scholarly journals Nox4-derived reactive oxygen species mediate cardiomyocyte injury in early type 1 diabetes

2012 ◽  
Vol 302 (3) ◽  
pp. C597-C604 ◽  
Author(s):  
Rita M. Maalouf ◽  
Assaad A. Eid ◽  
Yves C. Gorin ◽  
Karen Block ◽  
Gladys Patricia Escobar ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Type 1 Diabetes ◽  
Molecular Markers ◽  
Nadph Oxidase ◽  
Diabetic Cardiomyopathy ◽  
Oxidase Activity ◽  
Diabetic Rats ◽  
Oxygen Species ◽  
Nadph Oxidase Activity

Oxidative stress contributes to diabetic cardiomyopathy. This study explored the role of the NADPH oxidase Nox4 as a source of reactive oxygen species (ROS) involved in the development of diabetic cardiomyopathy. Phosphorothioated antisense (AS) or sense (S) oligonucleotides for Nox4 were administered for 2 wk to rats made diabetic by streptozotocin. NADPH oxidase activity, ROS generation, and the expression of Nox4, but Nox1 or Nox2, were increased in left ventricular tissue of the diabetic rats. Expression of molecular markers of hypertrophy and myofibrosis including fibronectin, collagen, α-smooth muscle actin, and β-myosin heavy chain were also increased. These parameters were attenuated by the administration of AS but not S Nox4. Moreover, the impairment of contractility observed in diabetic rats was prevented in AS- but not S-treated animals. Exposure of cultured cardiac myocytes to 25 mM glucose [high glucose (HG)] increased NADPH oxidase activity, the expression of Nox4, and molecular markers of cardiac injury. These effects of HG were prevented in cells infected with adenoviral vector containing a dominant negative form of Nox4. This study provides strong evidence that Nox4 is an important source of ROS in the left ventricle and that Nox4-derived ROS contribute to cardiomyopathy at early stages of type 1 diabetes.

scholarly journals NADPH Oxidase-Derived Overproduction of Reactive Oxygen Species Impairs Postischemic Neovascularization in Mice with Type 1 Diabetes

2006 ◽  
Vol 169 (2) ◽  
pp. 719-728 ◽  
Author(s):  
Téni G Ebrahimian ◽  
Christophe Heymes ◽  
Dong You ◽  
Olivier Blanc-Brude ◽  
Barend Mees ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Type 1 Diabetes ◽  
Nadph Oxidase ◽  
Reactive Oxygen ◽  
Oxygen Species

scholarly journals Overexpression of Ras-Related C3 Botulinum Toxin Substrate 2 Radiosensitizes Melanoma Cells In Vitro and In Vivo

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Wentao Hu ◽  
Lin Zhu ◽  
Weiwei Pei ◽  
Shuxian Pan ◽  
Ziyang Guo ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Botulinum Toxin ◽  
Malignant Melanoma ◽  
Nadph Oxidase ◽  
Oxidase Activity ◽  
Melanoma Cells ◽  
Oxygen Species ◽  
X Rays ◽  
Nadph Oxidase Activity ◽  
Carbon Ion

Radioresistance is the major obstacle in the radiotherapy of the malignant melanoma. Thus, it is of importance to increase the radiosensitivity of melanoma cells. In the present study, the radioresistant melanoma cell line OCM-1 with inducible overexpression of Ras-related C3 botulinum toxin substrate 2 was established based on a radiation-inducible early growth response gene (Egr-1) promoter. The effects of Ras-related C3 botulinum toxin substrate 2 overexpression on the radiosensitivity of melanoma cells exposed to either X-rays or carbon ion beams were evaluated in cultured cells as well as xenograft tumor models. In addition, both reactive oxygen species yield and the NADPH oxidase activity were measured in the irradiated melanoma cells. It was found that the radiation-inducible overexpression of Ras-related C3 botulinum toxin substrate 2 sensitized the melanoma cells to both X-rays and carbon ion irradiation by enhancing the NADPH oxidase activity and the subsequent reactive oxygen species production. Besides, the overexpression of Ras-related C3 botulinum toxin substrate 2 enhanced the tumor-killing effect of radiotherapy in xenograft tumors significantly. The results of this study indicate that Ras-related C3 botulinum toxin substrate 2 is promising in increasing the radiosensitivity of melanoma cells, which provides experimental evidence and theoretical basis for clinical radiosensitization of the malignant melanoma.

