title: Fenofibrate Increases Heme Oxygenase 1 Expression and Astrocyte Proliferation While Limits Neuronal Injury During Intracerebral Hemorrhage.
abstract: Peroxisome proliferator-activated receptors alpha (PPARα) is a therapy target in atherosclerosis and cardiovascular diseases. However, anti-inflammatory effects of PPARα in intracerebral hemorrhage (ICH) remain unknown. We investigated the anti-inflammatory effects of fenofibrate, a ligand of PPARα, in ICH rat model. We found that engagement of fenofibrate increased nissl body and astrocytes, and reduced the neuronal damage, which was observed in paraffin section of ICH rat brain. Fenofibrate also promoted the proliferation of astrocytes that were isolated from adult rat brain. Fenofibrate significantly upregulated heme oxygenase 1 (HO-1) at protein and mRNA levels in human glioblastoma LN-18 cells and rat brain astrocytes respectively, but nuclear factor kappalight- chain-enhancer of activated B cells (NFκB) was downregulated after fenofibrate treatment. Results showed that fenofibrate-induced upregulation of HO-1 expression were inhibited after LN-18 cells were transfected with 50nM small interfering RNA (siRNAs) for 48 hours to knockdown PPARα. Further studies in rat astrocytes confirmed the rescue effects of PPARα silence against fenofibrate induced upregulation of HO-1 expression. Our data indicated that fenofibrate benefits neuronal protection through increasing HO-1 expression level and decreasing NFκB expression in PPARα-dependent manner. In conclusion, PPARα and HO-1 may function as significant targets to protect the brain during ICH.
authors.affiliation: Key Laboratory of Cardiovascular Remodeling and Function Research, QiLu Hospital, Shandong University, Jinan, 250013, P.R. China|Department of Cardiology, Qingdao Municipal Hospital, Qingdao University, Qingdao, 266011,
  P.R. China
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Laboratory of Chemical Genomics, School of Chemical Biology and Biotechnology, Peking University
  Shenzhen Graduate School, Shenzhen, 518055, P.R. China
authors.forename: Min
authors.initials: M
authors.lastname: Yu
authors.affiliation: Laboratory of Chemical Genomics, School of Chemical Biology and Biotechnology, Peking University
  Shenzhen Graduate School, Shenzhen, 518055, P.R. China
authors.forename: Yue
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Department of Endocrinology, Qingdao Municipal Hospital, Qingdao University, Qingdao, 266011, P.R. China
authors.forename: Ruoping
authors.initials: R
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, Qingdao Municipal Hospital, Qingdao University, Qingdao, 266011, P.R. China
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Cardiology, Qingdao Municipal Hospital, Qingdao University, Qingdao, 266011,
  P.R. China
authors.forename: Wei
authors.initials: W
authors.lastname: Xia
authors.affiliation: Department of Cardiology, Qingdao Municipal Hospital, Qingdao University, Qingdao, 266011,
  P.R. China
authors.forename: Aili
authors.initials: A
authors.lastname: Guan
authors.affiliation: Department of Cardiology, Qingdao Municipal Hospital, Qingdao University, Qingdao, 266011,
  P.R. China
authors.forename: Conghui
authors.initials: C
authors.lastname: Xing
authors.affiliation: Laboratory of Chemical Genomics, School of Chemical Biology and Biotechnology, Peking University
  Shenzhen Graduate School, Shenzhen, 518055, P.R. China
authors.forename: Fei
authors.initials: F
authors.lastname: Lu
authors.affiliation: Key Laboratory of Cardiovascular Remodeling and Function Research, QiLu Hospital, Shandong University, Jinan, 250013, P.R. China
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Ji
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D002543:Cerebral Hemorrhage / Q000188:drug therapy*; D011345:Fenofibrate / Q000494:pharmacology*; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism*; D008297:Male; D047493:PPAR alpha / Q000187:drug effects; D034741:RNA, Small Interfering / Q000378:metabolism; D017207:Rats, Sprague-Dawley
chemical_list: D047493:PPAR alpha; D034741:RNA, Small Interfering; D051547:Heme Oxygenase-1; D011345:Fenofibrate
keywords: HO-1; NFκB; PPARα; astrocytes; fenofibrate; intracerebral hemorrhage
  ; neuronal protection; nissl body