TY - JOUR
T1 - Differential signaling of glial cell line-derived neurotrophic factor and brain-derived neurotrophic factor in cultured ventral mesencephalic neurons
AU - Feng, L.
AU - Wang, C. Y.
AU - Jiang, H.
AU - Oho, C.
AU - Dugich-Djordjevic, M.
AU - Mei, Lin
AU - Lu, B.
N1 - Funding Information:
We wish to thank Dr Yi Rao, and members of the Lu lab, for helpful discussions and critical comments on the manuscript. This work was supported in part by a grant from the Shanghai Science and Technology Commission and the National Natural Science Foundation of China.
PY - 1999/6
Y1 - 1999/6
N2 - In the ventral mesencephalon, two neurotrophic factors, brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor, have been shown previously to have similar effects on the survival of dopaminergic neurons. Here, we compared the signaling mechanisms for brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor, focusing on the mitogen-associated protein kinase and the transcription factor cyclic- AMP responsive element-binding protein. Double-staining experiments indicated that many neurons co-expressed the receptors for glial cell line-derived neurotrophic factor and brain-derived neurotrophic factor, c-RET and TrkB, suggesting that they are responsive to both brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor. Although both brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor induced a rapid phosphorylation of mitogen-associated protein kinase and cyclic-AMP responsive element-binding protein, there were significant differences in the kinetics and pharmacology of the phosphorylation. The phosphorylation of mitogen-associated protein kinase by glial cell line-derived neurotrophic factor was transient; within 2 h, the level of mitogen-associated protein kinase phosphorylation returned to baseline. In contrast, the effect of brain-derived neurotrophic factor was long lasting; the mitogen-associated protein kinase remained phosphorylated for up to 4 h after brain-derived neurotrophic factor treatment. PD098059, a specific inhibitor for mitogen- associated protein kinase kinase, completely blocked the glial cell line- derived neurotrophic factor signaling through mitogen-associated protein kinase, but had no effect on brain-derived neurotrophic factor-induced mitogen-associated protein kinase phosphorylation. Both brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor induced the phosphorylation of cyclic-AMP responsive element-binding protein in the nuclei of ventral mesencephalon neurons. However, PD098059 blocked the cyclic-AMP responsive element-binding protein phosphorylation induced by glial cell line-derived neurotrophic factor, but not that by brain-derived neurotrophic factor. These results indicate that, although both brain- derived neurotrophic factor and glial cell line-derived neurotrophic factor act on ventral mesencephalon neurons, the two factors have different signaling mechanisms, which may mediate their distinctive biological functions.
AB - In the ventral mesencephalon, two neurotrophic factors, brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor, have been shown previously to have similar effects on the survival of dopaminergic neurons. Here, we compared the signaling mechanisms for brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor, focusing on the mitogen-associated protein kinase and the transcription factor cyclic- AMP responsive element-binding protein. Double-staining experiments indicated that many neurons co-expressed the receptors for glial cell line-derived neurotrophic factor and brain-derived neurotrophic factor, c-RET and TrkB, suggesting that they are responsive to both brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor. Although both brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor induced a rapid phosphorylation of mitogen-associated protein kinase and cyclic-AMP responsive element-binding protein, there were significant differences in the kinetics and pharmacology of the phosphorylation. The phosphorylation of mitogen-associated protein kinase by glial cell line-derived neurotrophic factor was transient; within 2 h, the level of mitogen-associated protein kinase phosphorylation returned to baseline. In contrast, the effect of brain-derived neurotrophic factor was long lasting; the mitogen-associated protein kinase remained phosphorylated for up to 4 h after brain-derived neurotrophic factor treatment. PD098059, a specific inhibitor for mitogen- associated protein kinase kinase, completely blocked the glial cell line- derived neurotrophic factor signaling through mitogen-associated protein kinase, but had no effect on brain-derived neurotrophic factor-induced mitogen-associated protein kinase phosphorylation. Both brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor induced the phosphorylation of cyclic-AMP responsive element-binding protein in the nuclei of ventral mesencephalon neurons. However, PD098059 blocked the cyclic-AMP responsive element-binding protein phosphorylation induced by glial cell line-derived neurotrophic factor, but not that by brain-derived neurotrophic factor. These results indicate that, although both brain- derived neurotrophic factor and glial cell line-derived neurotrophic factor act on ventral mesencephalon neurons, the two factors have different signaling mechanisms, which may mediate their distinctive biological functions.
KW - BDNF
KW - CREB
KW - GDNF
KW - MAPK
KW - Mesencephalic
KW - PD098059
UR - http://www.scopus.com/inward/record.url?scp=0033063448&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0033063448&partnerID=8YFLogxK
U2 - 10.1016/S0306-4522(99)00129-3
DO - 10.1016/S0306-4522(99)00129-3
M3 - Article
C2 - 10430490
AN - SCOPUS:0033063448
SN - 0306-4522
VL - 93
SP - 265
EP - 273
JO - Neuroscience
JF - Neuroscience
IS - 1
ER -