It has been suggested that oxidative stress may play an important role in the pathogenesis of diabetic complications. Hyperglycemia may cause increased production of free radicals, and evidence supports a prominent role for these reactive molecules as mediators of endothelial cell dysfunction in diabetes. It has been demonstrated that active oxygen species induce antioxidant enzyme expression in some tissues, and this phenomenon is considered proof of an existing oxygen-dependent toxicity. In this study, human endothelial cells from umbilical vein, immortalized human endothelial cells, and immortalized human endothelial cells transfected to express high glutathione peroxidase levels were grown in normal and high-glucose conditions. High glucose delayed replication after 7 and 14 days of culture of human endothelial cells, both from umbilical vein and immortalized, while transfected cells were not affected. The activity and the mRNA expression of the antioxidant enzymes CuZn-superoxide-dismutase, Mn-superoxide-dismutase, catalase, and glutathione peroxidase were evaluated after 2, 7, and 14 days of culture. High glucose at days 7 and 14 induced an overexpression of CuZn-superoxide-dismutase, catalase, and glutathione peroxidase in both human endothelial cells from umbilical vein and immortalized human endothelial cells, while in transfected cells it did not. This study demonstrates that high glucose induces an increase in antioxidant enzyme levels in human endothelial cells, suggesting that elevated glucose levels may produce an oxidative stress in the cells.
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Original Articles|
April 01 1996
High Glucose Induces Antioxidant Enzymes in Human Endothelial Cells in Culture: Evidence Linking Hyperglycemia and Oxidative Stress
Antonio Ceriello;
Antonio Ceriello
Department of Clinical and Experimental Pathology and Medicine, University of Udine
Udine, Italy
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Patrizia dello Russo;
Patrizia dello Russo
Istituto Immunotrafusionale, General Hospital
Udine, Italy
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Paul Amstad;
Paul Amstad
Department of Carcinogenesis, Swiss Institute for Experimental Cancer Research
Epalinges, Lausanne, Switzerland
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Peter Cerutti
Peter Cerutti
Department of Carcinogenesis, Swiss Institute for Experimental Cancer Research
Epalinges, Lausanne, Switzerland
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Address correspondence and reprint requests to Dr. Antonio Ceriello, Dept. of Clinical and Experimental Pathology and Medicine, Chair of Internal Medicine, University of Udine, P. le S. Maria della Misericordia, 33100 Udine, Italy.
Diabetes 1996;45(4):471–477
Article history
Received:
December 22 1994
Revision Received:
November 16 1995
Accepted:
November 16 1995
PubMed:
8603769
Citation
Antonio Ceriello, Patrizia dello Russo, Paul Amstad, Peter Cerutti; High Glucose Induces Antioxidant Enzymes in Human Endothelial Cells in Culture: Evidence Linking Hyperglycemia and Oxidative Stress. Diabetes 1 April 1996; 45 (4): 471–477. https://doi.org/10.2337/diab.45.4.471
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