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Galactomyces Ferment Filtrate Suppresses Melanization and Oxidative Stress in Epidermal Melanocytes

Woolridge Cooper, JàNay K, B.S.
http://orcid.org/0000-0001-6883-232X
http://rave.ohiolink.edu/etdc/view?acc_num=ucin1511799237125245

Abstract Details

2018, PhD, University of Cincinnati, Pharmacy: Pharmaceutical Sciences/Biopharmaceutics.
Epidermal melanocytes are particularly susceptible to oxidative stress and cellular cytotoxicity in comparison to the other primary skin cell types due to their normal cell function of melanin synthesis which produces reactive intermediates and oxygen species as byproducts. This vulnerability encourages the development of oxidative driven diseases such as vitiligo, a depigmenting skin disorder resulting from the dysfunction or death of melanocytes consumed by biological stress and immune targeting. Galactomyces ferment filtrate (GFF, Pitera™) is a yeast derived extract comprised of a unique blend of vitamins, minerals, small peptides, and oligosaccharides. GFF is currently used as a moisturizing agent in cosmetics and has demonstrated anti-aging, barrier enhancing, and hypopigmenting capacities in skin. GFF may have a therapeutic utility that is uniquely applicable for vitiligo patients through diminishing melanization and coupled reactive oxygen species generation, while concurrently upregulating intracellular antioxidant activity. To commence this initiative, the fundamental biological mechanisms of GFF were investigated in human pigment cell cultures. The leadoff study assessed the effect of GFF on melanization in cultured human melanoma cells and normal human melanocytes. GFF successfully inhibited melanization in both long- and short- term treatment protocols. The activity of tyrosinase, the primary melanogenic enzyme that commands biochemical melanin synthesis, was also revealed to be diminished by GFF. mRNA expression of novel ion channels and transporters associated with established modulators of cellular and organelle pH were shown to be substantially downregulated in melanocytes treated with GFF; thus, prompting the investigation of pH within the melanosome, the specialized acidic organelle that hosts the melanogenesis process. ABCC9, TRPM6, TRPV1, SLC9A4, and SLC13A1 were the gene targets selected for further experimentation. Expression of these uncharacterized ion channels and transporters were found to be reduced in GFF treated melanocytes. Three of these pore proteins also exhibited significant colocalization with melanogenic enzymes and proteins, which implies subcellular localization to melanosomes. Overall, this data demonstrated that GFF efficaciously suppressed melanization in the human pigment cell model in part by deterring tyrosine hydroxylase activity. The new working hypothesis is that GFF significantly alters the pH of the melanosome counter to optimal tyrosine hydroxylase activity via downregulation of ion transport proteins. The second study evaluated the effect of GFF in dampening oxidative stress in normal epidermal melanocytes. GFF proved cytoprotective capabilities after sustaining the cell viability in melanocytes assaulted with 4-tertiary butylphenol, an apoptotic phenolic compound. GFF also suppressed reactive oxygen species generation in cells individually challenged with 4-tertiary butylphenol and ultraviolet radiation. mRNA expression from gene regulatory elements involved in oxidative stress response were shown to be modulated after treatment; thus, instigating an examination of the Nrf2-ARE pathway. GFF positively regulated the expression of the transcription factor Nrf2 and the established downstream phase II enzyme targets HO1, NQO1, and TXNRD1 in both long and short-term treatment protocols. These results begin to explain the mechanisms of action of GFF in the suppression of melanization and oxidative stress in epidermal melanocytes.
Raymond Boissy, D.Sc. (Committee Chair)
Ana Luisa Kadekaro, Ph.D. (Committee Member)
Gary Kelm, Ph.D. (Committee Member)
R. Randall Wickett, Ph.D. (Committee Member)
Yuhang Zhang, Ph.D. (Committee Member)
161 p.
Pharmaceuticals
galactomyces ferment filtrate; melanocytes; Nrf2-ARE; pigmentation; melanosome pH; vitiligo

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Citations

  • Woolridge Cooper, J. K. (2018). Galactomyces Ferment Filtrate Suppresses Melanization and Oxidative Stress in Epidermal Melanocytes [Doctoral dissertation, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1511799237125245

    APA Style (7th edition)

  • Woolridge Cooper, JàNay. Galactomyces Ferment Filtrate Suppresses Melanization and Oxidative Stress in Epidermal Melanocytes. 2018. University of Cincinnati, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ucin1511799237125245.

    MLA Style (8th edition)

  • Woolridge Cooper, JàNay. "Galactomyces Ferment Filtrate Suppresses Melanization and Oxidative Stress in Epidermal Melanocytes." Doctoral dissertation, University of Cincinnati, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1511799237125245

    Chicago Manual of Style (17th edition)

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This open access ETD is published by University of Cincinnati and OhioLINK.