Cadmium and mercury cause an oxidative stress-induced
endothelial dysfunction |
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Authors: | Matthew B Wolf John W Baynes |
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Institution: | (1) Department of Pharmacology, Physiology & Neuroscience, University of South Carolina School of Medicine, Columbia, SC 29208, USA;(2) Developmental Biology and Anatomy, University of South Carolina School of Medicine, Columbia, SC 29208, USA |
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Abstract: | We investigated the ability of cadmium and mercury ions to cause endothelial dysfunction in bovine pulmonary artery endothelial
cell monolayers. Exposure of monolayers for 48 h to metal concentrations greater than 3–5 μM produced profound cytotoxicity
(increased lactate dehydrogenase leakage), a permeability barrier failure, depletion of glutathione and ATP and almost complete
inhibition of the activity of key thiol enzymes, glucose-6-phosphate dehydrogenase (G6PDH) and glyceraldehyde-3-phosphate
dehydrogenase (GAPDH). In contrast, metal concentrations less than 1–2 μM induced increases in glutathione and thiol-enzyme
activities with minimal changes in LDH leakage, barrier function and ATP content. At shorter incubation times (24 h or less),
high concentrations of cadmium caused glutathione induction rather than depletion. Thus, oxidative stress and cytotoxicity
induced by lower concentrations of the metal ions stimulate compensatory responses, including increased synthesis of glutathione,
which presumably preserved the activity of key thiol enzymes, however these responses were not sustainable at higher metal
ion concentrations. We conclude, while high concentrations of heavy metals are cytotoxic, lower concentration induce a compensatory
protective response, which may explain threshold effects in metal-ion toxicity. |
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Keywords: | heavy metals oxidative stress endothelial dysfunction endothelial barrier dysfunction glutathione ATP thiol enzymes |
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