NADPH oxidases 1 and 4 mediate cellular senescence induced by resveratrol in human endothelial cells

Schilder, Yvonne D.C.; Heiss, Elke H.; Schachner, Daniel; Ziegler, Jürgen; Reznicek, Gottfried; Sorescu, Dan C.; Dirsch, Verena M.

doi:10.1016/j.freeradbiomed.2009.03.013

Cited by 76 publications

(62 citation statements)

References 49 publications

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“…For instance, resveratrol can work as a pro-oxidant under low oxidative conditions, while it becomes an antioxidant under strong oxidative conditions (Gadacha et al, 2009;Giordo et al, 2013). On the other hand, under normal oxidative conditions, the anti-and pro-oxidant behavior of resveratrol appears strictly related to its dosage, being antioxidant at low concentrations and pro-oxidant at higher ones Ladurner et al, 2014;Pasciu et al, 2010;Schilder et al, 2009). In this regard, resveratrol at a concentration of 50 μM, well above our tested dosages, protects HUVECs from ox-LDL-induced oxidative damage (Lefevre et al, 2007), but the effect of these high doses on unstressed cells is so far unknown.…”

Section: Resultsmentioning

confidence: 99%

Resveratrol alters human endothelial cells redox state and causes mitochondrial-dependent cell death

Posadino

Cossu

Giordo

et al. 2015

Food and Chemical Toxicology

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Section: Resultsmentioning

confidence: 99%

Resveratrol alters human endothelial cells redox state and causes mitochondrial-dependent cell death

Posadino

Cossu

Giordo

et al. 2015

Food and Chemical Toxicology

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“…According to this, limited early Nox4-mediated ROS production may be protective because, presumably through Nrf2 and Hif1␣, it may induce antioxidant genes (80). In addition, Nox4 is a mediator of cellular senescence (82) and autophagy (83), both of which were proposed to lessen fibrosis (84,85). However, sustained activation of Nox4 likely contributes to tissue damage and fibrosis.…”

Section: Discussionmentioning

confidence: 99%

Myocardin-related Transcription Factor Regulates Nox4 Protein Expression

Rozycki

Bialik

Speight

et al. 2016

Journal of Biological Chemistry

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Background: Generation of myofibroblasts, the culprit of fibrosis, requires cytoskeleton remodeling and Nox4 (NADPH oxidase) expression. The link between these events is unknown. Results: Down-regulation/inhibition of the cytoskeleton-controlled transcriptional coactivators, myocardin-related transcription factor (MRTF), and TAZ/YAP abrogates Nox4 expression. Conclusion: MRTF and TAZ/YAP are essential for Nox4 expression. Significance: We show new mechanisms whereby the cytoskeleton regulates cellular redox state and fibrogenesis.

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“…Activation of Nox2 requires association with p40 phox , GTP-Rac, p47 phox , and p67 phox (8), and Nox2 is responsible for respiratory burst in AMs (59). Nox4 generates ROS upon association with p22 phox (22) and has been implicated in differentiation (18,19,44,69), cellular senescence (62), and oxygen sensing (43). Nox4 is constitutively active producing H 2 O 2 , but its activity can be augmented by factors that increase its expression or by Poldip2 (48).…”

mentioning

confidence: 99%

Glutathione attenuates ethanol-induced alveolar macrophage oxidative stress and dysfunction by downregulating NADPH oxidases

Yeligar

Harris

Hart

et al. 2014

American Journal of Physiology-Lung Cellular and Molecular Phys

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-Chronic alcohol abuse increases lung oxidative stress and susceptibility to respiratory infections by impairing alveolar macrophage (AM) function. NADPH oxidases (Nox) are major sources of reactive oxygen species in AMs. We hypothesized that treatment with the critical antioxidant glutathione (GSH) attenuates chronic alcohol-induced oxidative stress by downregulating Noxes and restores AM phagocytic function. Bronchoalveolar lavage (BAL) fluid and AMs were isolated from male C57BL/6J mice (8 -10 wk) treated Ϯ ethanol in drinking water (20% wt/vol, 12 wk) Ϯ orally gavaged GSH in methylcellulose vehicle (300 mg·kg Ϫ1 ·day Ϫ1 , during week 12). MH-S cells, a mouse AM cell line, were treated Ϯ ethanol (0.08%, 3 days) Ϯ GSH (500 M, 3 days or last 1 day of ethanol). BAL and AMs were also isolated from ethanol-fed and control mice Ϯ inoculated airway Klebsiella pneumoniae (200 colony-forming units, 28 h) Ϯ orally gavaged GSH (300 mg/kg, 24 h). GSH levels (HPLC), Nox mRNA (quantitative RT-PCR) and protein levels (Western blot and immunostaining), oxidative stress (2=,7=-dichlorofluorescein-diacetate and Amplex Red), and phagocytosis (Staphylococcus aureus internalization) were measured. Chronic alcohol decreased GSH levels, increased Nox expression and activity, enhanced oxidative stress, impaired phagocytic function in AMs in vivo and in vitro, and exacerbated K. pneumonia-induced oxidative stress. Although how oral GSH restored GSH pools in ethanol-fed mice is unknown, oral GSH treatments abrogated the detrimental effects of chronic alcohol exposure and improved AM function. These studies provide GSH as a novel therapeutic approach for attenuating alcohol-induced derangements in AM Nox expression, oxidative stress, dysfunction, and risk for pneumonia. glutathione; alveolar macrophage; nicotinamide adenine dinucleotide phosphate oxidases; oxidative stress; phagocytic function CHRONIC ALCOHOL ABUSE INCREASES susceptibility to acute respiratory distress syndrome (ARDS) (54), a severe form of lung injury with a 26% mortality rate (23), and increases risk of developing respiratory infections, such as pneumonia (49). ARDS is characterized by the development of pulmonary inflammation and edema in response to aspiration, sepsis, or trauma, resulting in systemic proinflammatory cascade activation (68). Compared with a 22% incidence of ARDS in nonalcoholic patients at risk for lung injury, alcoholic patients have a 43% incidence of ARDS (52). Alcohol predisposes to ARDS development through multiple mechanisms, including oxidative stress (11,33,35,37,52). Furthermore, subjects with a history of alcohol use disorders have a higher prevalence of community-acquired pneumonia (20), resulting in worse clinical outcomes than nonalcoholics. Chronic alcohol ingestion increases oxidative stress, which primes the lung for respiratory infections and injury (34).Chronic alcohol consumption depleted levels of the critical antioxidant glutathione (GSH) in the bronchoalveolar lavage (BAL) fluid of human subjects (53) and in the alveolar macro...

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NADPH oxidases 1 and 4 mediate cellular senescence induced by resveratrol in human endothelial cells

Cited by 76 publications

References 49 publications

Resveratrol alters human endothelial cells redox state and causes mitochondrial-dependent cell death

Resveratrol alters human endothelial cells redox state and causes mitochondrial-dependent cell death

Myocardin-related Transcription Factor Regulates Nox4 Protein Expression

Glutathione attenuates ethanol-induced alveolar macrophage oxidative stress and dysfunction by downregulating NADPH oxidases

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