Melanocytes and keratinocytes have distinct and shared responses to ultraviolet radiation and arsenic

Cooper, Karen L.; Yager, Janice W.; Hudson, Laurie G.

doi:10.1016/j.toxlet.2013.11.010

Cited by 28 publications

(18 citation statements)

References 53 publications

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“…a,b). At higher UVB doses such as 30 or 40 mJ/cm 2 , however, we found that UVB had less impact on the viability of melanocytes than on keratinocytes, consistent with previous observations . While melanin produced by melanocytes is widely known to confer protection against UVR in skin cells , the molecular mechanism(s) underlying melanocyte resistance to UVB have not been clearly defined.…”

Section: Resultssupporting

confidence: 89%

Distinctive molecular responses to ultraviolet radiation between keratinocytes and melanocytes

Sun

Kim

Nakatani

et al. 2016

Experimental Dermatology

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Solar ultraviolet radiation (UVR) is the major risk factor for skin carcinogenesis. To gain new insights into the molecular pathways mediating UVR effects in the skin, we performed comprehensive transcriptomic analyses to identify shared and distinctive molecular responses to UVR between human keratinocytes and melanocytes. Keratinocytes and melanocytes were irradiated with varying doses of UVB (10, 20 and 30 mJ/cm2) then analysed by RNA-Seq at different time points post-UVB radiation (4, 24 and 72 h). Under basal conditions, keratinocytes and melanocytes expressed similar number of genes, although they each expressed a distinctive subset of genes pertaining to their specific cellular identity. Upon UVB radiation, keratinocytes displayed a clear pattern of time- and dose-dependent changes in gene expression that was different from melanocytes. The early UVB-responsive gene set (4 h post-UVR) differed significantly from delayed UVB-responsive gene sets (24 and 72 h). We also identified multiple novel UVB signature genes including PRSS23, SERPINH1, LCE3D and CNFN, which were conserved between melanocyte and keratinocyte lines from different individuals. Taken together, our findings elucidated both common and distinctive molecular features between melanocytes and keratinocytes and uncovered novel UVB signature genes that might be utilized to predict UVB photobiological effects on the skin.

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Section: Resultssupporting

confidence: 89%

Distinctive molecular responses to ultraviolet radiation between keratinocytes and melanocytes

Sun

Kim

Nakatani

et al. 2016

Experimental Dermatology

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“…Oxidative stress is thought to be involved in HQ‐induced apoptosis . The formation of reactive oxygen species (ROS) activates the caspase‐dependent pathway of apoptosis and a variety of endogenous ROS immediately activate PARP‐1 to repair DNA damage in melanocytes . To explore whether and how the PARP‐1 pathway is involved in HQ‐induced cell cycle arrest and apoptosis, we generated cell line with depletion of PARP‐1 using RNA interference (RNAi) and investigated the role of PARP‐1 in HQ‐mediated cell cycle arrest and apoptosis with a particular emphasis on the correlations between PARP‐1, caspase‐3 activation, and p53‐mediated cell death.…”

Section: Introductionmentioning

confidence: 99%

Hydroquinone induces TK6 cell growth arrest and apoptosis through PARP‐1/p53 regulatory pathway

Luo

Liang

Chen

et al. 2017

Environmental Toxicology

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Hydroquinone (HQ), one of the most important metabolites derived from benzene, induces cell cycle arrest and apoptosis. Poly(ADP-ribose) polymerase-1 (PARP-1) participates in various biological processes, including DNA repair and cell cycle regulation. To explore whether PARP-1 regulatory pathway mediated HQ-induced cell cycle arrest and apoptosis, we assessed the effect of PARP-1 suppression on induction of apoptosis analyzed by FACSCalibur flow cytometer in PARP-1 deficientTK6 cells (TK6-shPARP-1). We observed an increase in the fraction of cells in G1 phase by 7.6% and increased apoptosis by 4.5% in PARP-1-deficient TK6 cells (TK6-shPARP-1) compared to those negative control cells (TK6-shNC cells) in response to HQ treatment. Furthermore, HQ might activate the extrinsic pathways of apoptosis via up-regulation of Fas expression, followed by caspase-3 activation, apoptotic body, and sub G1 accumulation. Enhanced p53 expression was observed in TK6-shPARP-1 cells than in TK6-shNC cells after HQ treatment. In contrast, Fas expression was lower in TK6-shPARP-1 cells than in TK6-shNC cells. Therefore, we conclude that HQ may activate apoptotic signals via Fas up-regulation and p53-mediated apoptosis in TK6-shNC cells. The reduction of PARP-1 expression further intensified up-regulation of p53 in TK6-shPARP-1 cells, resulting in an increased G1→S phase cell arrest and apoptosis in TK6-shPARP-1 cells compared to TK6-shNC cells.

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“…Melanocytes are more resistant to UV induced cytotoxicity than are keratinocytes, the epidermal skin cells responsible for most non-melanoma skin cancers. This difference may explain the observation that arsenic increases the cancer incidence of non-melanoma skin cancers [86] while the relationship between arsenic and melanoma development is less clearly established [87, 88]. Since deficiencies in the removal of BPDE adducts or UV-induced photolesions by NER result in increased mutation levels, the inhibition of NER by arsenite could explain how arsenic can act as a co-carcinogen in smoking-related lung and UV-related skin cancers.…”

Section: Discussionmentioning

confidence: 99%

Inorganic arsenic inhibits the nucleotide excision repair pathway and reduces the expression of XPC

et al. 2017

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Chronic exposure to arsenic, most often through contaminated drinking water, has been linked to several types of cancer in humans, including skin and lung cancer. However, the mechanisms underlying its role in causing cancer are not well understood. There is evidence that exposure to arsenic can enhance the carcinogenicity of UV light in inducing skin cancers and may enhance the carcinogenicity of tobacco smoke in inducing lung cancers. The nucleotide excision repair (NER) pathway removes different types of DNA damage including those produced by UV light and components of tobacco smoke. The aim of the present study was to investigate the effect of sodium arsenite on the NER pathway in human lung fibroblasts (IMR-90 cells) and primary mouse keratinocytes. To measure NER, we employed a slot-blot assay to quantify the introduction and removal of UV light-induced 6-4 photoproducts (6-4 PP) and cyclobutane pyrimidine dimers (CPDs). We find a concentration-dependent inhibition of the removal of 6-4 PPs and CPDs in both cell types treated with arsenite. Treatment of both cell types with arsenite resulted in a significant reduction in the abundance of XPC, a protein that is critical for DNA damage recognition in NER. The abundance of RNA expressed from several key NER genes was also significantly reduced by treatment of IMR-90 cells with arsenite. Finally, treatment of IMR-90 cells with MG-132 abrogated the reduction in XPC protein, suggesting an involvement of the proteasome in the reduction of XPC protein produced by treatment of cells with arsenic. The inhibition of NER by arsenic may reflect one mechanism underlying the role of arsenic exposure in enhancing cigarette smoke-induced lung carcinogenesis and UV light-induced skin cancer, and it may provide some insights into the emergence of arsenic trioxide as a chemotherapeutic agent.

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Melanocytes and keratinocytes have distinct and shared responses to ultraviolet radiation and arsenic

Cited by 28 publications

References 53 publications

Distinctive molecular responses to ultraviolet radiation between keratinocytes and melanocytes

Distinctive molecular responses to ultraviolet radiation between keratinocytes and melanocytes

Hydroquinone induces TK6 cell growth arrest and apoptosis through PARP‐1/p53 regulatory pathway

Inorganic arsenic inhibits the nucleotide excision repair pathway and reduces the expression of XPC

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