Humanin is expressed in human vascular walls and has a cytoprotective effect against oxidized LDL-induced oxidative stress
Autor: | Yun K. Oh, Amir Lerman, Richard E. Pagano, Andreas S. Schroeder, Laura J. Cobb, Pinchas Cohen, Lilach O. Lerman, Adi R. Bachar, Lea Scheffer, Hiromi Nakamura |
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Rok vydání: | 2010 |
Předmět: |
Adult
Ceramide Programmed cell death Physiology Apoptosis Coronary Artery Disease Ceramides medicine.disease_cause chemistry.chemical_compound Physiology (medical) In Situ Nick-End Labeling Humans Medicine Saphenous Vein RNA Messenger Mammary Arteries Cells Cultured Aged Humanin chemistry.chemical_classification Reactive oxygen species business.industry Intracellular Signaling Peptides and Proteins Endothelial Cells Original Articles Anatomy Middle Aged Coronary Vessels Immunohistochemistry Molecular biology Lipoproteins LDL Endothelial stem cell Oxidative Stress chemistry Cytoprotection Reactive Oxygen Species Cardiology and Cardiovascular Medicine business Neuron death Oxidative stress |
Zdroj: | Cardiovascular Research. 88:360-366 |
ISSN: | 0008-6363 |
DOI: | 10.1093/cvr/cvq191 |
Popis: | Humanin (HN) is a 24-amino acid peptide that has been shown to have an anti-apoptotic function against neuronal cell death caused by Alzheimer's disease. Increased oxidative stress, one of the major factors contributing to this cell death, also plays an important role in the inflammatory process of atherosclerosis. The current study was designed to test the hypothesis that HN is expressed in the human vascular wall and may protect against oxidative stress. Methods HN expression in the vascular wall was detected by immunostaining in the endothelial cell layer of human internal mammary arteries (n ¼ 5), atherosclerotic coronary arteries (n ¼ 17), and sections of the greater saphenous vein (n ¼ 3). HN mRNA was expressed in the human aortic endothelial cells (HAECs). Cytoprotective effects of HN against oxidative stress were tested in vitro in HAECs. Pre-treatment with 0.1 mM HN reduced oxidized LDL (Ox-LDL)-induced (i) formation of reactive oxygen species by 50%, (ii) apoptosis by � 50% as determined by TUNEL staining, and (iii) formation of ceramide, a lipid second messenger involved in the apoptosis signalling cascade, by � 20%. Conclusion The current study demonstrates for the first time the expression of HN in the endothelial cell layer of human blood vessels. Exogenous addition of HN to endothelial cell cultures was shown to be effective against Ox-LDL-induced apoptosis. These findings suggest that HN may play a role and may have a protective effect in early atherosclerosis in humans. |
Databáze: | OpenAIRE |
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