International journal of molecular sciencesOct 27, 2026

Timing of UVA Light Causing Iron-Related Cell Damage in Skin Cells

Circadian Biology Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Oct 28, 2026

Abstract

Both UVA and UVB exposure reduced cell viability and increased oxidative stress markers in HaCaT keratinocytes.

UVA and UVB exposure resulted in increased reactive oxygen species, lipid peroxidation, and intracellular iron accumulation.
UVB exposure specifically reduced levels of the proteins xCT and GPX4, with a proteasome-sensitive component linked to GPX4 loss.
Transcriptomic analyses indicated complex relationships between circadian rhythms, oxidative stress, and ferroptosis-related genes in human epidermis.
Circadian genes ARNTL and NR1D1 exhibited rhythmic expression in synchronized HaCaT cells, while GPX4 and SLC7A11 did not display the same rhythmicity.
UVA-induced cytotoxic effects and oxidative stress were most pronounced at 24 hours post-exposure, indicating time-dependent susceptibility.
The compound SR8278 was able to partially preserve GPX4 levels and reduce UVA-induced oxidative damage and cell death.

Simplified

Ferroptosis contributes to ultraviolet (UV)-induced epidermal injury, but whether circadian state modifies keratinocyte susceptibility remains unclear. We integrated human epidermal transcriptomic analyses with functional experiments in HaCaT keratinocytes to compare UVA- and UVB-induced ferroptosis-associated responses and assess their temporal regulation. Both wavelengths reduced cell viability and increased reactive oxygen species, lipid peroxidation, and intracellular Fe²⁺ accumulation; ferrostatin-1 provided partial protection. UVB reduced xCT and GPX4 and showed a proteasome-sensitive component of GPX4 loss, whereas UVA predominantly reduced GPX4 without detectably altering xCT. Human epidermal transcriptomes showed heterogeneous cross-sectional associations among circadian, oxidative-stress, and ferroptosis-related genes, while longitudinal profiles revealed positive temporal coupling between NR1D1-associated signals and GPX4. In synchronized HaCaT cells, ARNTL and NR1D1 displayed 24 h rhythmicity, whereas GPX4 and SLC7A11 did not meet the prespecified rhythmicity criterion. Nevertheless, UVA-induced cytotoxicity, oxidative stress, lipid peroxidation, and GPX4 loss varied across post-synchronization time points and were greatest at 24 h. SR8278 partially preserved GPX4 abundance and attenuated UVA-induced loss of viability, reactive oxygen species accumulation, and lipid peroxidation, without significantly affecting Fe²⁺ accumulation. These findings associate circadian state with temporal variation in UVA-induced ferroptosis susceptibility and implicate the broader clock-redox system rather than rhythmic expression of individual ferroptosis effectors.

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Timing of UVA Light Causing Iron-Related Cell Damage in Skin Cells

Abstract

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