PMID- 28382863
OWN - NLM
STAT- MEDLINE
DCOM- 20171027
LR  - 20190327
IS  - 1875-5739 (Electronic)
IS  - 1567-2026 (Linking)
VI  - 14
IP  - 1
DP  - 2017
TI  - Fenofibrate Increases Heme Oxygenase 1 Expression and Astrocyte Proliferation 
      While Limits Neuronal Injury During Intracerebral Hemorrhage.
PG  - 11-18
LID - 10.2174/1567202613666161014161943 [doi]
AB  - Peroxisome proliferator-activated receptors alpha (PPARalpha) is a therapy target in 
      atherosclerosis and cardiovascular diseases. However, anti-inflammatory effects 
      of PPARalpha in intracerebral hemorrhage (ICH) remain unknown. We investigated the 
      anti-inflammatory effects of fenofibrate, a ligand of PPARalpha, 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 (NFkappaB) 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 PPARalpha. Further studies in rat 
      astrocytes confirmed the rescue effects of PPARalpha 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 NFkappaB expression in PPARalpha-dependent manner. In conclusion, PPARalpha and 
      HO-1 may function as significant targets to protect the brain during ICH.
CI  - Copyright(c) Bentham Science Publishers; For any queries, please email at 
      epub@benthamscience.org.
FAU - Wang, Yan
AU  - Wang Y
AD  - Key Laboratory of Cardiovascular Remodeling and Function Research, QiLu Hospital, 
      Shandong University, Jinan, 250013, P.R. China
AD  - Department of Cardiology, Qingdao Municipal Hospital, Qingdao University, 
      Qingdao, 266011, P.R. China
FAU - Yu, Min
AU  - Yu M
AD  - Laboratory of Chemical Genomics, School of Chemical Biology and Biotechnology, 
      Peking University Shenzhen Graduate School, Shenzhen, 518055, P.R. China
FAU - Ma, Yue
AU  - Ma Y
AD  - Laboratory of Chemical Genomics, School of Chemical Biology and Biotechnology, 
      Peking University Shenzhen Graduate School, Shenzhen, 518055, P.R. China
FAU - Wang, Ruoping
AU  - Wang R
AD  - Department of Endocrinology, Qingdao Municipal Hospital, Qingdao University, 
      Qingdao, 266011, P.R. China
FAU - Liu, Wei
AU  - Liu W
AD  - Department of Neurosurgery, Qingdao Municipal Hospital, Qingdao University, 
      Qingdao, 266011, P.R. China
FAU - Xia, Wei
AU  - Xia W
AD  - Department of Cardiology, Qingdao Municipal Hospital, Qingdao University, 
      Qingdao, 266011, P.R. China
FAU - Guan, Aili
AU  - Guan A
AD  - Department of Cardiology, Qingdao Municipal Hospital, Qingdao University, 
      Qingdao, 266011, P.R. China
FAU - Xing, Conghui
AU  - Xing C
AD  - Department of Cardiology, Qingdao Municipal Hospital, Qingdao University, 
      Qingdao, 266011, P.R. China
FAU - Lu, Fei
AU  - Lu F
AD  - Laboratory of Chemical Genomics, School of Chemical Biology and Biotechnology, 
      Peking University Shenzhen Graduate School, Shenzhen, 518055, P.R. China
FAU - Ji, Xiaoping
AU  - Ji X
AD  - Key Laboratory of Cardiovascular Remodeling and Function Research, QiLu Hospital, 
      Shandong University, Jinan, 250013, P.R. China
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United Arab Emirates
TA  - Curr Neurovasc Res
JT  - Current neurovascular research
JID - 101208439
RN  - 0 (PPAR alpha)
RN  - 0 (RNA, Small Interfering)
RN  - EC 1.14.14.18 (Heme Oxygenase-1)
RN  - U202363UOS (Fenofibrate)
SB  - IM
MH  - Animals
MH  - Astrocytes/cytology/*drug effects/metabolism
MH  - Brain/*drug effects/metabolism
MH  - Cell Proliferation/*drug effects
MH  - Cells, Cultured
MH  - Cerebral Hemorrhage/*drug therapy
MH  - Fenofibrate/*pharmacology
MH  - Heme Oxygenase-1/genetics/*metabolism
MH  - Male
MH  - PPAR alpha/drug effects
MH  - RNA, Small Interfering/metabolism
MH  - Rats, Sprague-Dawley
OTO - NOTNLM
OT  - HO-1
OT  - NFkappaB
OT  - PPARalpha
OT  - astrocytes
OT  - fenofibrate
OT  - intracerebral hemorrhage
OT  - neuronal protection
OT  - nissl body
EDAT- 2017/04/07 06:00
MHDA- 2017/10/28 06:00
CRDT- 2017/04/07 06:00
PHST- 2016/08/28 00:00 [received]
PHST- 2016/10/04 00:00 [revised]
PHST- 2016/10/05 00:00 [accepted]
PHST- 2017/04/07 06:00 [entrez]
PHST- 2017/04/07 06:00 [pubmed]
PHST- 2017/10/28 06:00 [medline]
AID - CNR-EPUB-78962 [pii]
AID - 10.2174/1567202613666161014161943 [doi]
PST - ppublish
SO  - Curr Neurovasc Res. 2017;14(1):11-18. doi: 10.2174/1567202613666161014161943.