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, 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.
Lim
Ju Hee
JH
Chonnam National University, Gwangju 500-757, South Korea.
Kim
Sa Suk
SS
Boo
Doo Hyun
DH
No
Haja
H
Kang
Bok Yun
BY
Kim
Eun Mee
EM
Hwang
Onyou
O
Choi
Hyun Jin
HJ
D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D001708:Biopterins / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000633:toxicity; D001971:Bromocriptine / Q000494:pharmacology* / Q000627:therapeutic use; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D045304:Cytochromes c / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D018491:Dopamine Agonists / Q000494:pharmacology; D004798:Enzymes / Q000187:drug effects / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D051267:NF-E2-Related Factor 2 / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D010300:Parkinson Disease / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D019869:Phosphatidylinositol 3-Kinases / Q000187:drug effects / Q000378:metabolism; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D000975:Antioxidants; D018491:Dopamine Agonists; D004798:Enzymes; D051267:NF-E2-Related Factor 2; D018696:Neuroprotective Agents; D011954:Receptors, Dopamine; D001708:Biopterins; D001971:Bromocriptine; D045304:Cytochromes c; D007770:L-Lactate Dehydrogenase; D019869:Phosphatidylinositol 3-Kinases; C003402:sapropterin; D004298:Dopamine