Depressed glutathione synthesis precedes oxidative stress and atherogenesis in Apo-E−/− mice
| Autor: | David E. Newby, Saibal K. Biswas, Ian L. Megson, Irfan Rahman |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
GPX1
medicine.medical_specialty Time Factors Antioxidant GPX3 Glutamate-Cysteine Ligase medicine.medical_treatment Glutathione reductase Biophysics Biology GPX4 medicine.disease_cause Biochemistry Mice chemistry.chemical_compound Apolipoproteins E Internal medicine medicine Animals Molecular Biology Mice Knockout chemistry.chemical_classification Glutathione Peroxidase Glutathione peroxidase Cell Biology Glutathione Atherosclerosis Oxidative Stress Endocrinology chemistry Models Animal Lipid Peroxidation Oxidative stress |
| Zdroj: | Biochemical and Biophysical Research Communications. 338:1368-1373 |
| ISSN: | 0006-291X |
| DOI: | 10.1016/j.bbrc.2005.10.098 |
| Popis: | Glutathione is a vital intracellular antioxidant. The enzymes involved in its synthesis and utilisation are tightly regulated, but the importance of glutathione regulation in atherogenesis is poorly understood. Here, we establish that glutathione is severely (approximately 80%) depleted very early (10 weeks) in the atheroma-prone aortic arch of male apoprotein E-deficient (Apo-E(-/-)) mice compared to age-matched wild-type controls. Importantly, this event pre-empts lipid peroxidation and detectable atheroma by several months. Depletion of glutathione was associated with excessive oxidant burden and reduced transcription and activity of the rate-limiting enzyme for glutathione synthesis, gamma-glutamylcysteine ligase, together with the glutathione-dependent antioxidant enzyme, glutathione peroxidase. Depletion via reduced synthesis of glutathione precedes lipid peroxidation and atherogenesis in Apo-E(-/-) mice. We suggest that glutathione deficiency is central to the failure of the intracellular antioxidant defences and is causally implicated in the pathogenesis of atherosclerosis. Modification of the glutathione pathway may present a novel and important therapeutic target in the prevention and treatment of atherosclerosis. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect