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)

Adiponectin (also known as 30-kDa adipocyte complement-related protein or Acrp30) is an abundant adipocyte-derived plasma protein with anti-atherosclerotic and insulin-sensitizing properties. In order to investigate the potential mechanism(s) of the vascular protective effect of adiponectin, we used cultured bovine endothelial cells (BAECs) to study the effect of recombinant globular adiponectin (gAd) on cellular proliferation and the generation of reactive oxygen species (ROS) induced by oxidized LDL (oxLDL). By RT-PCR, we found that BAECs preferentially express AdipoR1, the high-affinity receptor for gAd. Treatment of BAECs with oxLDL (10 microg/ml) for 16h stimulated cell proliferation by approximately 60%, which was inhibited by co-incubation with gAd. Cell treatment with gAd also inhibited basal and oxLDL-induced superoxide release, and suppressed the activation of p42/p44 MAP kinase by oxLDL. The effects of gAd were blocked by a specific polyclonal anti-adiponectin antibody (TJ414). OxLDL-induced BAEC proliferation and superoxide release were inhibited by the NAD(P)H oxidase inhibitor diphenyleneiodonium (DPI), but not the eNOS inhibitor l-nitroarginine methyl ester (l-NAME). Finally, gAd ameliorated the suppression of eNOS activity by oxLDL. These data indicate that gAd inhibits oxLDL-induced cell proliferation and suppresses cellular superoxide generation, possibly through an NAD(P)H oxidase-linked mechanism.
...
PMID:Adiponectin suppresses proliferation and superoxide generation and enhances eNOS activity in endothelial cells treated with oxidized LDL. 1476 3

Obesity is a principal causative factor in the development of metabolic syndrome. Here we report that increased oxidative stress in accumulated fat is an important pathogenic mechanism of obesity-associated metabolic syndrome. Fat accumulation correlated with systemic oxidative stress in humans and mice. Production of ROS increased selectively in adipose tissue of obese mice, accompanied by augmented expression of NADPH oxidase and decreased expression of antioxidative enzymes. In cultured adipocytes, elevated levels of fatty acids increased oxidative stress via NADPH oxidase activation, and oxidative stress caused dysregulated production of adipocytokines (fat-derived hormones), including adiponectin, plasminogen activator inhibitor-1, IL-6, and monocyte chemotactic protein-1. Finally, in obese mice, treatment with NADPH oxidase inhibitor reduced ROS production in adipose tissue, attenuated the dysregulation of adipocytokines, and improved diabetes, hyperlipidemia, and hepatic steatosis. Collectively, our results suggest that increased oxidative stress in accumulated fat is an early instigator of metabolic syndrome and that the redox state in adipose tissue is a potentially useful therapeutic target for obesity-associated metabolic syndrome.
...
PMID:Increased oxidative stress in obesity and its impact on metabolic syndrome. 1559

Endothelial dysfunction is one manifestation of the many changes induced in the arterial wall by the metabolic abnormalities accompanying diabetes and insulin resistance. In type 1 diabetes, endothelial dysfunction is most consistently found in advanced stages of the disease. In other patients, it is associated with nondiabetic insulin resistance and probably precedes type 2 diabetes. In obesity and insulin resistance, increased secretion of proinflammatory cytokines and decreased secretion of adiponectin from adipose tissue, increased circulating levels of free fatty acids, and postprandial hyperglycemia can all alter gene expression and cell signaling in vascular endothelium, cause vascular insulin resistance, and change the release of endothelium-derived factors. In diabetes, sustained hyperglycemia causes increased intracellular concentrations of glucose metabolites in endothelial cells. These changes cause mitochondrial dysfunction, increased oxidative stress, and activation of protein kinase C. Dysfunctional endothelium displays activation of vascular NADPH oxidase, uncoupling of endothelial nitric oxide synthase, increased expression of endothelin 1, a changed balance between the production of vasodilator and vasoconstrictor prostanoids, and induction of adhesion molecules. This review describes how these and other changes influence endothelium-dependent vasodilation in patients with insulin resistance and diabetes. The clinical utility of endothelial function testing and future therapeutic targets is also discussed.
...
PMID:Mechanisms of Disease: endothelial dysfunction in insulin resistance and diabetes. 1717 29

