NDLI: Resveratrol inhibits PDGF receptor mitogenic signaling in mesangial cells: role of PTP1B

Content Provider	PubMed Central
Author	Venkatesan, Balachandar Nandini, Ghosh-choudhury Das, Falguni Lenin, Mahimainathan Kamat, Amrita Kasinath, Balakuntalam S. Abboud, Hanna E. Choudhury, Goutam Ghosh
Copyright Year	2008
Abstract	Mesangioproliferative glomerulonephritis is associated with overactive PDGF receptor signal transduction. We show that the phytoalexin resveratrol dose dependently inhibits PDGF-induced DNA synthesis in mesangial cells with an IC50 of 10 μM without inducing apoptosis. Remarkably, the increased SIRT1 deacetylase activity induced by resveratrol was not necessary for this inhibitory effect. Resveratrol significantly blocked PDGF-stimulated c-Src and Akt kinase activation, resulting in reduced cyclin D1 expression and attenuated pRb phosphorylation and cyclin-dependent kinase-2 (CDK2) activity. Furthermore, resveratrol inhibited PDGFR phosphorylation at the PI 3 kinase and Grb-2 binding sites tyrosine-751 and tyrosine-716, respectively. This deficiency in PDGFR phosphorylation resulted in significant inhibition of PI 3 kinase and Erk1/2 MAPK activity. Interestingly, resveratrol increased the activity of protein tyrosine phosphatase PTP1B, which dephosphorylates PDGF-stimulated phosphorylation at tyrosine-751 and tyrosine-716 on PDGFR with concomitant reduction in Akt and Erk1/2 kinase activity. PTP1B significantly inhibited PDGF-induced DNA synthesis without inducing apoptosis. These results for the first time provide evidence that the stilbene resveratrol targets PTP1B to inhibit PDGFR mitogenic signaling.—Venkatesan, B., Ghosh-Choudhury, N., Das, F., Mahimainathan, L., Kamat, A., Kasinath, B. S., Abboud, H. E., Choudhury, G. G. Resveratrol inhibits PDGF receptor mitogenic signaling in mesangial cells: role of PTP1B.
Related Links	http://dx.doi.org/10.1096/fj.08-109488
Ending Page	3482
Page Count	14
Starting Page	3469
File Format	PDF
ISSN	08926638
e-ISSN	15306860
Journal	The FASEB Journal
Issue Number	10
Volume Number	22
Language	English
Publisher	The Federation of American Societies for Experimental Biology
Publisher Date	2008-06-01
Access Restriction	Open
Rights Holder	The Federation of American Societies for Experimental Biology
Subject Keyword	Biotechnology Genetics Biochemistry Molecular Biology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Genetics Medicine Molecular Biology Biochemistry Biotechnology

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