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

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

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

    subbiah pugazhenthiSubbiah Pugazhenthi,leonid akhovLeonid Akhov,gopalan selvarajGopalan Selvaraj,maorong wangMaorong Wang,jawed alamJawed Alam,

    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.

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

    s pugazhenthiS Pugazhenthi,l akhovL Akhov,g selvarajG Selvaraj,m wangM Wang,j alamJ Alam,

    For similar biological phenomena, cell phenomena, and immunity: cell physiology: cell communication: signal transduction research abstracts see: biological phenomena, cell phenomena, and immunity: cell physiology: cell communication: signal transduction research

    PUBMED ID PMID:

    MEDLINE DATE:

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

    PUBLICATION TYPE: Research Support, Non-U.S. Gov

    Journal: American journal of physiology. Endocrinology and

    VOLUME: 293

    Page Numbers: E645-55

    Journal Abbreviation: Am. J. Physiol. Endocrinol. Me

    ISSN: 0193-1849

    DAY: 29

    MONTH: 05

    YEAR: 2007

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

    Number of References:

    LANGUAGE: eng

    NlmUniqueID: 100901226

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

    KEYWORDS: Signal Transduction

    MESH TERMS: physiology

    Chemical & Substance for Abstract: Regulation of heme oxygenase-1 expression by demethoxy curcuminoids through Nrf2 by a PI3-kinase/Akt-mediated pathway in mouse beta-cells. Information

    Substance Name: Proto-Oncogene Proteins c-akt

    Registry Number: EC 2.7.1.37

    Grant and Affiliation Information for Regulation of heme oxygenase-1 expression by demethoxy curcuminoids through Nrf2 by a PI3-kinase/Akt-mediated pathway in mouse beta-cells.

    AFFILIATION: Department of Medicine, University of Colorado at Denver and Health Sciences Center, P.O. Box 6511, Mail Stop 8106, Aurora, CO 80045, USA. subbiah.pugazhenthi@uchsc.edu

    Country: United States

    United States Research PublicationUnited States Research Publication

    AGENCY: United States NIDDK

    GRANT: P30 DK-057516

    ACRONYM: DK

    MEDLINETA: Am J Physiol Endocrinol Metab

    REFSOURCE:

    DATABASENAME:

    ACCESSION NUMBER:

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

     

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