Increased albuminuria is associated with obesity and diabetes and is a risk factor for cardiovascular and renal disease. However, the link between early albuminuria and adiposity remains unclear. To determine whether adiponectin, an adipocyte-derived hormone, is a communication signal between adipocytes and the kidney, we performed studies in a cohort of patients at high risk for diabetes and kidney disease as well as in adiponectin-knockout (Ad(-/-)) mice. Albuminuria had a negative correlation with plasma adiponectin in obese patients, and Ad(-/-) mice exhibited increased albuminuria and fusion of podocyte foot processes. In cultured podocytes, adiponectin administration was associated with increased activity of AMPK, and both adiponectin and AMPK activation reduced podocyte permeability to albumin and podocyte dysfunction, as evidenced by zona occludens-1 translocation to the membrane. These effects seemed to be caused by reduction of oxidative stress, as adiponectin and AMPK activation both reduced protein levels of the NADPH oxidase Nox4 in podocytes. Ad(-/-) mice treated with adiponectin exhibited normalization of albuminuria, improvement of podocyte foot process effacement, increased glomerular AMPK activation, and reduced urinary and glomerular markers of oxidant stress. These results suggest that adiponectin is a key regulator of albuminuria, likely acting through the AMPK pathway to modulate oxidant stress in podocytes.
...
PMID:Adiponectin regulates albuminuria and podocyte function in mice. 1843 7

This work represents a maiden effort to systematically screen the transcriptome of the healing wound-edge tissue temporally using high-density GeneChips. Changes during the acute inflammatory phase of murine excisional wounds were characterized histologically. Sets of genes that significantly changed in expression during healing could be segregated into the following five sets: up-early (6-24 h; cytokine-cytokine receptor interaction pathway), up-intermediary (12-96 h; leukocyte-endothelial interaction pathway), up-late (48-96 h; cell-cycle pathway), down-early (6-12 h; purine metabolism) and down-intermediary (12-96 h; oxidative phosphorylation pathway). Results from microarray and real-time PCR analyses were consistent. Results listing all genes that were significantly changed at any specific time point were further mined for cell-type (neutrophils, macrophages, endothelial, fibroblasts, and pluripotent stem cells) specificity. Candidate genes were also clustered on the basis of their functional annotation, linking them to inflammation, angiogenesis, reactive oxygen species (ROS), or extracellular matrix (ECM) categories. Rapid induction of genes encoding NADPH oxidase subunits and downregulation of catalase in response to wounding is consistent with the fact that low levels of endogenous H2O2 is required for wound healing. Angiogenic genes, previously not connected to cutaneous wound healing, that were induced in the healing wound-edge included adiponectin, epiregulin, angiomotin, Nogo, and VEGF-B. This study provides a digested database that may serve as a valuable reference tool to develop novel hypotheses aiming to elucidate the biology of cutaneous wound healing comprehensively.
...
PMID:Characterization of the acute temporal changes in excisional murine cutaneous wound inflammation by screening of the wound-edge transcriptome. 1846 Jun 41

