Nox4 mediates the expression of plasminogen activator inhibitor-1 via p38 MAPK pathway in cultured human endothelial cells

Jaulmes, Amandine; Sansilvestri-Morel, Patricia; Rolland-Valognes, Gaëlle; Bernhardt, Fabienne; Gaertner, Roger; Lockhart, Brian P.; Cordi, Alex; Wierzbicki, Michel; Rupin, Alain; Verbeuren, Tony J.

doi:10.1016/j.thromres.2009.05.018

Cited by 50 publications

(31 citation statements)

References 36 publications

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“…to underphosphorylated p38 in ES cells [25] and also in endothelial cells [44,45], and we found that both p38 phosphorylation and NOX4 transcription are downregulated during low glucose differentiation. Interestingly, Nox4 has been recently reported to reside in the mitochondrion of the kidney cortex, and its expression is sensitive to glucose levels [46].…”

Section: Discussionsupporting

confidence: 52%

Mitochondrial Reactive Oxygen Species Mediate Cardiomyocyte Formation from Embryonic Stem Cells in High Glucose

et al. 2010

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Accumulating evidence points to reactive oxygen species (ROS) as important signaling molecules for cardiomyocyte differentiation in embryonic stem (ES) cells. Given that ES cells are normally maintained and differentiated in medium containing supraphysiological levels of glucose (25 mM), a condition which is known to result in enhanced cellular ROS formation, we questioned whether this high glucose concentration was necessary for cardiomyocyte lineage potential. We show here that ES cells cultured in physiological glucose (5 mM), maintained their general stemness qualities but displayed an altered mitochondrial metabolism, which resulted in decreased ROS production. Furthermore, ES and induced pluripotent stem (iPS) cells differentiated in lower glucose concentrations failed to generate cardiomyocyte structures; an effect mimicked with antioxidant treatments using catalase, N-acetyl cysteine and mitoubiquinone, under high glucose conditions in ES cells. Molecular analysis revealed that ES cells differentiated in 5 mM glucose had reduced expression of the pro-cardiac NOX4 gene and diminished phosphorylation of p38 mitogen-activated protein kinase (MAPK), together with specific changes in the cardiac transcriptional network. These outcomes could be reversed by supplementation of low glucose cultures with ascorbic acid, paradoxically acting as a pro-oxidant. Furthermore, forced expression of an upstream p38 MAPK kinase (MKK6) could bypass the requirement for ROS during differentiation to cardiomyocytes under low glucose conditions, illustrating a key role for p38 in the cardiac differentiation program. Together these data demonstrate that endogenous ROS control is important for cardiomyocyte formation from ES cells, and furthermore that supraphysiological glucose, by supplying ROS, is absolutely required.

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Section: Discussionsupporting

confidence: 52%

Mitochondrial Reactive Oxygen Species Mediate Cardiomyocyte Formation from Embryonic Stem Cells in High Glucose

et al. 2010

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“…Given the strong impact of Nox enzymes on the signal transduction by MAP kinases and inflammatory signaling, it is expected that their transcription factors activator protein-1 (AP-1) [113][114][115] and nuclear factor kappa B (NFκB) [49,17] are indirectly Nox dependent. This is probably also true for other stress-responsive factors like Erg-1 [116].…”

Section: Transcription Factorsmentioning

confidence: 99%

Redox-mediated signal transduction by cardiovascular Nox NADPH oxidases

Brandes

Weißmann

Schröder

2014

Journal of Molecular and Cellular Cardiology

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“…Evidence exists that proinflammatory genes are regulated by transcription factors whose expression, structure, subcellular localization, or affinity for DNA is directly or indirectly regulated by the level of oxidative stress. In addition to transcription factors, the function of several protein kinase/phosphatases, phospholipases, and ion channels is affected by cellular redox conditions (Jaulmes et al 2009;Maloney et al 2009). …”

Section: Introductionmentioning

confidence: 99%

NADPH oxidase-derived reactive oxygen species: involvement in vascular physiology and pathology

Manea¹

2010

Cell Tissue Res

148

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Reactive oxygen species (ROS) are essential mediators of normal cell physiology. However, in the last few decades, it has become evident that ROS overproduction and/or alterations of the antioxidant system associated with inflammation and metabolic dysfunction are key pathological triggers of cardiovascular disorders. NADPH oxidases (Nox) represent a class of hetero-oligomeric enzymes whose primary function is the generation of ROS. In the vasculature, Nox-derived ROS contribute to the maintenance of vascular tone and regulate important processes such as cell growth, proliferation, differentiation, apoptosis, cytoskeletal organization, and cell migration. Under pathological conditions, excessive Nox-dependent ROS formation, which is generally associated with the up-regulation of different Nox subtypes, induces dysregulation of the redox control systems and promotes oxidative injury of the cardiovascular cells. The molecular mechanism of Nox-derived ROS generation and the means by which this class of molecule contributes to vascular damage remain debatable issues. This review focuses on the processes of ROS formation, molecular targets, and neutralization in the vasculature and provides an overview of the novel concepts regarding Nox functions, expression, and regulation in vascular health and disease. Because Nox enzymes are the most important sources of ROS in the vasculature, therapeutic perspectives to counteract Nox-dependent oxidative stress in the cardiovascular system are discussed.

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Nox4 mediates the expression of plasminogen activator inhibitor-1 via p38 MAPK pathway in cultured human endothelial cells

Cited by 50 publications

References 36 publications

Mitochondrial Reactive Oxygen Species Mediate Cardiomyocyte Formation from Embryonic Stem Cells in High Glucose

Mitochondrial Reactive Oxygen Species Mediate Cardiomyocyte Formation from Embryonic Stem Cells in High Glucose

Redox-mediated signal transduction by cardiovascular Nox NADPH oxidases

NADPH oxidase-derived reactive oxygen species: involvement in vascular physiology and pathology

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