Melanocortin-4 receptor-mediated inhibition of apoptosis in immortalized hypothalamic neurons via mitogen-activated protein kinase.
The melanocortin-4 receptor (MC4R) is a seven transmembrane member of the melanocortin receptor family. The GT1-1 cell line exhibits endogenous expression of MC4R. In this study, GT1-1 cells were used to study MC4R signaling pathways and to examine the effects of melanocortin receptor agonist NDP-MSH on apoptosis. MC4R mRNA expression was demonstrated by RT-PCR. Functional melanocortin receptor expression was implied by specific binding of NDP-MSH and cAMP production. NDP-MSH-stimulated GnRH release in a dose-dependent manner. Serum deprivation-induced apoptosis in GT1-1 cells, and the NDP-MSH inhibited this effect. The melanocortin receptor antagonist SHU9119 blocked the antiapoptotic actions of NDP-MSH, and the MAP kinase inhibitor PD98059 significantly attenuated the antiapoptotic effect. NDP-MSH-stimulated ERK1/2 phosphorylation in a dose-dependent manner. ERK1/2 phosphorylation could be abolished by SHU9119. In GT1-1 cells, melanocortin receptor activation causes ERK1/2 phosphorylation. In these cells, MC4R activation is also associated with antiapoptotic effects.
Chai
Biaoxin
B
Department of Surgery, University of Michigan, Ann Arbor, MI, USA.
Li
Ji-Yao
JY
Zhang
Weizhen
W
Newman
Erika
E
Ammori
John
J
Mulholland
Michael W
MW
D000818:Animals; D017209:Apoptosis; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D006801:Humans; D007031:Hypothalamus / Q000166:cytology / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000502:physiology*; D051379:Mice; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D044105:Receptor, Melanocortin, Type 4 / Q000502:physiology*; D015398:Signal Transduction
D044105:Receptor, Melanocortin, Type 4