Article

Differential activation of catalase expression and activity by PPAR agonists: Implications for astrocyte protection in anti-glioma therapy

Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA.
Redox biology 01/2013; 1(1):70-9. DOI: 10.1016/j.redox.2012.12.006
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ABSTRACT Glioma survival is dismal, in part, due to an imbalance in antioxidant expression and activity. Peroxisome proliferator-activated receptor (PPAR) agonists have antineoplastic properties which present new redox-dependent targets for glioma anticancer therapies. Herein, we demonstrate that treatment of primary cultures of normal rat astrocytes with PPAR agonists increased the expression of catalase mRNA protein, and enzymatic activity. In contrast, these same agonists had no effect on catalase expression and activity in malignant rat glioma cells. The increase in steady-state catalase mRNA observed in normal rat astrocytes was due, in part, to de novo mRNA synthesis as opposed to increased catalase mRNA stability. Moreover, pioglitazone-mediated induction of catalase activity in normal rat astrocytes was completely blocked by transfection with a PPARγ-dominant negative plasmid. These data suggest that defects in PPAR-mediated signaling and gene expression may represent a block to normal catalase expression and induction in malignant glioma. The ability of PPAR agonists to differentially increase catalase expression and activity in normal astrocytes but not glioma cells suggests that these compounds might represent novel adjuvant therapeutic agents for the treatment of gliomas.

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Available from: Frederick E Domann, Apr 14, 2014
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    • "Redox signaling and cell death is represented by an interesting paper suggesting that histone modifications are mediated by oxidative stress [20] and in another paper an exploration of the mechanisms of arsenite toxicity [21]. Hydrogen peroxide, its regulation and signaling are linked to PPAR and some of the mechanisms of its interaction with superoxide dismutase are described in papers [22] [23]. "
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