TitleThioredoxin Reductase 1 Modulates Pigmentation and Photobiology of Murine Melanocytes in vivo.
Publication TypeJournal Article
Year of Publication2022
AuthorsCarpenter EL, Wyant MB, Indra A, Ito S, Wakamatsu K, Merrill GF, Moos PJ, Cassidy PB, Leachman SA, Ganguli-Indra G, Indra AK
JournalJ Invest Dermatol
Date Published2022 Jul
KeywordsAnimals, Antioxidants, Melanocytes, Mice, Photobiology, Pigmentation, Thioredoxin Reductase 1, Ultraviolet Rays

Pigment-producing melanocytes overcome frequent oxidative stress in their physiological role of protecting the skin against the deleterious effects of solar UV irradiation. This is accomplished by the activity of several endogenous antioxidant systems, including the thioredoxin antioxidant system, in which thioredoxin reductase 1 (TR1) plays an important part. To determine whether TR1 contributes to the redox regulation of melanocyte homeostasis, we have generated a selective melanocytic Txnrd1-knockout mouse model (Txnrd1), which exhibits a depigmentation phenotype consisting of variable amelanotic ventral spotting and reduced pigmentation on the extremities (tail tip, ears, and paws). The antioxidant role of TR1 was further probed in the presence of acute neonatal UVB irradiation, which stimulates melanocyte activation and introduces a spike in oxidative stress in the skin microenvironment. Interestingly, we observed a significant reduction in overall melanocyte count and proliferation in the absence of TR1. Furthermore, melanocytes exhibited an elevated level of UV-induced DNA damage in the form of 8-oxo-2'-deoxyguanosine after acute UVB treatment. We also saw an engagement of compensatory antioxidant mechanisms through increased nuclear localization of transcription factor NRF2. Altogether, these data indicate that melanocytic TR1 positively regulates melanocyte homeostasis and pigmentation during development and protects against UVB-induced DNA damage and oxidative stress.

Alternate JournalJ Invest Dermatol
PubMed ID35031135
PubMed Central IDPMC10771865
Grant ListR01 ES016629 / ES / NIEHS NIH HHS / United States
T32 AT010131 / AT / NCCIH NIH HHS / United States