title: Heme oxygenase 1 plays role of neuron-protection by regulating Nrf2-ARE signaling post intracerebral hemorrhage.
abstract: The NF-E2 related factor 2 (Nrf2) could be activated in intracerebral hemorrhage (ICH), and trigger the expression of ARE regulated heme oxygenase 1 (HO-1) subsequently. This study aims to explore neuroprotection of HO-1 protein in regulating the Nrf2-ARE signaling pathway in ICH. In this study, the femoral artery injection method was used to establish the ICH model. The zinc porphyrin-9 (ZPP-IX) was used to inhibit the HO-1 expression in ICH rats. The ICH rats were randomly divided into 3 groups, ICH group, ZPP-IX (10 mg/kg) + ICH group and DMSO (10 mg/kg) + ICH group. Neurological scores were evaluated for the 3 groups. Double immunofluorescence staining method was employed to observe the co-expression of HO-1, Nrf2, NF-κB and TNF-α and CD11b in glia cells. Western blot and RT-PCR assay were used to detect the total Nrf2, binding Nrf2, HO-1, NF-κB and TNF-α expression. The results indicated that ZPP-IX could aggravate the neurological dyafunstions of ICH rats. The HO-1 level in ZPP-IX group was significantly decreased compared to the ICH group (P < 0.05). The binding-Nrf2 protein was significantly increased in ZPP-IX group compared to ICH group (P < 0.05). The NF-κB and TNF-α level were significantly increased in ZPP-IX group compared to ICH group (P < 0.05). The ZPP-IX significantly inhibited the HO-1 and Nrf2, and enhanced NF-κB and TNF-α co-expressing with the CD11b compared to the ICH group (P < 0.05). In conclusion, HO-1 protein regulates the Nrf2-ARE pathway in ICH model by inhibiting the Nrf2 entering nucleus and activating the NF-κB and TNF-α expression.
authors.affiliation: Department of Neurology, The Second Affiliated Hospital of Nanchang University Nanchang, China ; Department of Neurology, Affiliated Hospital of Jiujiang University Jiujiang, China.
authors.forename: Xiao-Ping
authors.initials: XP
authors.lastname: Yin
authors.affiliation: Department of Neurology, The Sixth Hospital of Wuhan Wuhan, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Wu
authors.affiliation: Department of Neurology, The Second Affiliated Hospital of Nanchang University Nanchang, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Neurology, Affiliated Hospital of Jiujiang University Jiujiang, China.
authors.forename: Zhi-Ying
authors.initials: ZY
authors.lastname: Chen
authors.affiliation: Department of Neurology, Affiliated Hospital of Jiujiang University Jiujiang, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Bao
authors.affiliation: Department of Neurology, The Second Affiliated Hospital of Nanchang University Nanchang, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Xie
mesh_terms: D000818:Animals; D002265:Carboxylic Ester Hydrolases / Q000378:metabolism*; D002543:Cerebral Hemorrhage / Q000378:metabolism* / Q000473:pathology; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D051267:NF-E2-Related Factor 2; D016328:NF-kappa B; C495637:Nfe2l2 protein, rat; D014409:Tumor Necrosis Factor-alpha; D051547:Heme Oxygenase-1; D002265:Carboxylic Ester Hydrolases; C019734:arylesterase
keywords: Intracerebral hemorrhage; Nrf2-ARE signaling; heme oxygenase 1; zinc porphyrin-9