Melanocortin Peptide Drug Design and Application to Feeding Behavior and Melanoma

Persistent Link:
http://hdl.handle.net/10150/579015
Title:
Melanocortin Peptide Drug Design and Application to Feeding Behavior and Melanoma
Author:
McLeod, Kaitlyn Renee
Issue Date:
2015
Publisher:
The University of Arizona.
Rights:
Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
Abstract:
The melanocortin system is comprised of 5 homeostatic G-protein coupled receptors, which regulate diverse physiological functions including skin pigmentation, erectile dysfunction, and feeding behavior. Melanocortin peptides have been applied to MC4Rs to control feeding behavior and MC1Rs to control skin pigmentation and melanoma progression. Orexin receptors, like MC4R, are expressed in the hypothalamus and affect feeding behavior, suggesting a complex relationship between orexin and melanocortin signaling. Competitive ligand binding and cAMP accumulation assays showed no stimulation of intracellular melanocortin signaling by orexin peptides, making direct cross talk between these receptors unlikely. Melanocortin peptides have also been applied to the treatment of melanoma, a cancer plagued by poor diagnosis and prognosis. Previous experimentation showed Rad-tagged NDP-α-MSH selectively binding melanoma tumors in vivo; repetitive treatments with Rho-MT-II, a non-specific melanocortin agonist, resulted in melanoma tumor shrinkage¹. In vitro, MTT colorimetric assays showed greater cell death when A375 melanoma cells were treated with an MC1R antagonist rather than an agonist. However, induction of hypotonic stress and apoptosis through simultaneous treatment with BzATP and MC1R agonist resulted an increased cell death. These results mark an important step towards developing targeted melanoma treatments.
Type:
text; Electronic Thesis
Degree Name:
B.S.
Degree Level:
bachelors
Degree Program:
Honors College; Biochemistry
Degree Grantor:
University of Arizona
Advisor:
Cai, Minying

Full metadata record

DC FieldValue Language
dc.language.isoen_USen
dc.titleMelanocortin Peptide Drug Design and Application to Feeding Behavior and Melanomaen_US
dc.creatorMcLeod, Kaitlyn Reneeen
dc.contributor.authorMcLeod, Kaitlyn Reneeen
dc.date.issued2015en
dc.publisherThe University of Arizona.en
dc.rightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.en
dc.description.abstractThe melanocortin system is comprised of 5 homeostatic G-protein coupled receptors, which regulate diverse physiological functions including skin pigmentation, erectile dysfunction, and feeding behavior. Melanocortin peptides have been applied to MC4Rs to control feeding behavior and MC1Rs to control skin pigmentation and melanoma progression. Orexin receptors, like MC4R, are expressed in the hypothalamus and affect feeding behavior, suggesting a complex relationship between orexin and melanocortin signaling. Competitive ligand binding and cAMP accumulation assays showed no stimulation of intracellular melanocortin signaling by orexin peptides, making direct cross talk between these receptors unlikely. Melanocortin peptides have also been applied to the treatment of melanoma, a cancer plagued by poor diagnosis and prognosis. Previous experimentation showed Rad-tagged NDP-α-MSH selectively binding melanoma tumors in vivo; repetitive treatments with Rho-MT-II, a non-specific melanocortin agonist, resulted in melanoma tumor shrinkage¹. In vitro, MTT colorimetric assays showed greater cell death when A375 melanoma cells were treated with an MC1R antagonist rather than an agonist. However, induction of hypotonic stress and apoptosis through simultaneous treatment with BzATP and MC1R agonist resulted an increased cell death. These results mark an important step towards developing targeted melanoma treatments.en
dc.typetexten
dc.typeElectronic Thesisen
thesis.degree.nameB.S.en
thesis.degree.levelbachelorsen
thesis.degree.disciplineHonors Collegeen
thesis.degree.disciplineBiochemistryen
thesis.degree.grantorUniversity of Arizonaen
dc.contributor.advisorCai, Minyingen
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