2010 08:54

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