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Acetylcarnitine induces heme oxygenase in rat astrocytes and protects against oxidative stress: involvement of the transcription factor Nrf2.
J Neurosci Res 2005; 79(4):509-21JN

Abstract

Efficient functioning of maintenance and repair processes seem to be crucial for both survival and physical quality of life. This is accomplished by a complex network of the so-called longevity assurance processes, under control of several genes termed vitagenes. These include members of the heat shock protein system, and there is now evidence that the heat shock response contributes to establishing a cytoprotective state in a wide variety of human conditions, including inflammation, neurodegenerative disorders, and aging. Among the various heat shock proteins, heme oxygenase-1 has received considerable attention; it has been recently demonstrated that heme oxygenase-1 induction, by generating the vasoactive molecule carbon monoxide and the potent antioxidant bilirubin, could represent a protective system potentially active against brain oxidative injury. Acetyl-L-carnitine is proposed as a therapeutic agent for several neurodegenerative disorders. Accordingly, we report here that treatment of astrocytes with acetyl-L-carnitine induces heme oxygenase-1 in a dose- and time-dependent manner and that this effect was associated with up-regulation of heat shock protein 60 as well as high expression of the redox-sensitive transcription factor Nrf2 in the nuclear fraction of treated cells. In addition, we show that addition of acetyl-L-carnitine to astrocytes, prior to proinflammatory lipopolysaccharide- and interferon-gamma-induced nitrosative stress, prevents changes in mitochondrial respiratory chain complex activity, protein nitrosation and antioxidant status induced by inflammatory cytokine insult. Given the broad cytoprotective properties of the heat shock response, molecules inducing this defense mechanism appear to be possible candidates for novel cytoprotective strategies. Particularly, manipulation of endogenous cellular defense mechanisms via acetyl-L-carnitine may represent an innovative approach to therapeutic intervention in diseases causing tissue damage, such as neurodegeneration. We hypothesize that maintenance or recovery of the activity of vitagenes may delay the aging process and decrease the risk of age-related diseases.

Authors+Show Affiliations

Department of Chemistry, Biochemistry and Molecular Biology Section, Faculty of Medicine, University of Catania, Catania, Italy. calabres@mbox.unict.itNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

15641110

Citation

Calabrese, Vittorio, et al. "Acetylcarnitine Induces Heme Oxygenase in Rat Astrocytes and Protects Against Oxidative Stress: Involvement of the Transcription Factor Nrf2." Journal of Neuroscience Research, vol. 79, no. 4, 2005, pp. 509-21.
Calabrese V, Ravagna A, Colombrita C, et al. Acetylcarnitine induces heme oxygenase in rat astrocytes and protects against oxidative stress: involvement of the transcription factor Nrf2. J Neurosci Res. 2005;79(4):509-21.
Calabrese, V., Ravagna, A., Colombrita, C., Scapagnini, G., Guagliano, E., Calvani, M., ... Giuffrida Stella, A. M. (2005). Acetylcarnitine induces heme oxygenase in rat astrocytes and protects against oxidative stress: involvement of the transcription factor Nrf2. Journal of Neuroscience Research, 79(4), pp. 509-21.
Calabrese V, et al. Acetylcarnitine Induces Heme Oxygenase in Rat Astrocytes and Protects Against Oxidative Stress: Involvement of the Transcription Factor Nrf2. J Neurosci Res. 2005 Feb 15;79(4):509-21. PubMed PMID: 15641110.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Acetylcarnitine induces heme oxygenase in rat astrocytes and protects against oxidative stress: involvement of the transcription factor Nrf2. AU - Calabrese,Vittorio, AU - Ravagna,Agrippino, AU - Colombrita,Claudia, AU - Scapagnini,Giovanni, AU - Guagliano,Eleonora, AU - Calvani,Menotti, AU - Butterfield,D Allan, AU - Giuffrida Stella,Anna Maria, PY - 2005/1/11/pubmed PY - 2005/4/19/medline PY - 2005/1/11/entrez SP - 509 EP - 21 JF - Journal of neuroscience research JO - J. Neurosci. Res. VL - 79 IS - 4 N2 - Efficient functioning of maintenance and repair processes seem to be crucial for both survival and physical quality of life. This is accomplished by a complex network of the so-called longevity assurance processes, under control of several genes termed vitagenes. These include members of the heat shock protein system, and there is now evidence that the heat shock response contributes to establishing a cytoprotective state in a wide variety of human conditions, including inflammation, neurodegenerative disorders, and aging. Among the various heat shock proteins, heme oxygenase-1 has received considerable attention; it has been recently demonstrated that heme oxygenase-1 induction, by generating the vasoactive molecule carbon monoxide and the potent antioxidant bilirubin, could represent a protective system potentially active against brain oxidative injury. Acetyl-L-carnitine is proposed as a therapeutic agent for several neurodegenerative disorders. Accordingly, we report here that treatment of astrocytes with acetyl-L-carnitine induces heme oxygenase-1 in a dose- and time-dependent manner and that this effect was associated with up-regulation of heat shock protein 60 as well as high expression of the redox-sensitive transcription factor Nrf2 in the nuclear fraction of treated cells. In addition, we show that addition of acetyl-L-carnitine to astrocytes, prior to proinflammatory lipopolysaccharide- and interferon-gamma-induced nitrosative stress, prevents changes in mitochondrial respiratory chain complex activity, protein nitrosation and antioxidant status induced by inflammatory cytokine insult. Given the broad cytoprotective properties of the heat shock response, molecules inducing this defense mechanism appear to be possible candidates for novel cytoprotective strategies. Particularly, manipulation of endogenous cellular defense mechanisms via acetyl-L-carnitine may represent an innovative approach to therapeutic intervention in diseases causing tissue damage, such as neurodegeneration. We hypothesize that maintenance or recovery of the activity of vitagenes may delay the aging process and decrease the risk of age-related diseases. SN - 0360-4012 UR - https://www.unboundmedicine.com/medline/citation/15641110/Acetylcarnitine_induces_heme_oxygenase_in_rat_astrocytes_and_protects_against_oxidative_stress:_involvement_of_the_transcription_factor_Nrf2_ L2 - https://doi.org/10.1002/jnr.20386 DB - PRIME DP - Unbound Medicine ER -