Practical approaches to investigate redox regulation of heat shock protein expression and intracellular glutathione redox state

Vittorio Calabrese, Anna Signorile, Carolin Cornelius, Cesare Mancuso, Giovanni Scapagnini, Bernardo Ventimiglia, Nicolo Ragusa, Albena Dinkova-Kostova

    Research output: Chapter in Book/Report/Conference proceedingOther chapter contribution

    32 Citations (Scopus)

    Abstract

    The products of vitagenes such as heat shock protein 32 (Hsp32, heme oxygenase 1) and Hsp70, the family of inducible cytoprotective proteins regulated by the Keap1/Nrf2/ARE pathway, and small molecule antioxidants such as glutathione provide the cell with powerful means to counteract and survive various conditions of stress. Among these protective systems, the heat shock proteins represent a highly conserved and robust way for preservation of correct protein conformation, recovery of damaged proteins, and cell survival. Their regulation is dependent on the redox status of the cell, thus redox regulation is rapidly evolving as an important metabolic modulator of cellular functions, and is being increasingly implicated in many chronic inflammatory and degenerative diseases. Protein thiols play a key role in redox sensing, and regulation of cellular redox state is crucial mediator of multiple metabolic, signalling and transcriptional processes in the brain. Nitric oxide, and reactive nitrogen species induce the transcription of vitagenes and Keap1/Nrf2/ARE-dependent genes whose functional products protect against a wide array of subsequent challenges. Emerging interest is now focusing on exogenous small molecules that are capable of activating these systems as a novel target to minimize deleterious consequences associated with free radical-induced cell damage, such as during neurodegeneration. This chapter describes methods that can be used to assess the expression of heat shock proteins and the cellular glutathione redox status and discusses their relevance to mechanisms modulating the onset and progression of neurodegenerative diseases.

    Original languageEnglish
    Title of host publicationNitric oxide, Part G oxidative and nitrosative stress in redox regulation of cell signaling
    EditorsEnrique Cadenas, Lester Packer
    Place of PublicationSan Diego
    PublisherAcademic Press
    Pages83-110
    Number of pages28
    ISBN (Print)9780123743091
    DOIs
    Publication statusPublished - 2008

    Publication series

    NameMethods in Enzymology
    PublisherAcademic Press
    Volume441

    Keywords

    • NITRIC-OXIDE SYNTHASE
    • CELLULAR STRESS-RESPONSE
    • KAPPA-B ACTIVATION
    • HEME OXYGENASE-1 INDUCTION
    • COLORECTAL-CARCINOMA CELLS
    • VASCULAR ENDOTHELIAL-CELLS
    • HSP70 GENE-EXPRESSION
    • RAT GLIAL-CELLS
    • OXIDATIVE-STRESS
    • NEURODEGENERATIVE DISORDERS

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