Protective effect of bromocriptine against BH4-induced Cath.a cell death involving up-regulation of antioxidant enzymes

Previously, we suggested that tetrahydrobiopterin (BH4), an obligatory cofactor for dopamine synthesis, as an intrinsic contributor to dopaminergic neuron vulnerability. The BH4 toxicity is observed in dopamine-producing cells, including Cath.a cells, but not in non-dopaminergic cells. Furthermore,...

Full description

Saved in:
Bibliographic Details
Published in:Neuroscience letters 2009-02, Vol.451 (3), p.185-189
Main Authors: Lim, Ju Hee, Kim, Sa Suk, Boo, Doo Hyun, No, Haja, Kang, Bok Yun, Kim, Eun Mee, Hwang, Onyou, Choi, Hyun Jin
Format: Article
Language:English
Subjects:
1-Phosphatidylinositol 3-kinase
Animals
Antioxidant enzyme
Antioxidants - metabolism
Biological and medical sciences
Biopterins - analogs & derivatives
Biopterins - antagonists & inhibitors
Biopterins - toxicity
Bromocriptine
Bromocriptine - pharmacology
Bromocriptine - therapeutic use
Cath.a
Cell Death - drug effects
Cell Death - physiology
Cell Line
Cytochromes c - metabolism
Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases
Dopamine - metabolism
Dopamine Agonists - pharmacology
Enzymes - drug effects
Enzymes - metabolism
Fundamental and applied biological sciences. Psychology
L-Lactate Dehydrogenase - drug effects
L-Lactate Dehydrogenase - metabolism
Medical sciences
Mice
Neurology
Neurons - drug effects
Neurons - metabolism
Neuroprotective Agents - pharmacology
Neuroprotective Agents - therapeutic use
NF-E2-Related Factor 2 - drug effects
NF-E2-Related Factor 2 - metabolism
Nrf2
Oxidative Stress - drug effects
Oxidative Stress - physiology
Parkinson Disease - drug therapy
Parkinson Disease - metabolism
Parkinson Disease - physiopathology
Parkinson's disease
Phosphatidylinositol 3-Kinases - drug effects
Phosphatidylinositol 3-Kinases - metabolism
Receptors, Dopamine - drug effects
Receptors, Dopamine - metabolism
Signal Transduction - drug effects
Signal Transduction - physiology
Tetrahydrobiopterin (BH4)
Up-Regulation - drug effects
Up-Regulation - physiology
Vertebrates: nervous system and sense organs
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Previously, we suggested that tetrahydrobiopterin (BH4), an obligatory cofactor for dopamine synthesis, as an intrinsic contributor to dopaminergic neuron vulnerability. The BH4 toxicity is observed in dopamine-producing cells, including Cath.a cells, but not in non-dopaminergic cells. Furthermore, the dopaminergic cell death induced by BH4 is apoptotic in nature and involves oxidative stress, similar to that observed in Parkinson's disease. Accordingly, various antioxidants have been found to protect dopaminergic cells from BH4. This study was undertaken to evaluate protective effects of the dopamine receptor agonist bromocriptine on BH4-induced Cath.a cell death, because bromocriptine has been reported to be an antioxidant with a neuroprotective activity. In the presence of bromocriptine, the increase in LDH activity and mitochondrial cytochrome c release induced by BH4 were significantly abolished. This cytoprotective effect was phosphatidylinositol 3-kinase (PI3K)/Akt pathway-dependent. In addition, bromocriptine was found to up-regulate the expressions of nuclear factor-E2-related factor-2 and antioxidant enzymes including NAD(P)H quinone oxidoreductase 1. Our findings show that bromocriptine stimulates antioxidant defense mechanisms in Cath.a cells and suggest a potential use of bromocriptine as a neuroprotectant.
ISSN:0304-3940
1872-7972
DOI:10.1016/j.neulet.2008.12.056