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Plumbagin Inhibits Proliferative and Inflammatory Responses of T Cells Independent of ROS Generation But by Modulating Intracellular Thiols

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Title Plumbagin Inhibits Proliferative and Inflammatory Responses of T Cells Independent of ROS Generation But by Modulating Intracellular Thiols
 
Creator CHECKER, R
SHARMA, D
SANDUR, SK
SUBRAHMANYAM, G
KRISHNAN, S
PODUVAL, TB
SAINIS, KB
 
Subject nf-kappa-b
homeostasis driven proliferation
regulated gene-products
oxidative stress
alpha kinase
mediated inhibition
s-glutathionylation
cysteine residues
in-vitro
lymphocytes
anti-inflammatory
[hio]
redox
immune
plumbagin
glutathionylation
 
Description Plumbagin inhibited activation, proliferation, cytokine production, and graft-versus-host disease in lymphocytes and inhibited growth of tumor cells by suppressing nuclear factor-kappa B (NF-kappa B). Plumbagin was also shown to induce reactive oxygen species (ROS) generation in tumor cells via an unknown mechanism Present report describes a novel role of cellular redox in modulation of immune responses in normal lymphocytes by plumbagin. Plumbagin depleted glutathione (GSH) levels that led to increase in ROS generation The decrease in GSH levels was due to direct reaction of plumbagin with GSH as evinced by mass spectrometric and HPLC analysis. Further, addition of plumbagin to cells resulted in decrease in free thiol groups on proteins and increase in glutathionylation of proteins. The suppression of mitogen-induced T-cell proliferation and cytokine (IL-2/IL-4/IL-6/IFN-gamma) production by plumbagin was abrogated by thiol antioxidants but not by non-thiol antioxidants confirming that thiols but not ROS play an important role in biological activity of plumbagin. Plumbagin also abrogated mitogen-induced phosphorylation of ERK, IKK, and degradation of I kappa B-alpha However, it did not affect phosphorylation of P38, JNK, and AKT. Our results for the first time show that antiproliferative effects of plumbagin are mediated by modulation of cellular redox These results provide a rationale for application of thiol-depleting agents as anti-inflammatory drugs J. Cell Biochem. 110: 1082-1093, 2010. (C) 2010 Wiley-Liss. Inc
 
Publisher WILEY-LISS
 
Date 2011-09-01T13:38:00Z
2011-12-26T12:59:40Z
2011-12-27T05:52:18Z
2011-09-01T13:38:00Z
2011-12-26T12:59:40Z
2011-12-27T05:52:18Z
2010
 
Type Article
 
Identifier JOURNAL OF CELLULAR BIOCHEMISTRY, 110(5), 1082-1093
0730-2312
http://dx.doi.org/10.1002/jcb.22620
http://dspace.library.iitb.ac.in/xmlui/handle/10054/12792
http://hdl.handle.net/10054/12792
 
Language en