TY - JOUR
T1 - Molecular mechanism in activation of glutathione system by ropinirole, a selective dopamine D2 agonist
AU - Tanaka, Ken Ichi
AU - Miyazaki, Ikuko
AU - Fujita, Naoko
AU - Haque, Md Emdadul
AU - Asanuma, Masato
AU - Ogawa, Norio
N1 - Funding Information:
This work was supported in part by Grants-in-Aid for Scientific Research on Priority Areas and Scientific Research (C) and for the Encouragement of Young Scientists from the Japanese Ministry of Education, Science, Sports, and Culture, and by grants from the Research on Specific Diseases, Comprehensive Research on Aging and Health, and Research on Brain Science from the Japanese Ministry of Health and Welfare.
PY - 2001
Y1 - 2001
N2 - We have previously reported that ropinirole, a non-ergot dopamine agonist, has neuroprotective effects against 6-hydroxydopamine in mice based on in vivo antioxidant properties such as the glutathione (GSH)-activating effect. In the present study, we determined that the effects of ropinirole on the level of expression of GSH-related enzyme mRNA, these enzymes were shown to regulate GSH contents in the brain. This study focused on the mechanism of GSH enhancement by ropinirole. Striatal GSH contents were significantly increased by 7-day daily administration of ropinirole. Furthermore, the expression levels of γ-glutamylcysteine synthetase (γ-GCS), glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione S-transferase (GST) mRNA increased following daily injections of ropinirole for 7 days. In addition, ropinirole treatment for 7 days suppressed auto-oxidation in mouse striatal homogenates, in contrast to the vehicle treatment. In conclusion, ropinirole was able to suppress auto-oxidation, most probably by increasing GSH levels due to an increase of GSH synthesis. In addition, it is likely that auto-oxidation was also suppressed by the activation of GSH-regulating enzymes such as GPx, GR, and GST in the mouse striatum. Thus, our results indicate that the GSH-activating effect of ropinirole may render this dopamine agonist beneficial as a neuroprotective drug.
AB - We have previously reported that ropinirole, a non-ergot dopamine agonist, has neuroprotective effects against 6-hydroxydopamine in mice based on in vivo antioxidant properties such as the glutathione (GSH)-activating effect. In the present study, we determined that the effects of ropinirole on the level of expression of GSH-related enzyme mRNA, these enzymes were shown to regulate GSH contents in the brain. This study focused on the mechanism of GSH enhancement by ropinirole. Striatal GSH contents were significantly increased by 7-day daily administration of ropinirole. Furthermore, the expression levels of γ-glutamylcysteine synthetase (γ-GCS), glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione S-transferase (GST) mRNA increased following daily injections of ropinirole for 7 days. In addition, ropinirole treatment for 7 days suppressed auto-oxidation in mouse striatal homogenates, in contrast to the vehicle treatment. In conclusion, ropinirole was able to suppress auto-oxidation, most probably by increasing GSH levels due to an increase of GSH synthesis. In addition, it is likely that auto-oxidation was also suppressed by the activation of GSH-regulating enzymes such as GPx, GR, and GST in the mouse striatum. Thus, our results indicate that the GSH-activating effect of ropinirole may render this dopamine agonist beneficial as a neuroprotective drug.
KW - Dopamine D2 agonist
KW - Glutathione
KW - Non-ergot derivative
KW - Ropinirole
UR - http://www.scopus.com/inward/record.url?scp=0035007296&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0035007296&partnerID=8YFLogxK
U2 - 10.1023/A:1007672414239
DO - 10.1023/A:1007672414239
M3 - Article
C2 - 11358279
AN - SCOPUS:0035007296
SN - 0364-3190
VL - 26
SP - 31
EP - 36
JO - Neurochemical Research
JF - Neurochemical Research
IS - 1
M1 - 299000
ER -