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Calreticulin transacetylase catalyzed modification of the TNF-alpha mediated pathway in the human peripheral blood mononuclear cells by polyphenolic acetates.

Abstract：

:Polyphenols, coumarin (1,2-benzopyrone) and chromone (1,4-benzopyrone), are naturally occurring constituent of variety of plant species. They have attracted immense interest because of their diverse pharmacological activities. Not much was known about biological activities of acetyl derivative (polyphenolic acetates) of parent polyphenols. In previous investigations, we have conclusively established calreticulin transacetylase catalyzed activation of endothelial nitric oxide synthase (eNOS) by polyphenolic acetates. In the present work, calreticulin transacetylase of human peripheral blood mononuclear cells was characterized with respect to specificity for various polyphenolic acetates and its role in the activation of TNF-alpha induced nitric oxide synthase (iNOS). Peripheral blood mononuclear cells incubated with a model polyphenolic acetate, 7,8-diacetoxy-4-methylcoumarin (DAMC), along with L-arginine caused activation of NOS. The incubation of peripheral blood mononuclear cells with TNF-alpha and DAMC resulted in increased production of NO as compared to TNF-alpha alone. This increased NO production was attenuated by l-Nomega-nitro-L-arginine methyl ester (L-NAME), a well known non-specific inhibitor of NOS, and 1400W (N-[3-(aminomethyl) benzyl] acetamidine), a specific inhibitor of human iNOS. These results substantiate the CRTAase catalyzed activation of iNOS. Further, expression of NOS isoforms by semi-quantitative PCR and real-time RT-PCR confirms the preponderance of iNOS in TNF-alpha treated peripheral blood mononuclear cells over the untreated one. It was also observed that polyphenolic acetates inhibit TNF-alpha mediated release of IL-6 from peripheral blood mononuclear cells.

journal_name

Chem Biol Interact

journal_title

Chemico-biological interactions

authors

Singh U,Kumar A,Sinha R,Manral S,Arora S,Ram S,Mishra RK,Gupta P,Bansal SK,Prasad AK,Biswal S,Parmar VS,Raj HG

doi

10.1016/j.cbi.2010.02.025

subject

Has Abstract

pub_date

2010-05-14 00:00:00

pages

263-70

issue

eissn

0009-2797

issn

1872-7786

pii

S0009-2797(10)00093-1

journal_volume

185

pub_type

杂志文章

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Calreticulin transacetylase catalyzed modification of the TNF-alpha mediated pathway in the human peripheral blood mononuclear cells by polyphenolic acetates.