AJP - Endo Fuel your research with LabChart
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Am J Physiol Endocrinol Metab 293: E645-E655, 2007. First published May 29, 2007; doi:10.1152/ajpendo.00111.2007
0193-1849/07 $8.00
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
293/3/E645    most recent
00111.2007v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via ISI Web of Science (5)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Pugazhenthi, S.
Right arrow Articles by Alam, J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Pugazhenthi, S.
Right arrow Articles by Alam, J.

Regulation of heme oxygenase-1 expression by demethoxy curcuminoids through Nrf2 by a PI3-kinase/Akt-mediated pathway in mouse beta-cells

Subbiah Pugazhenthi,1 Leonid Akhov,2 Gopalan Selvaraj,2 Maorong Wang,1 and Jawed Alam3

1Division of Endocrinology, Metabolism and Diabetes, Department of Medicine, University of Colorado at Denver and Health Sciences Center, Aurora; and Section of Endocrinology, Veterans Affairs Medical Center, Denver, Colorado; 2Plant Biotechnology Institute, Saskatoon, Saskatchewan, Canada; and 3Department of Molecular Genetics, Ochsner Medical Center, New Orleans, Louisiana

Submitted 17 January 2007 ; accepted in final form 28 May 2007

Curcumin (diferuloylmethane), a component of turmeric, has been shown to have therapeutic properties. Induction of phase 2 detoxifying enzymes is a potential mechanism through which some of the actions of curcumin could proceed. Heme oxygenase-1 (HO-1), an antioxidant phase 2 enzyme, has been reported to have cytoprotective effects in pancreatic beta-cells. Curcumin on further purification yields demethoxy curcumin (DMC) and bisdemethoxy curcumin (BDMC). The objective of the present study was to determine the mechanism by which these purified curcuminoids induce HO-1 in MIN6 cells, a mouse beta-cell line. Demethoxy curcuminoids induced HO-1 promoter linked to the luciferase reporter gene more effectively than curcumin. The induction was dependent on the presence of antioxidant response element (ARE) sites containing enhancer regions (E1 and E2) in HO-1 promoter and nuclear translocation of nuclear factor-E2-related factor (Nrf2), the transcription factor that binds to ARE. Curcuminoids stimulated multiple signaling pathways that are known to induce HO-1. Inhibition of specific signaling pathways with pharmacological inhibitors and cotransfection experiments suggested the involvement of phosphotidylinositol 3-kinase and Akt. Real-time quantitative RT-PCR analysis showed significant elevation in the mRNA levels of HO-1 and two other phase 2 enzymes, the regulatory subunit of glutamyl cysteine ligase, which is needed for the synthesis of glutathione, and NAD(P)H:quinone oxidoreductase, which detoxifies quinones. DMC and BDMC induced the expression of HO-1 and translocated Nrf2 to nucleus in beta-cells of mouse islets. Our observations suggest that demethoxy curcuminoids could be used to induce a cellular defense mechanism in beta-cells under conditions of stress as seen in diabetes.

phase 2 enzymes; diabetes; pancreatic beta-cells; oxidative stress


Address for reprint requests and other correspondence: S. Pugazhenthi, Div. of Endocrinology, Metabolism and Diabetes, Dept. of Medicine, Univ. of Colorado at Denver and Health Sciences Center, P.O. Box 6511, Mail Stop 8106, Aurora, CO 80045 (e-mail: subbiah.pugazhenthi{at}uchsc.edu)




This article has been cited by other articles:


Home page
 Clin. Cancer Res.Home page
D. Wang, M. S. Veena, K. Stevenson, C. Tang, B. Ho, J. D. Suh, V. M. Duarte, K. F. Faull, K. Mehta, E. S. Srivatsan, et al.
Liposome-Encapsulated Curcumin Suppresses Growth of Head and Neck Squamous Cell Carcinoma In vitro and in Xenografts through the Inhibition of Nuclear Factor {kappa}B by an AKT-Independent Pathway
Clin. Cancer Res., October 1, 2008; 14(19): 6228 - 6236.
[Abstract] [Full Text] [PDF]

Home page
 CarcinogenesisHome page
M. B. Sibhatu, P. K. Smitherman, A. J. Townsend, and C. S. Morrow
Expression of MRP1 and GSTP1-1 modulate the acute cellular response to treatment with the chemopreventive isothiocyanate, sulforaphane
Carcinogenesis, April 1, 2008; 29(4): 807 - 815.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
L. Zhu, J. Pi, S. Wachi, M. E. Andersen, R. Wu, and Y. Chen
Identification of Nrf2-dependent airway epithelial adaptive response to proinflammatory oxidant-hypochlorous acid challenge by transcription profiling
Am J Physiol Lung Cell Mol Physiol, March 1, 2008; 294(3): L469 - L477.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Visit Other APS Journals Online
Copyright © 2007 by the American Physiological Society.