The DOI matches its Crossref record; 9 of the 9 references it cites were found in a registry or an index.
The Microglial α7-Acetylcholine Nicotinic Receptor Is a Key Element in Promoting Neuroprotection by Inducing Heme Oxygenase-1 via Nuclear Factor Erythroid-2-Related Factor 2
Open accessAbstract
AIMS: We asked whether the neuroprotective effect of cholinergic microglial stimulation during an ischemic event acts via a mechanism involving the activation of nuclear factor erythroid-2-related factor 2 (Nrf2) and/or the expression of its target cytoprotective gene, heme oxygenase-1 (HO-1). Specifically, the protective effect of the pharmacologic alpha-7 nicotinic acetylcholine receptor (α7 nAChR) agonist PNU282987 was analyzed in organotypic hippocampal cultures (OHCs) subjected to oxygen and glucose deprivation (OGD) in vitro as well as in photothrombotic stroke in vivo. RESULTS: OHCs exposed to OGD followed by reoxygenation elicited cell death, measured by propidium iodide and 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide staining. Activation of α7 nAChR by PNU282987, after OGD, reduced cell death, reactive oxygen species production, and tumor necrosis factor release. This was associated with induction of HO-1 expression, an effect reversed by α-bungarotoxin and by tin-protoporphyrin IX. The protective effect of PNU282987 was lost in microglial-depleted OHCs as well as in OHCs from Nrf2-deficient-versus-wild-type mice, an effect associated with suppression of HO-1 expression in microglia. Administration of PNU282987 1 h after induction of photothrombotic stroke in vivo reduced the infarct size and improved motor skills in Hmox1(lox/lox) mice that express normal levels of HO-1, but not in LysM(Cre)Hmox1(Δ/Δ) in which HO-1 expression is inhibited in myeloid cells, including the microglia. INNOVATION: This study suggests the participation of the microglial α7 nAChR in the brain cholinergic anti-inflammatory pathway. CONCLUSION: Activation of the α7 nAChR/Nrf2/HO-1 axis in microglia regulates neuroinflammation and oxidative stress, affording neuroprotection under brain ischemic conditions.
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Cites
Microglia-mediated neurotoxicity: uncovering the molecular mechanisms
Block, M. L., Zecca, L., & Hong, J.-S. (2007) · Nature Reviews Neuroscience · doi:10.1038/nrn2038 · Cited by 4,110
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Nicotinic acetylcholine receptor α7 subunit is an essential regulator of inflammation
Wang, H., Yu, M., Ochani, M., Amella, C. A., Tanovic, M., Susarla, S., Li, J. H., Wang, H., Yang, H., Ulloa, L., et al. (2003) · Nature · doi:10.1038/nature01339 · Cited by 3,228
Mechanisms of Cell Protection by Heme Oxygenase-1
Gozzelino, R., Jeney, V., & Soares, M. P. (2010) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pharmtox.010909.105600 · Cited by 1,241
Self-citationCarbon Monoxide Generated by Heme Oxygenase 1 Suppresses Endothelial Cell Apoptosis
Brouard, S., Otterbein, L. E., Anrather, J., Tobiasch, E., Bach, F. H., Choi, A. M. K., & Soares, M. P. (2000) · The Journal of Experimental Medicine · doi:10.1084/jem.192.7.1015 · Cited by 984
Self-citationHeme oxygenase-1: from biology to therapeutic potential
Soares, M. P., & Bach, F. H. (2009) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2008.12.004 · Cited by 257
Self-citationTaillé, C., El-Benna, J., Lanone, S., Boczkowski, J., & Motterlini, R. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m503512200 · Cited by 246 · cited 1×
“Heme degradation by HO-1 in microglia generates CO (33), a gasotransmitter that can inhibit NADPH oxidase (55), the main enzyme responsible for microglial ROS production (4) promoting microglial activation during neuroinflammation (7).”
Stevens, T. R., Krueger, S. R., Fitzsimonds, R. M., & Picciotto, M. R. (2003) · The Journal of Neuroscience · doi:10.1523/jneurosci.23-31-10093.2003 · Cited by 119
Immunoregulatory effects of HO-1: how does it work?
Soares, M. P., Marguti, I., Cunha, A., & Larsen, R. (2009) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2009.05.008 · Cited by 97
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Neuroinflammation: friend and foe for ischemic stroke
Jayaraj, R. L., Azimullah, S., Beiram, R., Jalal, F. Y., & Rosenberg, G. A. (2019) · Journal of Neuroinflammation · doi:10.1186/s12974-019-1516-2 · Cited by 1,428
Electrophilic properties of itaconate and derivatives regulate the IκBζ–ATF3 inflammatory axis
Bambouskova, M., Gorvel, L., Lampropoulou, V., Sergushichev, A., Loginicheva, E., Johnson, K., Korenfeld, D., Mathyer, M. E., Kim, H., Huang, L.-H., et al. (2018) · Nature · doi:10.1038/s41586-018-0052-z · Cited by 713
Self-citationThe biphasic function of microglia in ischemic stroke
Ma, Y., Wang, J., Wang, Y., & Yang, G.-Y. (2017) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2016.01.005 · Cited by 655
Rada, P., Rojo, A. I., Evrard-Todeschi, N., Innamorato, N. G., Cotte, A., Jaworski, T., Tobón-Velasco, J. C., Devijver, H., García-Mayoral, M. F., Van Leuven, F., et al. (2012) · Molecular and Cellular Biology · doi:10.1128/mcb.00180-12 · Cited by 474
Cholinergic modulation of the immune system presents new approaches for treating inflammation
Hoover, D. B. (2017) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2017.05.002 · Cited by 300
Metadata
- Authors
- Parada, E., Egea, J., Buendia, I., Negredo, P., Cunha, A. C., Cardoso, S., Soares, M. P., & López, M. G.
- Venue
- Antioxidants & Redox Signaling
- Publisher
- SAGE Publications
- Published
- 2013-10-10
- Volume
- 19
- Issue
- 11
- Pages
- 1135-1148
- ISSN
- 1523-0864 (ISSN-L)
- 1557-7716
- OpenAlex
- W2015928690
- Cited by
- 198
- References
- 9
- FWCI
- 7.71
- Type
- journal article
- Language
- en
- Open access
- green
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- Parada, E., Egea, J., Buendia, I., Negredo, P., Cunha, A. C., Cardoso, S., Soares, M. P., & López, M. G. (2013). The Microglial α7-Acetylcholine Nicotinic Receptor Is a Key Element in Promoting Neuroprotection by Inducing Heme Oxygenase-1 via Nuclear Factor Erythroid-2-Related Factor 2. Antioxidants & Redox Signaling. https://doi.org/10.1089/ars.2012.4671
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