scholarly journals Renin Inhibition Attenuates Insulin Resistance, Oxidative Stress, and Pancreatic Remodeling in the Transgenic Ren2 Rat

Endocrinology ◽  
2008 ◽  
Vol 149 (11) ◽  
pp. 5643-5653 ◽  
Author(s):  
Javad Habibi ◽  
Adam Whaley-Connell ◽  
Melvin R. Hayden ◽  
Vincent G. DeMarco ◽  
Rebecca Schneider ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Reactive Oxygen Species ◽  
Nadph Oxidase ◽  
Oxidase Activity ◽  
Renin Angiotensin System ◽  
Oxygen Species ◽  
Ang Ii ◽  
Angiotensin System ◽  
Nadph Oxidase Activity ◽  
Renin Inhibition

Emerging evidence indicates that pancreatic tissue expresses all components of the renin-angiotensin system. However, the functional role is not well understood. This investigation examined renin inhibition on pancreas structure/function in the transgenic Ren2 rat harboring the mouse renin gene, a model of tissue renin overexpression. Renin is the rate-limiting step in the generation of angiotensin II (Ang II), which stimulates the generation of reactive oxygen species in a variety of tissues. Overexpression of renin in Ren2 rats results in hypertension, insulin resistance, and cardiovascular and renal damage. Young (6–7 wk old) insulin-resistant male Ren2 and age-matched insulin sensitive Sprague Dawley rats were treated with the renin inhibitor, aliskiren (50 mg/kg·d by ip injection), or placebo for 21 d. At 21 d, the Ren2 demonstrated insulin resistance with increased islet insulin, Ang II, and reduced total insulin receptor substrate (IRS)-1, IRS-2, and Akt immunostaining. There was increased islet nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity and subunits (p47phox and Rac1) as well as increased nitrotyrosine immunostaining (each P < 0.05). These functional abnormalities were associated with a disordered islet architecture; increased islet-exocrine interface, pericapillary fibrosis, and structurally abnormal mitochondria and content in endocrine and exocrine pancreas. In vivo treatment with aliskiren normalized systemic insulin resistance and islet insulin, Ang II, NADPH oxidase activity/subunits, and nitrotyrosine and improved total IRS-1 and Akt phosphorylation (each P < 0.05) as well as islet/exocrine structural abnormalities. Collectively, these data suggest that pancreatic functional/structural changes are driven, in part, by tissue renin-angiotensin system-mediated increases in NADPH oxidase and reactive oxygen species generation, abnormalities attenuated with direct renin inhibition.

Induction of NADPH oxidase activity and reactive oxygen species production by a single Trypanosoma cruzi antigen

2010 ◽  
Vol 40 (13) ◽  
pp. 1531-1538 ◽  
Author(s):  
Natalia Guiñazú ◽  
Eugenio Antonio Carrera-Silva ◽  
María Cecilia Becerra ◽  
Andrea Pellegrini ◽  
Inés Albesa ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Trypanosoma Cruzi ◽  
Nadph Oxidase ◽  
Oxidase Activity ◽  
Reactive Oxygen Species Production ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Nadph Oxidase Activity ◽  
Species Production

D5 dopamine receptor regulation of reactive oxygen species production, NADPH oxidase, and blood pressure

2006 ◽  
Vol 290 (1) ◽  
pp. R96-R104 ◽  
Author(s):  
Zhiwei Yang ◽  
Laureano D. Asico ◽  
Peiying Yu ◽  
Zheng Wang ◽  
John E. Jones ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Reactive Oxygen Species ◽  
Nadph Oxidase ◽  
Oxidase Activity ◽  
Reactive Oxygen ◽  
Receptor Activation ◽  
Oxidase Inhibitor ◽  
Ros Production ◽  
Oxygen Species ◽  
Nadph Oxidase Activity

