title: Mesencephalic astrocyte-derived neurotrophic factor prevents neuron loss via inhibiting ischemia-induced apoptosis.
abstract: Mesencephalic astrocyte-derived neurotrophic factor (MANF) has been shown to be up-regulated under the focal cerebral ischemia and protected against ischemic injury in rats. However, the underlying mechanisms are unclear. The aim of this study was to verify the protection of MANF on the cerebral ischemic injury and further investigate the possible mechanisms. Rat focal ischemic model was established by middle cerebral artery occlusion (MCAO). The recombinant human MANF was therapeutically administrated to the ipsilateral ventricle at 2 h after MCAO. MANF decreased the number of the propidium iodide (PI)- and TUNEL-positive neural cells. Contrarily, MANF protected the NeuN-positive cells in hippocampus and cortex from death induced by ischemia. The more interesting results in this study were that MANF repressed the cleavage of caspase-3 triggered by focal cerebral ischemia. MANF also reduced the elevated levels of BIP/Grp78, phosphorylated IRE1, and splicing XBP1 induced by focal cerebral ischemia, but not affect CHOP expression. Meanwhile, focal cerebral ischemia elevated the levels of XBP1 mRNA, including unspliced XBP1 (XBP1u) and spliced XBP1 (XBP1s). However, MANF did not affect the expression of XBP1 mRNA, neither XBP1u nor XBP1s. These results suggest that MANF can prevent the neuron loss via inhibiting ischemia-induced apoptosis and regulating unfolded protein response-related genes.
authors.affiliation: School of Pharmacy, Anhui Medical University, 81 Meishan Road, Hefei, Anhui, PR China; Biopharmaceutical Research Institute, Anhui Medical University, 81 Meishan Road, Hefei, Anhui, PR China. Electronic address: 781939240@qq.com.
authors.forename: Wen
authors.initials: W
authors.lastname: Yang
authors.affiliation: School of Basic Medical Sciences, Anhui Medical University, 81 Meishan Road, Hefei, Anhui, PR China; Biopharmaceutical Research Institute, Anhui Medical University, 81 Meishan Road, Hefei, Anhui, PR China. Electronic address: jojo125520@163.com.
authors.forename: Yujun
authors.initials: Y
authors.lastname: Shen
authors.affiliation: School of Pharmacy, Anhui Medical University, 81 Meishan Road, Hefei, Anhui, PR China; Biopharmaceutical Research Institute, Anhui Medical University, 81 Meishan Road, Hefei, Anhui, PR China. Electronic address: 917879363@qq.com.
authors.forename: Ying
authors.initials: Y
authors.lastname: Chen
authors.affiliation: School of Basic Medical Sciences, Anhui Medical University, 81 Meishan Road, Hefei, Anhui, PR China; Biopharmaceutical Research Institute, Anhui Medical University, 81 Meishan Road, Hefei, Anhui, PR China. Electronic address: 526566755@qq.com.
authors.forename: Lu
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Radiology, The First Affiliated Hospital of Anhui Medical University, 218 Jixi Road, Hefei, Anhui, PR China. Electronic address: 66872156@qq.com.
authors.forename: Le
authors.initials: L
authors.lastname: Wang
authors.affiliation: School of Basic Medical Sciences, Anhui Medical University, 81 Meishan Road, Hefei, Anhui, PR China; Biopharmaceutical Research Institute, Anhui Medical University, 81 Meishan Road, Hefei, Anhui, PR China. Electronic address: histologyw@163.com.
authors.forename: Haiping
authors.initials: H
authors.lastname: Wang
authors.affiliation: School of Basic Medical Sciences, Anhui Medical University, 81 Meishan Road, Hefei, Anhui, PR China. Electronic address: 1922491779@qq.com.
authors.forename: Shengchun
authors.initials: S
authors.lastname: Xu
authors.affiliation: School of Basic Medical Sciences, Anhui Medical University, 81 Meishan Road, Hefei, Anhui, PR China; Biopharmaceutical Research Institute, Anhui Medical University, 81 Meishan Road, Hefei, Anhui, PR China. Electronic address: syf8811@gmail.com.
authors.forename: Shengyun
authors.initials: S
authors.lastname: Fang
authors.affiliation: Biopharmaceutical Research Institute, Anhui Medical University, 81 Meishan Road, Hefei, Anhui, PR China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Fu
authors.affiliation: Department of Radiology, The First Affiliated Hospital of Anhui Medical University, 218 Jixi Road, Hefei, Anhui, PR China. Electronic address: yuyongqiang@hotmail.com.
authors.forename: Yongqiang
authors.initials: Y
authors.lastname: Yu
authors.affiliation: School of Basic Medical Sciences, Anhui Medical University, 81 Meishan Road, Hefei, Anhui, PR China; Biopharmaceutical Research Institute, Anhui Medical University, 81 Meishan Road, Hefei, Anhui, PR China. Electronic address: shenyx@ustc.edu.cn.
authors.forename: Yuxian
authors.initials: Y
authors.lastname: Shen
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D020520:Brain Infarction / Q000209:etiology / Q000517:prevention & control; D053148:Caspase 3 / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D057809:HEK293 Cells; D006801:Humans; D020244:Infarction, Middle Cerebral Artery / Q000150:complications / Q000188:drug therapy* / Q000473:pathology*; D008279:Magnetic Resonance Imaging; D008297:Male; D009414:Nerve Growth Factors / Q000627:therapeutic use*; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000187:drug effects; D000071701:Regulatory Factor X Transcription Factors; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D000071717:X-Box Binding Protein 1
chemical_list: D004268:DNA-Binding Proteins; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; C546826:MANF protein, rat; D009414:Nerve Growth Factors; D018696:Neuroprotective Agents; D012333:RNA, Messenger; D000071701:Regulatory Factor X Transcription Factors; D014157:Transcription Factors; D000071717:X-Box Binding Protein 1; C000605543:XBP1 protein, human; C000605545:Xbp1 protein, rat; D053148:Caspase 3; D010751:Phosphopyruvate Hydratase
keywords: Apoptosis; Cerebral ischemia; Endoplasmic reticulum stress; Mesencephalic astrocyte-derived neurotrophic factor; Middle cerebral artery occlusion; Unfolded protein response