Ceramide-induced impairment of endothelial function is prevented by CuZn superoxide dismutase overexpression

Sean P Didion; Frank M Faraci

doi:10.1161/01.ATV.0000149868.74075.5d

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Ceramide-induced impairment of endothelial function is prevented by CuZn superoxide dismutase overexpression

Journal article

Open access

Peer reviewed

Ceramide-induced impairment of endothelial function is prevented by CuZn superoxide dismutase overexpression

Sean P Didion and Frank M Faraci

Arteriosclerosis, thrombosis, and vascular biology, Vol.25(1), pp.90-95

01/2005

DOI: 10.1161/01.ATV.0000149868.74075.5d

PMID: 15528474

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Abstract

Ceramide is an important intracellular second messenger that may also increase superoxide. The goal of this study was to determine whether overexpression of CuZn superoxide dismutase (SOD) protects against ceramide-induced increases in vascular superoxide and endothelial dysfunction. Carotid arteries from CuZnSOD-transgenic (CuZnSOD-Tg) and nontransgenic littermates were examined in vitro. Immunohistochemistry confirmed that CuZnSOD protein was greater in carotid artery from CuZnSOD-Tg compared with nontransgenic mice. Ceramide (N-acetyl-d-sphingosine; 1 and 10 micromol/L) produced concentration-dependent impairment (P<0.05) of vasorelaxation in response to the endothelium-dependent agonist acetylcholine (ACh) in nontransgenic mice. For example, 100 micromol/L ACh relaxed arteries from nontransgenic mice by 96+/-4% and 52+/-5% in the presence of vehicle and 10 micromol/L ceramide, respectively. In contrast, ceramide (1 or 10 micromol/L) had no effect (P>0.05) on responses of carotid artery to ACh in CuZnSOD-Tg mice. Ceramide had no effect on nitroprusside- or papaverine-induced relaxation in CuZnSOD-Tg or nontransgenic mice. Ceramide increased superoxide in arteries from nontransgenic vessels, and this effect was prevented by polyethyleneglycol-SOD (50 U/mL) or overexpression of CuZnSOD. These results suggest that ceramide-induced increases in superoxide impair endothelium-dependent relaxation, and that select overexpression of the CuZn isoform of SOD prevents ceramide-induced oxidative stress in vessels.

Superoxide Dismutase - biosynthesis

Mice, Inbred C57BL

Carotid Arteries - chemistry

Male

Endothelium, Vascular - physiology

Immunohistochemistry - methods

Animals

Carotid Arteries - enzymology

Female

Mice

Endothelium - enzymology

Ceramides - physiology

Endothelium - physiology

Details

Title: Subtitle: Ceramide-induced impairment of endothelial function is prevented by CuZn superoxide dismutase overexpression
Creators: Sean P Didion - Department of Internal Medicine, 2000 Medical Laboratories, Cardiovascular Center, The University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA. sean-didion@uiowa.edu
Frank M Faraci
Resource Type: Journal article
Publication Details: Arteriosclerosis, thrombosis, and vascular biology, Vol.25(1), pp.90-95
DOI: 10.1161/01.ATV.0000149868.74075.5d
PMID: 15528474
NLM abbreviation: Arterioscler Thromb Vasc Biol
ISSN: 1079-5642
eISSN: 1524-4636
Publisher: United States
Grant note: HL-38901 / NHLBI NIH HHS NS-24621 / NINDS NIH HHS DK-25295 / NIDDK NIH HHS HL-62984 / NHLBI NIH HHS
Language: English
Date published: 01/2005
Academic Unit: Cardiovascular Medicine; Neuroscience and Pharmacology; Internal Medicine
Record Identifier: 9984040480002771

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