{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T22:47:36Z","timestamp":1784242056983,"version":"3.55.0"},"reference-count":21,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2023,8,30]],"date-time":"2023-08-30T00:00:00Z","timestamp":1693353600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Environmental Toxicology"],"published-print":{"date-parts":[[2023,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>BRCA1 associated protein (BRAP) participates in the regulation of myocardial infarction and atherosclerosis. But the function of BRAP in cerebral ischemia\u2013reperfusion (CIR) injury has not been elucidated yet.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>BRAP expression in PC12 cells in response to oxygen\u2013glucose deprivation\/reoxygenation (OGD\/R) treatment was examined with Western blot assay. PC12 cells underwent OGD\/R\u2010treatment and were subsequently transfected with pcDNA\u2010BRAP or sh\u2010BRAP, followed by determination of viability, lactate dehydrogenase (LDH) production, apoptosis, inflammatory cytokine secretion, and oxidative stress marker protein levels. Paraoxonase 1 (PON1) promoter methylation was evaluated with methylation\u2010specific PCR assay. the effect of BRAP\/PON1 axis on CIR injury was investigated by rescue experiments. Additionally, sh\u2010BRAP was injected into a middle cerebral artery occlusion (MCAO) rat model, and the changes of neurological damage were evaluated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>BRAP overexpression exacerbated OGD\/R\u2010induced viability reduction, LDH production, apoptosis, inflammatory cytokine secretion and oxidative stress in PC12 neuronal cells. In contrast, BRAP silencing showed the opposite results. Mechanistically, BRAP reduced PON1 expression by promoting DNA methyl transferase1 (DNMT1)\u2010mediated PON1 promoter methylation. PON1 silencing reversed BRAP\u2010mediated neuroprotection. Additionally, BRAP silencing alleviated CIR\u2010induced neurological damage in MCAO rats.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>BRAP silencing suppressed OGD\/R\u2010induced neuronal apoptosis, inflammation, and oxidative stress, and alleviated CIR\u2010induced neurological damage in MCAO rats through facilitating PON1 expression.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/tox.23899","type":"journal-article","created":{"date-parts":[[2023,8,30]],"date-time":"2023-08-30T13:44:50Z","timestamp":1693403090000},"page":"2645-2655","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["<scp>BRAP<\/scp>\n                    silencing protects against neuronal inflammation, oxidative stress and apoptosis in cerebral ischemia\u2013reperfusion injury by promoting\n                    <scp>PON1<\/scp>\n                    expression"],"prefix":"10.1002","volume":"38","author":[{"given":"Tao","family":"Kang","sequence":"first","affiliation":[{"name":"Department of Neurology Shaanxi Provincial People's Hospital  Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Qin","sequence":"additional","affiliation":[{"name":"Department of Neurology Shaanxi Provincial People's Hospital  Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Lei","sequence":"additional","affiliation":[{"name":"Department of Neurology Shaanxi Provincial People's Hospital  Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Neurology Shaanxi Provincial People's Hospital  Xi'an 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