Redox-mediated signal transduction by cardiovascular Nox NADPH oxidases

Brandes, Ralf P.; Weißmann, Norbert; Schröder, Katrin

doi:10.1016/j.yjmcc.2014.02.006

Cited by 86 publications

(59 citation statements)

References 142 publications

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“…We indeed previously demonstrated that in cerebral arteries isolated from young and healthy mice, eNOS was physiologically uncoupled and that H 2 O 2 derived from eNOS activity was an EDRF in these arteries (10). This uncoupling of eNOS was not due to low levels of the cofactor BH 4 and did not favor the monomer configuration of eNOS, both conditions observed during pathological eNOS uncoupling (10). In addition, we previously demonstrated that this eNOS-derived H 2 O 2 -dependent response was absent in cerebral arteries from eNOS Ϫ/Ϫ mice and was also absent in peripheral arteries such as gracilis arteries, showing that this apparent eNOS uncoupling was specific to the cerebrovasculature (10).…”

Section: Discussionmentioning

confidence: 79%

Knockdown of angiopoietin like-2 protects against angiotensin II-induced cerebral endothelial dysfunction in mice

Luo

Duquette

et al. 2015

American Journal of Physiology-Heart and Circulatory Physiology

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) is a circulating pro-inflammatory and pro-oxidative protein, but its role in regulating cerebral endothelial function remains unknown. We hypothesized that in mice knockdown (KD) of angptl2, cerebral endothelial function would be protected against ANG II-induced damage. Subcutaneous infusion of ANG II (200 ng·kg Ϫ1 ·min Ϫ1 , n ϭ 15) or saline (n ϭ 15) was performed in 20-wk-old angptl2 KD mice and wild-type (WT) littermates for 14 days. In saline-treated KD and WT mice, the amplitude and the sensitivity of ACh-induced dilations of isolated cerebral arteries were similar. However, while endothelial nitric oxide (NO) synthase (eNOS)-derived O 2 Ϫ /H2O2 contributed to dilation in WT mice, eNOS-derived NO (P Ͻ 0.05) was involved in KD mice. ANG II induced cerebral endothelial dysfunction only in WT mice (P Ͻ 0.05), which was reversed (P Ͻ 0.05) by either N-acetyl-L-cysteine, apocynin, gp91ds-tat, or indomethacin, suggesting the contribution of reactive oxygen species from Nox2 and Cox-derived contractile factors. In KD mice treated with ANG II, endothelial function was preserved, likely via Nox-derived H 2O2, sensitive to apocynin and PEG-catalase (P Ͻ 0.05), but not to gp91ds-tat. In the aorta, relaxation similarly and essentially depended on NO; endothelial function was maintained after ANG II infusion in all groups, but apocynin significantly reduced aortic relaxation in KD mice (P Ͻ 0.05). Protein expression levels of Nox1/2 in cerebral arteries were similar among all groups, but that of Nox4 was greater (P Ͻ 0.05) in saline-treated KD mice. In conclusion, knockdown of angptl2 may be protective against ANG II-induced cerebral endothelial dysfunction; it favors the production of NO, likely increasing endothelial cell resistance to stress, and permits the expression of an alternative vasodilatory Nox pathway.angiopoietin like-2; endothelium; cerebral arteries; nitric oxide; NA-DPH oxidases CARDIOVASCULAR DISEASES, INCLUDING stroke, affect more than 50% of the world population today and remain an unresolved clinical issue. Inflammation and oxidative stress synergize to promote endothelial damage, thereby chronically driving atherogenesis (13,14). Importantly, the cerebral vascular endothelium is highly sensitive to this deleterious environment (8, 11). Reactive oxygen species (ROS) are signaling molecules generated by the electron transport chain (35) and are by-products of enzymes including the NADPH oxidases (18), xanthine oxidases, and uncoupled endothelial nitric oxide (NO) synthase (eNOS) (19,28). In parallel, they trigger an innate anti-oxidative system to prevent their potential harmful effects (26,29). When this system is overwhelmed, however, endothelial damages occur and dysfunction develops, which are the first steps toward atherogenesis.Recently, a protein identified as angiopoietin like-protein 2 (angptl2), a member of the greater angiopoietin-like family and derived from various cell types including adipocytes (31) and endothelial cells (12), has been implicated in a number of chronic inflammatory d...

