Persistent Link:
http://hdl.handle.net/10150/271940
Title:
Mechanisms of Skin Biology and Carcinogenesis
Author:
Romagnolo, Alberto
Issue Date:
2012
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 skin is a vital organ for life; whose primary function is to act as a defensive barrier. Dysfunction in the epidermal barrier of the skin is commonly observed in autosomal recessive congenital ichthyosis (ARCI). The 12R-Lipoxygenase (12R-L) and epidermis-type Lipoxygenase 3 (eLOX-3) pathway plays a key role in the process of epidermal barrier acquisition by affecting lipid metabolism, as well as protein processing. 12R-L KO mice exhibited differential expression of filaggrin, glucosyl ceramide, and ceramide markers, suggesting that they are essential in the proper formation of the epidermis. The skin disorder ARCI, provides perspective into how disruption of the normal skin physiology may contribute to pre-cancerous phenotypes like hyperplasia and dysplasia. The roles of liver kinase B1 (LKB1), adenosine monophosphate-activated protein kinase (AMPK), and human apurinic (apyrimidinic) endonuclease/redox-factor 1 (Ape1/Ref-1) are addressed to highlight some of the molecular pathways associated with ultra violet (UV)-induced skin carcinogenesis. We used UVA-340 as an energy source because it comes closest to mimicking the natural effects of sunlight exposure by containing biologically relevant amounts of UVA and UVB radiation. UVA-340 exerts carcinogenic effects, by reducing AMPK phosphorylation and the activity of its upstream kinase LKB1. Additionally, we demonstrated that UVA-340 stimulates mammalian target of rapamycin (mTOR) activation. Finally, we found that UVA-340 solar simulated light increases the abundance of Ape1/Ref-1 protein in epidermal keratinocytes. The Ape1/Ref-1 protein is involved in activating AP-1 that subsequently activates a transcriptional program associated with cellular proliferation. The natural compound resveratrol was found to inhibit AP-1 DNA binding, although at high concentrations.
Type:
text; Electronic Thesis
Degree Name:
B.S.
Degree Level:
bachelors
Degree Program:
Honors College; Molecular and Cellular Biology
Degree Grantor:
University of Arizona

Full metadata record

DC FieldValue Language
dc.language.isoenen_US
dc.titleMechanisms of Skin Biology and Carcinogenesisen_US
dc.creatorRomagnolo, Albertoen_US
dc.contributor.authorRomagnolo, Albertoen_US
dc.date.issued2012-
dc.publisherThe University of Arizona.en_US
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_US
dc.description.abstractThe skin is a vital organ for life; whose primary function is to act as a defensive barrier. Dysfunction in the epidermal barrier of the skin is commonly observed in autosomal recessive congenital ichthyosis (ARCI). The 12R-Lipoxygenase (12R-L) and epidermis-type Lipoxygenase 3 (eLOX-3) pathway plays a key role in the process of epidermal barrier acquisition by affecting lipid metabolism, as well as protein processing. 12R-L KO mice exhibited differential expression of filaggrin, glucosyl ceramide, and ceramide markers, suggesting that they are essential in the proper formation of the epidermis. The skin disorder ARCI, provides perspective into how disruption of the normal skin physiology may contribute to pre-cancerous phenotypes like hyperplasia and dysplasia. The roles of liver kinase B1 (LKB1), adenosine monophosphate-activated protein kinase (AMPK), and human apurinic (apyrimidinic) endonuclease/redox-factor 1 (Ape1/Ref-1) are addressed to highlight some of the molecular pathways associated with ultra violet (UV)-induced skin carcinogenesis. We used UVA-340 as an energy source because it comes closest to mimicking the natural effects of sunlight exposure by containing biologically relevant amounts of UVA and UVB radiation. UVA-340 exerts carcinogenic effects, by reducing AMPK phosphorylation and the activity of its upstream kinase LKB1. Additionally, we demonstrated that UVA-340 stimulates mammalian target of rapamycin (mTOR) activation. Finally, we found that UVA-340 solar simulated light increases the abundance of Ape1/Ref-1 protein in epidermal keratinocytes. The Ape1/Ref-1 protein is involved in activating AP-1 that subsequently activates a transcriptional program associated with cellular proliferation. The natural compound resveratrol was found to inhibit AP-1 DNA binding, although at high concentrations.en_US
dc.typetexten_US
dc.typeElectronic Thesisen_US
thesis.degree.nameB.S.en_US
thesis.degree.levelbachelorsen_US
thesis.degree.disciplineHonors Collegeen_US
thesis.degree.disciplineMolecular and Cellular Biologyen_US
thesis.degree.grantorUniversity of Arizonaen_US
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