Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:1.6.3.1 (
NADPH oxidase
)
11,281
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Cardiomyogenesis in differentiating mouse embryonic stem (ES) cells is promoted by
cardiotrophin-1
(
CT-1
), a member of the IL-6 interleukin superfamily that acts through the tall gp130 cytokine receptor. We show that prooxidants (menadione, hydrogen peroxide) as well as chemical (CoCl2) and physiological (1% O2) hypoxia increased
CT-1
as well as HIF-1alpha protein and mRNA expression in embryoid bodies, indicating that
CT-1
expression is regulated by reactive oxygen species (ROS) and hypoxia. Treatment with either prooxidants or chemical hypoxia increased gp130 phosphorylation and protein expression of
NADPH oxidase
subunits p22-phox, p47-phox, p67-phox, as well as Nox1 and Nox4 mRNA. Consequently, inhibition of
NADPH oxidase
activity by diphenylen iodonium chloride (DPI) and apocynin abolished prooxidant- and chemical hypoxia-induced upregulation of
CT-1
. Prooxidants and chemical hypoxia activated ERK1,2, JNK and p38 as well as PI3-kinase. The proxidant- and CoCl2-mediated upregulation of
CT-1
was significantly inhibited in the presence of the ERK1,2 antagonist UO126, the JNK antagonist SP600125, the p38 antagonist SKF86002, the PI3-kinase antagonist LY294002, the Jak-2 antagonist AG490 as well as in the presence of free radical scavengers. Moreover, developing embryoid bodies derived from HIF-1alpha-/- ES cells lack cardiomyogenesis, and prooxidants as well as chemical hypoxia failed to upregulate
CT-1
expression. Our results demonstrate that
CT-1
expression in ES cells is regulated by ROS and HIF-1alpha and imply a crucial role of
CT-1
in the survival and proliferation of ES-cell-derived cardiac cells.
...
PMID:Regulation of cardiotrophin-1 expression in mouse embryonic stem cells by HIF-1alpha and intracellular reactive oxygen species. 1650 96
Left ventricular hypertrophy (LVH) is an independent marker of mortality in hypertension. Although the mechanisms contributing to LVH are complex, inflammation and oxidative stress may favor its development. We analyzed the association of the phagocytic
NADPH oxidase
-mediated superoxide anion release and LVH in patients with essential hypertension and the role of
cardiotrophin-1
(
CT-1
) and interleukin-6 (IL-6), cytokines implicated in cardiac growth. Blood pressure, echocardiography data, and serum
CT-1
and IL-6 levels were obtained in 140 subjects: 18 normotensives without LVH, 42 hypertensives without LVH, and 80 hypertensives with LVH. The
NADPH oxidase
-dependent superoxide production was assessed by chemiluminescence in peripheral blood mononuclear cells. Peripheral blood mononuclear cells were stimulated with
CT-1
in vitro. Superoxide anion production by peripheral blood mononuclear cells associated with LVH and correlated with the left ventricular mass index. Serum
CT-1
and IL-6 levels, which associated with the left ventricular mass index, correlated with superoxide production. Serum
CT-1
and IL-6 levels were correlated.
CT-1
stimulated
NADPH oxidase
superoxide production in peripheral blood mononuclear cells, which resulted in an increased release of IL-6. Our results show that superoxide anion production by the phagocytic
NADPH oxidase
associates with hypertensive heart disease, being significantly enhanced in hypertensive patients with LVH. This may be attributable to the activation of the
NADPH oxidase
by
CT-1
and the subsequent release of IL-6. The phagocytic
NADPH oxidase
may be a therapeutic target in hypertensive heart disease.
...
PMID:Association of phagocytic NADPH oxidase activity with hypertensive heart disease: a role for cardiotrophin-1? 2432 51
