Kyushu University · Medicine
Professor Tetsuro Ago's research lab specializes in redox biology and cardiovascular pathology, focusing on the role of NAD(P)H oxidase-derived reactive oxygen species (ROS) in cardiac and vascular diseases. The lab investigates the molecular mechanisms of Nox family isoforms—particularly Nox1, Nox2, and Nox4—in mediating oxidative stress, cellular dysfunction, and organ remodeling in conditions such as cardiac hypertrophy, heart failure, and vascular aging. A central theme is the regulation of Nox oxidases by post-translational modifications, subcellular localization, and protein-protein interactions involving cytosolic regulators like p47phox and lipid signaling molecules. The lab also explores the crosstalk between ROS signaling and mitochondrial dysfunction in disease progression.
Figures are computed from collected data and may differ slightly.
Upregulation of Nox4 by hypertrophic stimuli and aging induces oxidative stress, apoptosis and LV dysfunction, in part because of mitochondrial insufficiency caused by increased O(2)(-) production and consequent cysteine oxidation in mitochondrial proteins.
Background— Recent evidence has suggested that reactive oxygen species are important signaling molecules in vascular cells and play a pivotal role in the development of vascular diseases. The activity of NAD(P)H oxidase has been identified as the major source of reactive oxygen species in vascular endothelial cells. However, the precise molecular structure and the mechanism of activation of the oxidase have remained poorly understood. Methods and Results— Here, we investigated the molecular iden
Activation of the superoxide-producing phagocyte NADPH oxidase requires interaction between p47(phox) and p22(phox), which is mediated via the SH3 domains of the former protein. This interaction is considered to be induced by exposure of the domains that are normally masked by an intramolecular interaction with the C-terminal region of p47(phox). Here we locate the intramolecular SH3-binding site at the region of amino acid residues 286-340, where Ser-303, Ser-304, and Ser-328 that are among sev
Protein-phosphoinositide interaction participates in targeting proteins to membranes where they function correctly and is often modulated by phosphorylation of lipids. Here we show that protein phosphorylation of p47(phox), a cytoplasmic activator of the microbicidal phagocyte oxidase (phox), elicits interaction of p47(phox) with phosphoinositides. Although the isolated phox homology (PX) domain of p47(phox) can interact directly with phosphoinositides, the lipid-binding activity of this protein
he transforming growth factor- (TGF-) superfamily proteins, comprising more than 40 members (broadly divided into the TGF-s/activins/nodal family and the bone morphogenetic proteins [BMPs]/Mu ¨llerrian inhibiting substance/growth and differentiation factors [GDFs] family), were originally identified as molecules important for regulating development, differentiation, and tissue repair in various organs. 1 TGF-1, a founding member of the TGF- superfamily, plays a key role in mediating cardiac
Nox1 is highly expressed in the endothelial cells of the cerebral arteries along with Nox2 and Nox4, and the endothelial NAD(P)H oxidase of the cerebral arteries may have a unique activation mechanism by the phagocyte-type cytosolic components.
These findings suggest that insulin resistance is independently associated with poor functional outcome after acute ischemic stroke apart from the risk of short-term stroke recurrence or mortality.
It has been established that oxidative stress plays a crucial role in the development and progression of vascular diseases. Besides the mitochondria, the NADPH oxidase/Nox family proteins are now thought to be important origins of the reactive oxygen species that underlie various vascular disease states, such as hypertension, atherosclerosis, angiogenesis, and ischemia/reperfusion injury. This review summarizes the basis of vascular Nox proteins and discusses their pathophysiological roles in th
Oxidative stress in mitochondria is believed to promote aging. Although passive leakage of electron from the mitochondrial electron transport chain has been considered as a major source of oxidative stress in the heart and the cardiomyocytes therein, enzymes actively producing reactive oxygen species may also exist in mitochondria. We have shown recently that Nox4, a member of the NADPH oxidase family, is localized on intracellular membranes, primarily at mitochondria, in cardiomyocytes. Mitocho
Pericytes are mural cells abundantly present in cerebral microvessels and play important roles, including the formation and maintenance of the blood-brain barrier. Nox4 is a major source of reactive oxygen species in cardiovascular cells and modulate cellular functions, particularly under pathological conditions. In the present study, we found that the expression of Nox4 was markedly induced in microvascular cells, including pericytes, in peri-infarct areas after middle cerebral artery occlusion
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