ArticleFree radical biology & medicine2014
Inducible nitric oxide synthase is key to peroxynitrite-mediated, LPS-induced protein radical formation in murine microglial BV2 cells.
Article in Free radical biology & medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 87 citations in OpenAlex.
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- Microglial activation induces nitric oxide signalling and alters protein S-nitrosylation patterns in extracellular vesicles.Journal of extracellular vesicles · 2024Article
- Amlexanox attenuates LPS-induced neuroinflammatory responses in microglial cells via inhibition of NF-κB and STAT3 signaling pathways.Scientific reports · 2024Article
- Caffeic acid alleviates cerebral ischemic injury in rats by resisting ferroptosis via Nrf2 signaling pathway.Acta pharmacologica Sinica · 2024Article
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- Integrating Network Pharmacology, Transcriptomics to Reveal Neuroprotective of Curcumin Activate PI3K / AKT Pathway in Parkinson's Disease.Drug design, development and therapy · 2024Article
- 1400 W, a selective inducible nitric oxide synthase inhibitor, mitigates early neuroinflammation and nitrooxidative stress in diisopropylfluorophosphate-induced short-term neurotoxicity rat model.Frontiers in molecular neuroscience · 2023Article
- The complex role of inflammation and gliotransmitters in Parkinson's disease.Neurobiology of disease · 2023Review
- Arginine deprivation alters microglial polarity and synergizes with radiation to eradicate non-arginine-auxotrophic glioblastoma tumors.The Journal of clinical investigation · 2022Article
- Pharmacological Modulation and (Patho)Physiological Roles of TRPM4 Channel-Part 2: TRPM4 in Health and Disease.Pharmaceuticals (Basel, Switzerland) · 2021Review
- The Emerging Scenario of the Gut-Brain Axis: The Therapeutic Actions of the New Actor Kefir against Neurodegenerative Diseases.Antioxidants (Basel, Switzerland) · 2021Review
- Nitrosative stress parameters and the level of oxidized DNA bases in patients with multiple sclerosis.Metabolic brain disease · 2021Article
- Endothelial dysfunction and body mass index: is there a role for plasma peroxynitrite?Beni-Suef University journal of basic and applied sciences · 2021Article
- Arterial stiffness is associated with oxidative stress and endothelial activation among persons with treated HIV in Zambia.Southern African journal of HIV medicine · 2021Article
- Automated Synthesis and Initial Evaluation of (4'-Amino-5',8'-difluoro-1'H-spiro[piperidine-4,2'-quinazolin]-1-yl)(4-[Molecular imaging · 2021Article
- The role of reactive oxygen species in cognitive impairment associated with sleep apnea.Experimental and therapeutic medicine · 2020Article
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Microglia are the resident immune cells in the brain. Microglial activation is characteristic of several inflammatory and neurodegenerative diseases including Alzheimer's disease, multiple sclerosis, and Parkinson's disease. Though lipopolysaccharide (LPS)-induced microglial activation in models of Parkinson's disease is well documented, the free radical-mediated protein radical formation and its underlying mechanism during LPS-induced microglial activation are not known. Here we have used immuno-spin trapping and RNA interference to investigate the role of inducible nitric oxide synthase (iNOS) in peroxynitrite-mediated protein radical formation in murine microglial BV2 cells treated with LPS. Treatment of BV2 cells with LPS resulted in morphological changes, induction of iNOS, and increased protein radical formation. Pretreatments with FeTPPS (a peroxynitrite decomposition catalyst), L-NAME (total NOS inhibitor), 1400W (iNOS inhibitor), and apocynin significantly attenuated LPS-induced protein radical formation and tyrosine nitration. Results obtained with coumarin-7-boronic acid, a highly specific probe for peroxynitrite detection, correlated with LPS-induced tyrosine nitration, which demonstrated involvement of peroxynitrite in protein radical formation. A similar degree of protection conferred by 1400W and L-NAME led us to conclude that only iNOS, and no other forms of NOS, is involved in LPS-induced peroxynitrite formation. Subsequently, siRNA for iNOS, the iNOS-specific inhibitor 1400W, the NF-κB inhibitor PDTC, and the p38 MAPK inhibitor SB202190 was used to inhibit iNOS directly or indirectly. Inhibition of iNOS precisely correlated with decreased protein radical formation in LPS-treated BV2 cells. The time course of protein radical formation also matched the time course of iNOS expression. Taken together, these results prove the role of iNOS in peroxynitrite-mediated protein radical formation in LPS-treated microglial BV2 cells.
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