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Rapid Quantification of Oxidized and Reduced Forms of Glutathione Using Ortho -phthalaldehyde in Cultured Mammalian Cells In Vitro
Published on: June 28, 2024
Homocysteine and glutathione peroxidase-1
Edith Lubos1, Joseph Loscalzo, Diane E Handy
1Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
Insights
Mildly elevated homocysteine (Hcy) increases cardiovascular disease risk by reducing nitric oxide (NO) availability. Glutathione peroxidase-1 (GPx-1) plays a key role in mitigating these harmful effects.
Area of Science:
- Biochemistry
- Cardiovascular Science
- Molecular Biology
Background:
- Mildly elevated homocysteine (Hcy) is linked to atherothrombotic vascular disease.
- Hcy reduces nitric oxide (NO) bioavailability, increasing vascular oxidant stress.
- Glutathione peroxidase-1 (GPx-1) is a key antioxidant enzyme potentially affected by Hcy.
Purpose of the Study:
- To review the molecular mechanisms of Hcy-induced endothelial dysfunction.
- To explore the role of GPx-1 in hyperhomocysteinemia and cardiovascular disease (CVD).
- To summarize current knowledge on Hcy metabolism and its effects.
Main Methods:
- Review of in vitro and in vivo experimental studies.
- Analysis of clinical studies on plasma total homocysteine (tHcy) and GPx-1.
- Synthesis of data on Hcy metabolism and endothelial function.
Main Results:
- Hcy increases vascular oxidant stress and inhibits antioxidant capacity.
- Hcy may decrease GPx-1 expression, contributing to endothelial dysfunction.
- GPx-1 overexpression may offer a compensatory protective effect.
Conclusions:
- Hcy-induced endothelial dysfunction involves complex interactions with GPx-1.
- Understanding the Hcy-GPx-1 relationship is crucial for CVD pathogenesis.
- Targeting GPx-1 may offer therapeutic strategies for Hcy-related vascular issues.
Abstract:
Mildly elevated homocysteine levels (Hcy) increase the risk for atherothrombotic vascular disease in the coronary, cerebrovascular, and peripheral arterial circulations. The molecular mechanisms responsible for decreased bioavailability of endothelium-derived nitric oxide (NO) by Hcy involve an increase of vascular oxidant stress and inhibition of important antioxidant capacity. Glutathione peroxidase-1 (GPx-1), a selenocysteine-containing antioxidant enzyme, may be a key target of Hcy's deleterious actions, and several experimental and clinical studies have demonstrated a complex relationship between plasma total homocysteine (tHcy), GPx-1, and endothelial dysfunction. Hcy may promote endothelial dysfunction, in part by decreasing GPx-1 expression; however, there is evidence to suggest that overexpression of GPx-1 can compensate for these effects. This review summarizes the current knowledge of the metabolism of Hcy, the effects of hyperhomocysteinemia observed in in vitro and in vivo models that lead to endothelial dysfunction and the possible mechanisms for these actions, and the role of GPx-1 in the pathogenesis of Hcy-induced cardiovascular disease (CVD).
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