The Over-Irradiation Metabolite Derivative, 24-Hydroxylumister-ol<sub>3</sub>, Reduces UV-Induced Damage in Skin

Warusavithana Gunawardena Manori De Silva; Bianca Yuko McCarthy; Jeremy Han; Chen Yang; Andrew J. A. Holland; Harvey Stern; Katie Marie Dixon; Edith Kai Yan Tang; Robert Charles Tuckey; Mark Stephen Rybchyn; Rebecca Sara Mason

doi:10.3390/metabo13070775

Metabolites (Jun 2023)

The Over-Irradiation Metabolite Derivative, 24-Hydroxylumister-ol<sub>3</sub>, Reduces UV-Induced Damage in Skin

Warusavithana Gunawardena Manori De Silva,
Bianca Yuko McCarthy,
Jeremy Han,
Chen Yang,
Andrew J. A. Holland,
Harvey Stern,
Katie Marie Dixon,
Edith Kai Yan Tang,
Robert Charles Tuckey,
Mark Stephen Rybchyn,
Rebecca Sara Mason

Affiliations

Warusavithana Gunawardena Manori De Silva: School of Medical Sciences and Bosch Institute, The University of Sydney, Sydney, NSW 2006, Australia
Bianca Yuko McCarthy: School of Medical Sciences and Bosch Institute, The University of Sydney, Sydney, NSW 2006, Australia
Jeremy Han: School of Medical Sciences and Bosch Institute, The University of Sydney, Sydney, NSW 2006, Australia
Chen Yang: School of Medical Sciences and Bosch Institute, The University of Sydney, Sydney, NSW 2006, Australia
Andrew J. A. Holland: Douglas Cohen Department of Paediatric Surgery, The Children’s Hospital at Westmead Clinical School, The Faculty of Medicine and Health, The University of Sydney, Sydney, NSW 2006, Australia
Harvey Stern: Department of Plastic and Constructive Surgery, The Royal Prince Alfred Hospital, Sydney, NSW 2050, Australia
Katie Marie Dixon: School of Medical Sciences and Bosch Institute, The University of Sydney, Sydney, NSW 2006, Australia
Edith Kai Yan Tang: School of Molecular Sciences, The University of Western Australia, Perth, WA 6009, Australia
Robert Charles Tuckey: School of Molecular Sciences, The University of Western Australia, Perth, WA 6009, Australia
Mark Stephen Rybchyn: School of Medical Sciences and Bosch Institute, The University of Sydney, Sydney, NSW 2006, Australia
Rebecca Sara Mason: School of Medical Sciences and Bosch Institute, The University of Sydney, Sydney, NSW 2006, Australia

DOI: https://doi.org/10.3390/metabo13070775
Journal volume & issue: Vol. 13, no. 7
p. 775

Abstract

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The hormonal form of vitamin D3, 1,25(OH)2D3, reduces UV-induced DNA damage. UV exposure initiates pre-vitamin D3 production in the skin, and continued UV exposure photoisomerizes pre-vitamin D3 to produce “over-irradiation products” such as lumisterol3 (L3). Cytochrome P450 side-chain cleavage enzyme (CYP11A1) in skin catalyzes the conversion of L3 to produce three main derivatives: 24-hydroxy-L3 [24(OH)L3], 22-hydroxy-L3 [22(OH)L3], and 20,22-dihydroxy-L3 [20,22(OH)L3]. The current study investigated the photoprotective properties of the major over-irradiation metabolite, 24(OH)L3, in human primary keratinocytes and human skin explants. The results indicated that treatment immediately after UV with either 24(OH)L3 or 1,25(OH)2D3 reduced UV-induced cyclobutane pyrimidine dimers and oxidative DNA damage, with similar concentration response curves in keratinocytes, although in skin explants, 1,25(OH)2D3 was more potent. The reductions in DNA damage by both compounds were, at least in part, the result of increased DNA repair through increased energy availability via increased glycolysis, as well as increased DNA damage recognition proteins in the nucleotide excision repair pathway. Reductions in UV-induced DNA photolesions by either compound occurred in the presence of lower reactive oxygen species. The results indicated that under in vitro and ex vivo conditions, 24(OH)L3 provided photoprotection against UV damage similar to that of 1,25(OH)2D3.

Published in Metabolites

ISSN: 2218-1989 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Science: Microbiology
Website: http://www.mdpi.com/journal/metabolites

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