Activation of D1-like receptors (D1 and/or D5) induces antioxidant responses; however, the mechanism(s) involved in their antioxidant actions are not known. We hypothesized that stimulation of the D5 receptor inhibits NADPH oxidase activity, and thus the production of reactive oxygen species (ROS). We investigated this issue in D5 receptor-deficient (D5−/−) and wild-type (D5+/+) mice. NADPH oxidase protein expression (gp91phox, p47phox, and Nox 4) and activity in kidney and brain, as well as plasma thiobarbituric acid-reactive substances (TBARS) were higher in D5−/− than in D5+/+ mice. Furthermore, apocynin, an NADPH oxidase inhibitor, normalized blood pressure, renal NADPH oxidase activity, and plasma TBARS in D5−/− mice. In HEK-293 cells that heterologously expressed human D5 receptor, its agonist fenoldopam decreased NADPH oxidase activity, expression of one of its subunits (gp91phox), and ROS production. The inhibitory effect of the D5 receptor activation on NADPH oxidase activity was independent of cAMP/PKA but was partially dependent on phospholipase D2. The ability of D5 receptor stimulation to decrease ROS production may explain, in part, the antihypertensive action of D5 receptor activation.

Curcumin and resveratrol act by different ways on NADPH oxidase activity and reactive oxygen species produced by equine neutrophils

2013 ◽  
Vol 206 (2) ◽  
pp. 186-193 ◽  
Author(s):  
Sandrine Derochette ◽  
Thierry Franck ◽  
Ange Mouithys-Mickalad ◽  
Justine Ceusters ◽  
Ginette Deby-Dupont ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Nadph Oxidase ◽  
Oxidase Activity ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Nadph Oxidase Activity

Reactive Oxygen Species-Mediated Homologous Downregulation of Angiotensin II Type 1 Receptor Mrna by Angiotensin II

Hypertension ◽  
2000 ◽  
Vol 36 (suppl_1) ◽  
pp. 688-688
Author(s):  
Toshihiro Ichiki ◽  
Kotaro Takeda ◽  
Akira Takeshita
Keyword(s):  
Reactive Oxygen Species ◽  
Angiotensin Ii ◽  
Nadph Oxidase ◽  
Mrna Expression ◽  
Crucial Role ◽  
Oxygen Species ◽  
Ang Ii ◽  
Stimulation Of

58 Recent studies suggest a crucial role of reactive oxygen species (ROS) for the signaling of Angiotensin II (Ang II) through type 1 Ang II receptor (AT1-R). However, the role of ROS in the regulation of AT1-R expression has not been explored. In this study, we examined the effect of an antioxidant on the homologous downregulation of AT1-R by Ang II. Ang II (10 -6 mol/L) decreased AT1-R mRNA with a peak suppression at 6 hours of stimulation in rat aortic vascular smooth muscle cells (VSMC). Ang II dose-dependently (10 -8 -10 -6 ) suppressed AT1-R mRNA at 6 hours of stimulation. Preincubation of VSMC with N-acetylcysteine (NAC), a potent antioxidant, almost completely inhibited the Ang II-induced downregulation of AT1-R mRNA. The effect of NAC was due to stabilization of the AT1-R mRNA that was destabilized by Ang II. Ang II did not affect the promoter activity of AT1-R gene. Diphenylene iodonium (DPI), an inhibitor of NADH/NADPH oxidase failed to inhibit the Ang II-induced AT1-R mRNA downregulation. The Ang II-induced AT1-R mRNA downregulation was also blocked by PD98059, an extracellular signal-regulated protein kinase (ERK) kinase inhibitor. Ang II-induced ERK activation was inhibited by NAC as well as PD98059 whereas DPI did not inhibit it. To confirm the role of ROS in the regulation of AT1-R mRNA expression, VSMC were stimulated with H 2 O 2 . H 2 O 2 suppressed the AT1-R mRNA expression and activated ERK. These results suggest that production of ROS and activation of ERK are critical for downregulation of AT1-R mRNA. The differential effect of NAC and DPI on the downregulation of AT1-R mRNA may suggest the presence of other sources than NADH/NADPH oxidase pathway for ROS in Ang II signaling. Generation of ROS through stimulation of AT1-R not only mediates signaling of Ang II but may play a crucial role in the adaptation process of AT1-R to the sustained stimulation of Ang II.

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