ArticleBiochemical pharmacology2012
Inhibition of ROS-induced apoptosis in endothelial cells by nitrone spin traps via induction of phase II enzymes and suppression of mitochondria-dependent pro-apoptotic signaling.
Article in Biochemical pharmacology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 51 citations in OpenAlex.
- Nrf2-Mediated Antioxidant Defense and Thyroid Hormone Signaling: A Focus on Cardioprotective Effects.Antioxidants (Basel, Switzerland) · 2023Review
- Geraniin Protects against Cerebral Ischemia/Reperfusion Injury by Suppressing Oxidative Stress and Neuronal Apoptosis via Regulation of the Nrf2/HO-1 Pathway.Oxidative medicine and cellular longevity · 2022Article
- Role of Nrf2 and Its Activators in Cardiocerebral Vascular Disease.Oxidative medicine and cellular longevity · 2020Review
- Ling-Gui-Zhu-Gan Decoction Protects H9c2 Cells against HEvidence-based complementary and alternative medicine : eCAM · 2020Article
- Membrane-specific spin trap, 5-dodecylcarbamoyl-5-N-dodecylacetamide-1-pyroline-N-oxide (diCOrganic & biomolecular chemistry · 2019Article
- Oxidants-Antioxidants Profile in the Breast Cancer Cell Line MCF-7Asian Pacific journal of cancer prevention : APJCP · 2018Article
- Redox Signaling by Reactive Electrophiles and Oxidants.Chemical reviews · 2018Review
- The naturally occurring xanthone α-mangostin induces ROS-mediated cytotoxicity in non-small scale lung cancer cells.Saudi journal of biological sciences · 2018Article
- Oridonin exerts anticancer effect on osteosarcoma by activating PPAR-γ and inhibiting Nrf2 pathway.Cell death & disease · 2018Article
- Nrf2 Deficiency Unmasks the Significance of Nitric Oxide Synthase Activity for Cardioprotection.Oxidative medicine and cellular longevity · 2018Article
- Nitrones reverse hyperglycemia-induced endothelial dysfunction in bovine aortic endothelial cells.Biochemical pharmacology · 2016Article
- Reversal of SIN-1-induced eNOS dysfunction by the spin trap, DMPO, in bovine aortic endothelial cells via eNOS phosphorylation.British journal of pharmacology · 2014Article
- Apoptosis of bone marrow mesenchymal stem cells caused by hypoxia/reoxygenation via multiple pathways.International journal of clinical and experimental medicine · 2014Article
- Apigenin protects endothelial cells from lipopolysaccharide (LPS)-induced inflammation by decreasing caspase-3 activation and modulating mitochondrial function.International journal of molecular sciences · 2013Article
- Target- and mechanism-based therapeutics for neurodegenerative diseases: strength in numbers.Journal of medicinal chemistry · 2013Review
- Article
- Potential implication of the chemical properties and bioactivity of nitrone spin traps for therapeutics.Future medicinal chemistry · 2012Review
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Oxidative stress is the main etiological factor behind the pathogenesis of various diseases including inflammation, cancer, cardiovascular and neurodegenerative disorders. Due to the spin trapping abilities and various pharmacological properties of nitrones, their application as therapeutic agent has been gaining attention. Though the antioxidant properties of the nitrones are well known, the mechanism by which they modulate the cellular defense machinery against oxidative stress is not well investigated and requires further elucidation. Here, we have investigated the mechanisms of cytoprotection of the nitrone spin traps against oxidative stress in bovine aortic endothelial cells (BAEC). Cytoprotective properties of both the cyclic nitrone 5,5-dimethyl-pyrroline N-oxide (DMPO) and linear nitrone α-phenyl N-tert-butyl nitrone (PBN) against H₂O₂-induced cytotoxicity were investigated. Preincubation of BAEC with PBN or DMPO resulted in the inhibition of H₂O₂-mediated cytotoxicity and apoptosis. Nitrone-treatment resulted in the induction and restoration of phase II antioxidant enzymes via nuclear translocation of NF-E2-related factor 2 (Nrf-2) in oxidatively-challenged cells. Furthermore, the nitrones were found to inhibit the mitochondrial depolarization and subsequent activation of caspase-3 induced by H₂O₂. Significant down-regulation of the pro-apoptotic proteins p53 and Bax, and up-regulation of the anti-apoptotic proteins Bcl-2 and p-Bad were observed when the cells were preincubated with the nitrones prior to H₂O₂-treatment. It was also observed that Nrf-2 silencing completely abolished the protective effects of nitrones. Hence, these findings suggest that nitrones confer protection to the endothelial cells against oxidative stress by modulating phase II antioxidant enzymes and subsequently inhibiting mitochondria-dependent apoptotic cascade.
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