We have recently shown 1alpha,25-dihydroxycholecalciferol increased oxidative stress and inflammatory stress in vitro, whereas suppression of 1alpha,25-dihydroxycholecalciferol with dietary calcium (Ca) decreased oxidative and inflammatory stress in vivo. However, dairy products contains additional factors, such as angiotensin-converting enzyme inhibitors, which may further suppress oxidative and inflammatory stress. Accordingly, this study was designed to study the effects of the short-term (3 wk) basal suboptimal Ca (0.4%), high-Ca (1.2% from CaCO(3)), and high-dairy (1.2% Ca from milk) obesigenic diets on oxidative and inflammatory stress in adipocyte fatty acid-binding protein-agouti transgenic mice. Adipose tissue reactive oxygen species (ROS) production and NADPH oxidase mRNA and plasma malondialdehyde (MDA) were reduced by the high-Ca diet (P < 0.001) compared with the basal diet and ROS and MDA were further decreased by the high-dairy diet (P < 0.001). The high-Ca and -dairy diets also resulted in suppression of adipose tissue tumor necrosis factor alpha and interleukin (IL)-6 mRNA (P = 0.001) compared with the basal diet, whereas an inverse pattern was noted for adiponectin and IL-15 mRNA (P = 0.002). Consequently, we conducted a follow-up evaluation of adiponectin and C-reactive protein (CRP) in archival samples from 2 previous clinical trials conducted in obese men and women. Twenty-four weeks of feeding a high-dairy eucaloric diet and hypocaloric diet resulted in an 11 (P < 0.03) and 29% (P < 0.01) decrease in CRP, respectively (post-test vs. pre-test), whereas there was no significant change in the low-dairy groups. Adiponectin decreased by 8% in subjects fed the eucaloric high-dairy diet (P = 0.003) and 18% in those fed the hypocaloric high-dairy diet (P < 0.05). These data demonstrate that dietary Ca suppresses adipose tissue oxidative and inflammatory stress.
...
PMID:Dietary calcium and dairy products modulate oxidative and inflammatory stress in mice and humans. 1849 32

Studies reported the effects of polyphenols but not for grape polyphenols towards obesity. We analysed the effects of a polyphenolic grape seed extract (GSE) on obesity and oxidative stress in hamsters receiving a high-fat diet (HFD). Three groups of hamsters received a standard diet (STD), or a HFD plus a daily gavage with water (Control, HFD) or a solution of GSE (HFD + GSE) for 12 wk. Plasma glucose, triglycerides (TG), insulin, leptin and adiponectin were measured. Oxidative stress was assessed by cardiac production of superoxide anion and NAD(P)H oxidase expression. After 12 wk, HFD increased abdominal fat as compared with standards. GSE avoided this feature. HFD led to higher plasma glucose, TG, insulin and greater insulin resistance (HOMA-IR) values. GSE prevented in part these effects, reducing insulinemia and leptinemia by 16.5 and 45%, respectively, whereas adiponectin level increased by 61% compared with obese controls. GSE lowered glycemia and HOMA-IR and strongly prevented cardiac production of superoxide by 74% and NAD(P)H oxidase expression by 30%. This is the first time that chronic consumption of grape phenolics is shown to reduce obesity development and related metabolic pathways including adipokine secretion and oxidative stress.
...
PMID:Chardonnay grape seed procyanidin extract supplementation prevents high-fat diet-induced obesity in hamsters by improving adipokine imbalance and oxidative stress markers. 1903 54

Previous study showed that mulberry (Morus Alba L.) leaf (ML) ameliorates atherosclerosis in apoE(-/-) mice. Although the adipocytokine dysregulation is an important risk factor for atherosclerotic cardiovascular disease, the effect of ML on metabolic disorders related to adipocytokine dysregulation and inflammation has not been studied. Therefore, we studied the effects of ML in metabolic disorders and examined the mechanisms by which ML ameliorates metabolic disorders in db/db mice. We treated db/db mice with ML, pioglitazone, or both for 12 weeks and found that ML decreased blood glucose and plasma triglyceride. Co-treatment with ML and pioglitazone showed additive effects compared with pioglitazone. Moreover, their co-treatment attenuated the body weight increase observed under the pioglitazone treatment. ML treatment also increased the expression of adiponectin, and decreased the expression of TNF-alpha, MCP-1, and macrophage markers in white adipose tissue (WAT). Furthermore, ML decreased lipid peroxides and the expression of NADPH oxidase subunits in WAT and liver. Their co-treatment enhanced these effects. Thus, ML ameliorates adipocytokine dysregulation at least in part through inhibiting oxidative stress in WAT of db/db mice, and that ML may be a basis for a pharmaceutical for the treatment of the metabolic syndrome as well as reducing adverse effects of pioglitazone.
...
PMID:Mulberry leaf ameliorates the expression profile of adipocytokines by inhibiting oxidative stress in white adipose tissue in db/db mice. 1907 Aug 57

