- Keywords
- adherence,
- MeSH
- Hypoxia MeSH
- Integrins physiology MeSH
- Humans MeSH
- Luminescent Measurements utilization MeSH
- Macrophages * physiology MeSH
- NADPH Oxidases secretion MeSH
- Reactive Oxygen Species MeSH
- Oxygen Compounds metabolism MeSH
- Check Tag
- Humans MeSH
- Publication type
- Research Support, Non-U.S. Gov't MeSH
This short review article summarizes what is known clinically and biochemically about the seven human NADPH oxidases. Emphasis is put on the connection between mutations in the catalytic and regulatory subunits of Nox2, the phagocyte defense enzyme, with syndromes like chronic granulomatous disease, as well as a number of chronic inflammatory diseases. These arise paradoxically from a lack of reactive oxygen species production needed as second messengers for immune regulation. Both Nox2 and the six other human NADPH oxidases display signaling functions in addition to the functions of these enzymes in specialized biochemical reactions, for instance, synthesis of the hormone thyroxine. NADPH oxidases are also needed by Saccharomyces cerevisiae cells for the regulation of the actin cytoskeleton in times of stress or developmental changes, such as pseudohyphae formation. The article shows that in certain cancer cells Nox4 is also involved in the re-structuring of the actin cytoskeleton, which is required for cell mobility and therefore for metastasis.
- MeSH
- Eukaryotic Cells * MeSH
- Humans MeSH
- NADPH Oxidase 2 MeSH
- NADPH Oxidase 4 MeSH
- NADPH Oxidases * physiology MeSH
- Reactive Oxygen Species MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
- MeSH
- Autonomic Fibers, Preganglionic MeSH
- Rabbits MeSH
- Neurons metabolism MeSH
- Nitric Oxide MeSH
- Animals MeSH
- Check Tag
- Rabbits MeSH
- Animals MeSH
- MeSH
- Nerve Tissue metabolism MeSH
- Nitric Oxide metabolism MeSH
- Spleen metabolism MeSH
- Animals MeSH
- Check Tag
- Animals MeSH
- MeSH
- Mice MeSH
- Nitrogen Oxides metabolism MeSH
- Thymus Gland metabolism MeSH
- Animals MeSH
- Check Tag
- Mice MeSH
- Animals MeSH
Cardiovascular side effects are frequent problems accompanying systemic glucocorticoid therapy, although the underlying mechanisms are not fully resolved. Reactive oxygen species (ROS) have been shown to promote various cardiovascular diseases although the link between glucocorticoid and ROS signaling has been controversial. As the family of NADPH oxidases has been identified as important source of ROS in the cardiovascular system we investigated the role of NADPH oxidases in response to the synthetic glucocorticoid dexamethasone in the cardiovascular system in vitro and in vivo in mice lacking functional NADPH oxidases due to a mutation in the gene coding for the essential NADPH oxidase subunit p22phox. We show that dexamethasone induced NADPH oxidase-dependent ROS generation, leading to vascular proliferation and angiogenesis due to activation of the transcription factor hypoxia-inducible factor-1 (HIF1). Chronic treatment of mice with low doses of dexamethasone resulted in the development of systemic hypertension, cardiac hypertrophy and left ventricular dysfunction, as well as in pulmonary hypertension and pulmonary vascular remodeling. In contrast, mice deficient in p22phox-dependent NADPH oxidases were protected against these cardiovascular side effects. Mechanistically, dexamethasone failed to upregulate HIF1α levels in these mice, while vascular HIF1α deficiency prevented pulmonary vascular remodeling. Thus, p22phox-dependent NADPH oxidases and activation of the HIF pathway are critical elements in dexamethasone-induced cardiovascular pathologies and might provide interesting targets to limit cardiovascular side effects in patients on chronic glucocorticoid therapy.
- MeSH
- Hypoxia-Inducible Factor 1 MeSH
- Glucocorticoids MeSH
- Humans MeSH
- Mice MeSH
- NADPH Oxidases genetics MeSH
- Heart Diseases * MeSH
- Hypertension, Pulmonary * chemically induced MeSH
- Reactive Oxygen Species MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
Oxidative stress closely related to the progression and severity of myocardial infarction (MI). Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 4 (NOX4) is one of the major enzymes that generate reactive oxygen species (ROS) in cardiovascular system. Here, we aim to elucidate the pathological role of NOX4 in MI. MI mouse model was created by the coronary artery ligation. NOX4 was specifically knocked down in heart through intramyocardial injection of siRNA. NOX4 expression and oxidative stress indicators were determined at different time points using qRT-PCR, Western blot, and ELISA, and then analyzed by Pearson's correlation. Cardiac function was evaluated by using echocardiographic technique. NOX4 was upregulated in myocardial tissues of MI mice, which positively correlated with the elevation of oxidative stress indicators. Knockdown of NOX4 in heart significantly reduced the production of ROS and the level of oxidative stress in left ventricle tissues, which was accompanied by significant improvement of cardiac function in MI mice. Selective knockdown of NOX4 in heart attenuates MI-induced oxidative stress and improves cardiac function, suggesting inhibition of NOX4/ROS axis in heart using siRNA is a potential therapeutic treatment for MI-induced cardiac dysfunction.
- MeSH
- Myocardial Infarction * genetics MeSH
- Coronary Vessels MeSH
- Disease Models, Animal MeSH
- Mice MeSH
- NADPH Oxidase 4 * genetics MeSH
- Oxidative Stress * MeSH
- Reactive Oxygen Species MeSH
- Animals MeSH
- Check Tag
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
