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The B 6 ‐vitamer Pyridoxal is a Sensitizer of UVA ‐induced Genotoxic Stress in Human Primary Keratinocytes and Reconstructed Epidermis
Author(s) -
Justiniano Rebecca,
Williams Joshua D.,
Perer Jessica,
Hua Anh,
Lesson Jessica,
Park Sophia L.,
Wondrak Georg T.
Publication year - 2017
Publication title -
photochemistry and photobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.818
H-Index - 131
eISSN - 1751-1097
pISSN - 0031-8655
DOI - 10.1111/php.12720
Subject(s) - pyridoxal , chemistry , oxidative stress , human skin , dna damage , biochemistry , epidermis (zoology) , microbiology and biotechnology , endogeny , glutathione , biology , dna , enzyme , genetics , anatomy
Abstract UVA ‐driven photooxidative stress in human skin may originate from excitation of specific endogenous chromophores acting as photosensitizers. Previously, we have demonstrated that 3‐hydroxypyridine‐derived chromophores including B 6 ‐vitamers (pyridoxine, pyridoxamine and pyridoxal) are endogenous photosensitizers that enhance UVA ‐induced photooxidative stress in human skin cells. Here, we report that the B 6 ‐vitamer pyridoxal is a sensitizer of genotoxic stress in human adult primary keratinocytes ( HEK a) and reconstructed epidermis. Comparative array analysis indicated that exposure to the combined action of pyridoxal and UVA caused upregulation of heat shock ( HSPA 6 , HSPA 1A, HSPA 1L, HSPA 2 ), redox ( GSTM 3 , EGR 1 , MT 2A , HMOX 1 , SOD 1 ) and genotoxic ( GADD 45A , DDIT 3, CDKN 1A) stress response gene expression. Together with potentiation of UVA ‐induced photooxidative stress and glutathione depletion, induction of HEK a cell death occurred only in response to the combined action of pyridoxal and UVA . In addition to activational phosphorylation indicative of genotoxic stress [p53 (Ser15) and γ ‐H2 AX (Ser139)], comet analysis indicated the formation of Fpg‐sensitive oxidative DNA lesions, observable only after combined exposure to pyridoxal and UVA . In human reconstructed epidermis, pyridoxal preincubation followed by UVA exposure caused genomic oxidative base damage, procaspase 3 cleavage and TUNEL positivity, consistent with UVA ‐driven photooxidative damage that may be relevant to human skin exposed to high concentrations of B 6 ‐vitamers.