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

Nicholas K.H Khoo; Sachin Hebbar; Weiling Zhao; Steven A Moore; Frederick E Domann; Mike E Robbins

doi:10.1016/j.redox.2012.12.006

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

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

Nicholas K.H Khoo, Sachin Hebbar, Weiling Zhao, Steven A Moore, Frederick E Domann and Mike E Robbins

Redox biology, Vol.1(1), pp.70-79

2013

DOI: 10.1016/j.redox.2012.12.006

PMCID: PMC3757675

PMID: 24024139

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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.

GSH, glutathione

PPAR agonists

RXR, retinoid X receptor

9cRA, 9 cis retinoic acid

C6 glioma cells

Transfection

Catalase

PPAR, Peroxisome proliferator-activated receptor

Research Paper

GPx, glutathione peroxidase

Rosi, Rosiglitazone

PPRE, PPAR-response elements

ROS, reactive oxygen species

Pio, Pioglitazone

BCNU, 1,3-bis (2-chloroethyl)-1-nitrosourea

TZDs, thiazolidinediones

SOD, superoxide dismutase

DCF, dichlorofluorescein

PUFAs, polyunsaturated fatty acids

CNS, central nervous system

PPARγ-dominant negative

Primary rat astrocytes

PPARγ-d.n, PPARγ-dominant negative

shRNA, short hairpin RNA

ActD, actinomycin D

Details

Title: Subtitle: Differential activation of catalase expression and activity by PPAR agonists: Implications for astrocyte protection in anti-glioma therapy
Creators: Nicholas K.H Khoo - Department of Radiation Oncology, Free Radical and Radiation Biology, Holden Comprehensive Cancer Center, The University of Iowa, Iowa City, IA 52242, USA
Sachin Hebbar - Department of Radiation Oncology, Comprehensive Cancer Center of Wake Forest University, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA
Weiling Zhao - Department of Radiation Oncology, Comprehensive Cancer Center of Wake Forest University, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA
Steven A Moore - Department of Pathology, Holden Comprehensive Cancer Center, The University of Iowa, Iowa City, IA 52242, USA
Frederick E Domann - Department of Radiation Oncology, Free Radical and Radiation Biology, Holden Comprehensive Cancer Center, The University of Iowa, Iowa City, IA 52242, USA
Mike E Robbins - Department of Radiation Oncology, Comprehensive Cancer Center of Wake Forest University, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA
Resource Type: Journal article
Publication Details: Redox biology, Vol.1(1), pp.70-79
DOI: 10.1016/j.redox.2012.12.006
PMID: 24024139
PMCID: PMC3757675
NLM abbreviation: Redox Biol
ISSN: 2213-2317
eISSN: 2213-2317
Publisher: Elsevier
Grant note: DOI: 10.13039/100000002, name: National Institutes of Health, award: CA82722 (to M.E. Robbins), CA73612, CA66081 (to F.E. Domann), NS24621 (to S.A. Moore)
Language: English
Date published: 2013
Academic Unit: Pathology; Surgery; Radiation Oncology
Record Identifier: 9984047612502771

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