Globular adiponectin (gAd) induces the generation of reactive oxygen species (ROS) and nitric oxide (NO) in the murine macrophage cell line RAW 264. We investigated the role of Ca(2+) in gAd-induced ROS and NO generation. Pretreatment with BAPTA-AM, a selective chelator of intracellular Ca(2+) ([Ca(2+)](i)), partially reduced gAd-induced generation of ROS and NO in gAd-treated RAW 264 cells. The lowest [Ca(2+)](i) occurred 30min after gAd treatment, after which [Ca(2+)](i) increased continually and exceeded the initial level. The mitochondrial Ca(2+) ([Ca(2+)](m)) detected by Rhod-2 fluorescence started to increase at 6h after gAd treatment. Pretreatment with a NAD(P)H oxidase inhibitor, diphenyleneiodonium, prevented the reduction of [Ca(2+)](i) in the early phase after gAd treatment. Calcium depletion by BAPTA-AM had no effect on the gAd-induced [Ca(2+)](m) oscillation. The administration of a specific calmodulin inhibitor, calmidazolium, significantly suppressed gAd-induced ROS and NO generation and NOS activity.
...
PMID:Involvement of Ca(2+) in globular adiponectin-induced reactive oxygen species. 1924 86

We investigated differences in aortic endothelial function among young (5 months) and old (20 months) male or female mice. Aortas isolated from male-old mice exhibited: (a) impaired relaxation to both acetylcholine (ACh) (P<0.01 vs. male-young or female-old) and A23187 (P<0.01 vs. male-young; P<0.001 vs. female-old), but unimpaired relaxation to sodium nitroprusside, and (b) increased superoxide generation (indicated by NBT reduction) (P<0.001 vs. male-young; P<0.01 vs. female-old) and increased 3-nitrotyrosine expression (marker for ONOO(-)) (P<0.01 vs. male-young or female-old). The protein expression of gp91phox, an NAD(P)H oxidase subunit, was upregulated in aortas from old mice (vs. young ones of the same gender) (males P<0.01; females P<0.05). The plasma adiponectin level (P<0.001) and the aortic Cu/Zn-SOD and EC-SOD protein expressions (each, P<0.01) were increased in females (vs. age-matched males). Aortic total SOD activities were lower in male-old than in either male-young (P<0.01) or female-old (P<0.001) mice. In aortas from male-young, female-young, and female-old mice, NADH [NAD(P)H oxidase substrate] and diethyldithiocarbamate (DDC; a SOD inhibitor) (whether applied alone or together) reduced ACh-induced endothelium-dependent relaxation (P<0.01 or P<0.001) and increased ACh-induced superoxide generation (P<0.05 or P<0.001). Tempol (a SOD mimetic) enhanced ACh-induced relaxation (P<0.05) and reduced ACh-induced superoxide generation (P<0.01) only in male-old aortas. These results suggest: (i) the impaired endothelium-dependent aortic relaxation in male-old mice is due to enhanced superoxide production via NADPH oxidase, and (ii) the relative preservation of endothelial function in female-old aortas may be due to enhanced superoxide scavenging (via increases in Cu/Zn-SOD and EC-SOD proteins and total SOD activity).
...
PMID:Gender differences in age-related endothelial function in the murine aorta. 1935 59


1 2 3 4 5 Next >>

---