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Section: Discussionmentioning

confidence: 79%

Knockdown of angiopoietin like-2 protects against angiotensin II-induced cerebral endothelial dysfunction in mice

Luo

Duquette

et al. 2015

American Journal of Physiology-Heart and Circulatory Physiology

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show abstract

“…ROS were once recognized as endogenous pathogenic molecules in cellular injury due to the damage they inflict on lipids, proteins, and DNA in cells [12,13] . However, ROS have now [14,15] . Only under pathological conditions, for various reasons, are the formation and elimination of ROS disturbed and excessive ROS generated; the elevated ROS levels induce a condition called oxidative stress and inflict cell and tissue damage.…”

Section: Introductionmentioning

confidence: 99%

N-acetylcysteine alleviates angiotensin II-mediated renal fibrosis in mouse obstructed kidneys

Shen

Miao

et al. 2016

Acta Pharmacol Sin

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Aim: To investigate the effects of ROS scavenger N-acetylcysteine (NAC) on angiotensin II (Ang II)-mediated renal fibrosis in vivo and in vitro. Methods: Mice were subjected to unilateral ureteral obstruction (UUO), and then treated with vehicle or NAC (250 mg/kg, ip) for 7 days. Histological changes of the obstructed kidneys were observed with Masson's trichrome staining. ROS levels were detected with DHE staining. The expression of relevant proteins in the obstructed kidneys was assessed using Western blotting assays. Cultured rat renal fibroblast NRK-49F cells were used for in vitro experiments. Results: In the obstructed kidneys, Ang II levels were significantly elevated, and collagen I was accumulated in the interstitial spaces. Furthermore, ROS production and the expression of p47 (a key subunit of NADPH oxidase complexes) were increased in a timedependent manner; the expression of fibronectin, α-SMA and TGF-β were upregulated. Administration of NAC significantly alleviated the fibrotic responses in the obstructed kidneys. In cultured NRK-49F cells, treatment with Ang II (0.001-10 μmol/L) increased the expression of fibronectin, collagen I, α-SMA and TGF-β in dose-dependent and time-dependent manners. Ang II also increased ROS production and the phosphorylation of Smad3. Pretreatment with NAC (5 μmol/L) blocked Ang II-induced oxidative stress and ECM production in the cells. Conclusion: In mouse obstructed kidneys, the fibrotic responses result from Ang II upregulation can be alleviated by the ROS scavenger N-acetylcysteine.

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“…The NADPH oxidase NOX family has the function of generating reactive oxygen species. Some NOX enzymes can express relatively high tissue characteristics and generate the hormone or tissue components required to generate reactive oxygen species which cause cardiovascular disease and chronic liver/hepatitis cancer (Brandes et al, 2014;Choi et al, 2014). Most endogenous reactive oxygen species are generated in the mitochondrial respiratory chain; Romo1 is present in the mitochondrion and its protein increases by oxidation stimulation, thus causing the occurrence of diseases (Na et al, 2008;Chung et al, 2012).…”

Section: Resultsmentioning

confidence: 99%

In vitro free radicals scavenging activity and antioxidant capacity of solid-state fermented wheat bran and its potential modulation of antioxidative molecular targets in chicken PBMC

Wang

Chang

et al. 2016

R. Bras. Zootec.

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-The purpose of this study was to demonstrate the in vitro free radical scavenging activity and antioxidant capacity in solid-state fermented wheat bran and its potential modulation of antioxidative molecular targets in chicken peripheral blood mononuclear cells (PBMC). After solid-state fermentation of wheat bran by white rot fungi for 12 d, the scavenging action of the fermented wheat bran extracts was 1, 1-diphenyl-2-picrylhydrazyl (DPPH), and the free radicals increased significantly, approximately 1.5-fold. Trolox equivalent antioxidant capacity of 1 mg/mL fermented wheat bran extracts was increased from 100 to 150 mM trolox antioxidant capacity after 12 d of fermentation. Moreover, the extracts exhibited 50% of the chelating capacity observed for ferrous iron (Fe2+) after fermenting for 12 d. In vitro, and under the stimulus of fermented wheat bran, the antioxidant gene expression (GST, HO-1, Nrf2, and GCLC genes) of PBMC was more than double that of the PBS, ascorbic acid, and unfermented wheat bran. The expression of fermented wheat bran was the lowest for the NOX1 and ROMO1 genes. Solid-state wheat bran fermented by white rot fungi can increase the scavenging action of DPPH, the trolox equivalent antioxidant capacity, and the chelating capacity of ferrous iron; in addition, in vitro, it can regulate the expression of antioxidant molecular targets in chicken PBMC.

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Redox-mediated signal transduction by cardiovascular Nox NADPH oxidases

Cited by 86 publications

References 142 publications

Knockdown of angiopoietin like-2 protects against angiotensin II-induced cerebral endothelial dysfunction in mice

Knockdown of angiopoietin like-2 protects against angiotensin II-induced cerebral endothelial dysfunction in mice

N-acetylcysteine alleviates angiotensin II-mediated renal fibrosis in mouse obstructed kidneys

In vitro free radicals scavenging activity and antioxidant capacity of solid-state fermented wheat bran and its potential modulation of antioxidative molecular targets in chicken PBMC

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