Biochemical and Biophysical Research Communications
Rosuvastatin upregulates the antioxidant defense protein heme oxygenase-1ā
Section snippets
Materials and methods
Materials. Fetal bovine serum, cell culture media, and penicillināstreptomycin were obtained from Gibco (Eggenstein, FRG). The Chemiluminescence Western Blotting Kit was from Amersham (Freiburg, FRG) and the Random Primed DNA Labeling Kit was from Roche (Penzberg, FRG). HO-1 primary antibody and anti-rabbit peroxidase-conjugated secondary antibody were obtained from Alexis (GrĆ¼nberg, FRG). Rosuvastatin was provided by AstraZeneca UK. For HO-1 probes, the template was an EcoRI restriction
HO-1 mRNA and protein analysis
An 8-h incubation with rosuvastatin led to a concentration-dependent increase of HO-1 mRNA expression by up to twofold over basal values (Fig. 1). Rosuvastatin-dependent HO-1 induction was also observed at the protein level (Fig. 2). Concentration-dependent increases in HO-1 protein occurred between 3 and 300Ā Ī¼M rosuvastatin (Fig. 2). Induction of HO-1 protein was detectable after 4Ā h of exposure and reached a maximum after 12Ā h (not shown). The HMG-CoA product mevalonate was used to investigate
Discussion
It is generally accepted that mechanisms beyond reduction of plasma cholesterol contribute significantly to the antiatherogenic and tissue protective properties of statins. Pleiotropic, cholesterol-independent effects of statins previously reported include elevations in eNOS and tissue-type plasminogen activator expression as well as reduction of pro-inflammatory signaling such as cytokine and oxygen radical formation [7], [8].
This study demonstrates that the antioxidant defense protein heme
References (41)
- et al.
The evolving role of statins in the management of atherosclerosis
J. Am. Coll. Cardiol.
(2000) - et al.
Inhibition of the mevalonate pathway: benefits beyond cholesterol reduction?
Lancet
(1996) - et al.
The lipid and non-lipid effects of statins
Pharmacol. Ther.
(2003) - et al.
Rosuvastatin, a new HMG-CoA reductase inhibitor, upregulates endothelial nitric oxide synthase and protects from ischemic stroke in mice
Brain Res.
(2002) - et al.
Heme oxygenase-1 induction may explain the antioxidant profile of aspirin
Biochem. Biophys. Res. Commun.
(2003) - et al.
Gene regulation of heme oxygenase-1 as a therapeutic target
Biochem. Pharmacol.
(2000) - et al.
Atrial natriuretic peptide reduces cyclosporin toxicity in renal cells: role of cGMP and heme oxygenase-1
Free Radic. Biol. Med.
(2002) - et al.
Validation of lucigenin (bis-N-methylacridinium) as a chemilumigenic probe for detecting superoxide anion radical production by enzymatic and cellular systems
J. Biol. Chem.
(1998) - et al.
Inhibition of protein geranylgeranylation causes a superinduction of nitric-oxide synthase-2 by interleukin-1beta in vascular smooth muscle cells
J. Biol. Chem.
(1997) - et al.
Post-transcriptional regulation of endothelial nitric oxide synthase mRNA stability by Rho GTPase
J. Biol. Chem.
(1998)
Current perspectives on statins
Circulation
Anti-atherosclerotic effects of statins: lessons from prevention trials
J. Cardiovasc. Risk.
Statins and risk of coronary heart disease
JAMA
Serum cholesterol in young men and subsequent cardiovascular disease
N. Engl. J. Med.
Microsatellite polymorphism in promoter of heme oxygenase-1 gene is associated with susceptibility to coronary artery disease in type 2 diabetic patients
Hum. Genet.
Carbon monoxide suppresses arteriosclerotic lesions associated with chronic graft rejection and with balloon injury
Nat. Med.
Absence of heme oxygenase-1 exacerbates atherosclerotic lesion formation and vascular remodeling
FASEB J.
Biliverdin reductase: a major physiologic cytoprotectant
Proc. Natl. Acad. Sci. USA
Heme oxygenase: colors of defense against cellular stress
Am. J. Physiol. Lung Cell. Mol. Physiol.
Heme oxygenase-1 is a cGMP-inducible endothelial protein and mediates the cytoprotective action of nitric oxide
Arterioscler. Thromb. Vasc. Biol.
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Abbreviations: HO-1, heme oxygenase-1; HMG-CoA, 3-hydroxy-3-methylglutaryl coenzyme A; NO, nitric oxide; NOS, NO synthase; l-NAME, N-nitro-l-arginine-methylester; ROS, reactive oxygen species; SnPP, tin protoporphyrin-IX.