PMID- 18799798
OWN - NLM
STAT- MEDLINE
DCOM- 20081216
LR  - 20161124
IS  - 1521-0111 (Electronic)
IS  - 0026-895X (Linking)
VI  - 74
IP  - 6
DP  - 2008 Dec
TI  - Overexpression of heme oxygenase-1 protects dopaminergic neurons against 
      1-methyl-4-phenylpyridinium-induced neurotoxicity.
PG  - 1564-75
LID - 10.1124/mol.108.048611 [doi]
AB  - Heme oxygenase-1 (HO-1) is up-regulated in response to oxidative stress and 
      catalyzes the degradation of pro-oxidant heme to carbon monoxide (CO), iron, and 
      bilirubin. Intense HO-1 immunostaining in the Parkinsonian brain is demonstrated, 
      indicating that HO-1 may be involved in the pathogenesis of Parkinsonism. We here 
      locally injected adenovirus containing human HO-1 gene (Ad-HO-1) into rat 
      substantia nigra concomitantly with 1-methyl-4-phenylpyridinium (MPP(+)). Seven 
      days after injection of MPP(+) and Ad-HO-1, the brain was isolated for 
      immunostaining and for measurement of dopamine content and inflammatory 
      cytokines. It was found that overexpression of HO-1 significantly increased the 
      survival rate of dopaminergic neurons; reduced the production of tumor necrosis 
      factor alpha (TNF-alpha) and interleukin-1beta (IL-1beta) in substantia nigra; 
      antagonized the reduction of striatal dopamine content induced by MPP(+); and 
      also up-regulated brain-derived neurotrophic factor (BDNF) and glial cell 
      line-derived neurotrophic factor (GDNF) expression in substantia nigra. 
      Apomorphine-induced rotation after MPP(+) treatment was also inhibited by 
      Ad-HO-1. On the other hand, inhibition of HO enzymatic activity by zinc 
      protoporphyrin-IX facilitated the MPP(+)-induced rotatory behavior and enhanced 
      the reduction of dopamine content. HO-1 overexpression also protected 
      dopaminergic neurons against MPP(+)-induced neurotoxicity in midbrain neuron-glia 
      cocultures. Overexpression of HO-1 increased the expression of BDNF and GDNF in 
      astrocytes and BDNF in neurons. Our results indicate that HO-1 induction exerts 
      neuroprotection both in vitro and in vivo. Pharmacological or genetic approaches 
      targeting HO-1 may represent a promising and novel therapeutic strategy in 
      treating Parkinsonism.
FAU - Hung, Shih-Ya
AU  - Hung SY
AD  - Pharmacological Institute, College of Medicine, National Taiwan University, 
      Taipei, Taiwan.
FAU - Liou, Houng-Chi
AU  - Liou HC
FAU - Kang, Kai-Hsiang
AU  - Kang KH
FAU - Wu, Ruey-Meei
AU  - Wu RM
FAU - Wen, Chun-Chiang
AU  - Wen CC
FAU - Fu, Wen-Mei
AU  - Fu WM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080917
PL  - United States
TA  - Mol Pharmacol
JT  - Molecular pharmacology
JID - 0035623
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Glial Cell Line-Derived Neurotrophic Factor)
RN  - 0 (Interleukin-1beta)
RN  - 0 (RNA, Messenger)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 1.14.14.18 (Heme Oxygenase-1)
RN  - R865A5OY8J (1-Methyl-4-phenylpyridinium)
RN  - VTD58H1Z2X (Dopamine)
SB  - IM
MH  - *1-Methyl-4-phenylpyridinium
MH  - Adenoviridae/genetics
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/biosynthesis/genetics
MH  - Cell Death
MH  - Cells, Cultured
MH  - Coculture Techniques
MH  - Dopamine/*metabolism
MH  - Enzyme Induction
MH  - Glial Cell Line-Derived Neurotrophic Factor/biosynthesis/genetics
MH  - Heme Oxygenase-1/*biosynthesis/genetics
MH  - Humans
MH  - Interleukin-1beta/metabolism
MH  - Neuroglia/pathology
MH  - Neurons/*pathology
MH  - Parkinson Disease, Secondary/chemically induced/enzymology/*pathology
MH  - RNA, Messenger/biosynthesis
MH  - Rats
MH  - Rats, Wistar
MH  - Tumor Necrosis Factor-alpha/metabolism
EDAT- 2008/09/19 09:00
MHDA- 2008/12/17 09:00
CRDT- 2008/09/19 09:00
PHST- 2008/09/19 09:00 [pubmed]
PHST- 2008/12/17 09:00 [medline]
PHST- 2008/09/19 09:00 [entrez]
AID - mol.108.048611 [pii]
AID - 10.1124/mol.108.048611 [doi]
PST - ppublish
SO  - Mol Pharmacol. 2008 Dec;74(6):1564-75. doi: 10.1124/mol.108.048611. Epub 2008 Sep 
      17.