Tanshinone IIA reduces macrophage death induced by hydrogen peroxide by upregulating glutathione peroxidase
Autor: | Gary W. Elmer, Yu I. Li, Renee C. LeBoeuf |
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Rok vydání: | 2008 |
Předmět: |
Programmed cell death
DNA Fragmentation Pharmacology Protective Agents medicine.disease_cause Salvia miltiorrhiza Article General Biochemistry Genetics and Molecular Biology Membrane Potentials Mice chemistry.chemical_compound medicine Animals Chromans General Pharmacology Toxicology and Pharmaceutics Cells Cultured Caspase chemistry.chemical_classification Glutathione Peroxidase Cell Death biology Reverse Transcriptase Polymerase Chain Reaction Chemistry Macrophages Glutathione peroxidase Hydrogen Peroxide General Medicine Phenanthrenes Catalase Oxidants Up-Regulation Oxidative Stress Biochemistry Apoptosis Caspases Abietanes Mitochondrial Membranes biology.protein Trolox Oxidative stress |
Zdroj: | Life Sciences. 83:557-562 |
ISSN: | 0024-3205 |
Popis: | Aims Tanshinone IIA is an important ingredient in the herb danshen ( Salvia miltiorrhiza ), which has been used to treat cardiovascular diseases such as atherosclerosis and angina for hundreds of years in China. There are numerous reports that TIIA has anti-oxidant properties but the chemical structure indicates that TIIA is fully oxidized. Here, we test the hypothesis that TIIA alters the expression and/or activity of specific anti-oxidation enzymes to protect cells from oxidant damage. Main methods We utilized J774 macrophages to model cellular responses to TIIA when challenged with H 2 O 2 . Expression and activity levels of several anti-oxidation enzymes were investigated and the only system modulated by TIIA was glutathione peroxidase (GPx). Key findings GPx-1 mRNA levels were significantly increased by TIIA but not the vitamin E analogue, Trolox. GPx activities were also significantly increased by TIIA. Mercaptosuccinic acid inhibited GPx activity and the protective effect of TIIA was attenuated. Thus, TIIA protects cultured macrophages from H 2 O 2 -induced cell death and protection is mediated in large part by TIIA induction of GPx gene expression and activity. Significance Because of the importance of GPx in health and because TIIA is able to modulate GPx activity to some extent in cell culture, we suggest that TIIA is a worthwhile candidate for further study in animal models of atherosclerosis and eventually in human prospective trials. |
Databáze: | OpenAIRE |
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