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Pharmacologic induction of the melan...

Amaro-Ortiz, Alexandra.

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Pharmacologic induction of the melanocotin 1 receptor (MC1R) pathway provides protection against sunburn and enhances expression of antioxidant enzymes in the skin.

Record Type:	Electronic resources : Monograph/item
Title/Author:	Pharmacologic induction of the melanocotin 1 receptor (MC1R) pathway provides protection against sunburn and enhances expression of antioxidant enzymes in the skin./
Author:	Amaro-Ortiz, Alexandra.
Description:	136 p.
Notes:	Source: Dissertation Abstracts International, Volume: 76-10(E), Section: B.
Contained By:	Dissertation Abstracts International76-10B(E).
Subject:	Toxicology. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3707927
ISBN:	9781321828191

Pharmacologic induction of the melanocotin 1 receptor (MC1R) pathway provides protection against sunburn and enhances expression of antioxidant enzymes in the skin.
Amaro-Ortiz, Alexandra.

Pharmacologic induction of the melanocotin 1 receptor (MC1R) pathway provides protection against sunburn and enhances expression of antioxidant enzymes in the skin. - 136 p.

Source: Dissertation Abstracts International, Volume: 76-10(E), Section: B.

Thesis (Ph.D.)--University of Kentucky, 2015.

This item must not be sold to any third party vendors.

The inability to tan properly after sun exposure strongly correlates with increased incidence of skin cancer. The melanocortin 1 receptor (MC1R) is a transmembrane Gscoupled cell surface receptor found on epidermal melanocytes that transmits pro-survival and pro-differentiation signals mediated by the second messenger cAMP. Humans carrying loss-of-function polymorphisms in MC1R signaling exhibit higher incidences of skin cancers including melanoma.

ISBN: 9781321828191Subjects--Topical Terms:

556884
Toxicology.

Pharmacologic induction of the melanocotin 1 receptor (MC1R) pathway provides protection against sunburn and enhances expression of antioxidant enzymes in the skin.
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020 $a 9781321828191
035 $a (MiAaPQ)AAI3707927
035 $a AAI3707927
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100 1 $a Amaro-Ortiz, Alexandra. $3 3181363
245 1 0 $a Pharmacologic induction of the melanocotin 1 receptor (MC1R) pathway provides protection against sunburn and enhances expression of antioxidant enzymes in the skin.
300 $a 136 p.
500 $a Source: Dissertation Abstracts International, Volume: 76-10(E), Section: B.
500 $a Adviser: John A. D'Orazio.
502 $a Thesis (Ph.D.)--University of Kentucky, 2015.
506 $a This item must not be sold to any third party vendors.
520 $a The inability to tan properly after sun exposure strongly correlates with increased incidence of skin cancer. The melanocortin 1 receptor (MC1R) is a transmembrane Gscoupled cell surface receptor found on epidermal melanocytes that transmits pro-survival and pro-differentiation signals mediated by the second messenger cAMP. Humans carrying loss-of-function polymorphisms in MC1R signaling exhibit higher incidences of skin cancers including melanoma.
520 $a This study focused on the physiologic effects of topical application of forskolin, an adenylate cyclase activator, in extension (Mc1re/e) K14-SCF animals, which model the fairskinned UV-sensitive human. Twice daily application of the drug promoted accelerated pigmentation, increased skin darkening due to epidermal deposition of melanin pigment, and induced epidermal melanin, which protected the skin against UV injury as judged by "minimal erythematous dose" (MED). Moreover, MC1R signaling regulated the expression of antioxidant enzymes at the transcriptional level. The human melanoma cell line A375, known to harbor a loss-of-function signaling mutation in MC1R, was used to determine effects of cAMP stimulation on the expression of antioxidant enzymes. We observed increases in expression of genes that control the biosynthesis and regulation of glutathione including the transcription factor nuclear factor (erythroid-derived 2)-like 2 (Nrf2), glutathione peroxidase, GPX, and glutathione reductase GSR. In addition, there is an increase in manganese superoxide dismutase (MnSOD) at the protein level. There was accumulation of MnSOD in the mitochondria after pharmacologic induction of cAMP with forskolin. Addition of the oxidative agent H2O2 enhanced the expression of MnSOD at the protein level as early as one hour after MC1R stimulation. Oxygen consumption rate on mitochondria was measured using Seahorse analysis; pharmacologic activation of MC1R/cAMP signaling did not affect mitochondrial metabolism. In addition, topical application of a crude extract of Solidago inhibited UV-induced inflammation in K14-SCF mice. Several UV-induced cytokines, including TNF-alpha, were down-regulated at the transcriptional level after topical application of Solidago extract.
520 $a Together, these results indicate that MC1R signaling protects melanocytes from UV damage by regulating antioxidant enzyme expression and suggest that pharmacologic cAMP induction may be a useful preventive mechanism against UV-mediated skin sunburn and oxidative injury.
590 $a School code: 0102.
650 4 $a Toxicology. $3 556884
650 4 $a Molecular biology. $3 517296
650 4 $a Pharmacology. $3 634543
690 $a 0383
690 $a 0307
690 $a 0419
710 2 $a University of Kentucky. $b Toxicology and Cancer Biology. $3 3181364
773 0 $t Dissertation Abstracts International $g 76-10B(E).
790 $a 0102
791 $a Ph.D.
792 $a 2015
793 $a English
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3707927