Heat-mediated reduction of apoptosis in UVB-damaged keratinocytes in vitro and in human skin ex vivo

Abstract

BackgroundUV radiation induces significant DNA damage in keratinocytes and is a known risk factor for skin carcinogenesis. However, it has been reported previously that repeated and simultaneous exposure to UV and heat stress increases the rate of cutaneous tumour formation in mice. Since constant exposure to high temperatures and UV are often experienced in the environment, the effects of exposure to UV and heat needs to be clearly addressed in human epidermal cells.MethodsIn this study, we determined the effects of repeated UVB exposure 1 kJ/m2 followed by heat (39 °C) to human keratinocytes. Normal human ex vivo skin models and primary keratinocytes (NHEK) were exposed once a day to UVB and/or heat stress for four consecutive days. Cells were then assessed for changes in proliferation, apoptosis and gene expression at 2 days post-exposure, to determine the cumulative and persistent effects of UV and/or heat in skin keratinocytes.ResultsUsing ex vivo skin models and primary keratinocytes in vitro, we showed that UVB plus heat treated keratinocytes exhibit persistent DNA damage, as observed with UVB alone. However, we found that apoptosis was significantly reduced in UVB plus heat treated samples. Immunohistochemical and whole genome transcription analysis showed that multiple UVB plus heat exposures induced inactivation of the p53-mediated stress response. Furthermore, we demonstrated that repeated exposure to UV plus heat induced SIRT1 expression and a decrease in acetylated p53 in keratinocytes, which is consistent with the significant downregulation of p53-regulated pro-apoptotic and DNA damage repair genes in these cells.ConclusionOur results suggest that UVB-induced p53-mediated cell cycle arrest and apoptosis are reduced in the presence of heat stress, leading to increased survival of DNA damaged cells. Thus, exposure to UVB and heat stress may act synergistically to allow survival of damaged cells, which could have implications for initiation skin carcinogenesis.Electronic supplementary materialThe online version of this article (doi:10.1186/s12895-016-0043-4) contains supplementary material, which is available to authorized users.

Vitamin C mitigates heat damage by reducing oxidative stress, inducing HSP expression in TM4 Sertoli cells

“…Apoptosis is commonly observed following heat stress (Calapre et al, ; Cui et al, ). Our results showed that the tested rate of apoptosis in the groups without Vc‐pretreatment increased significantly during the recovery phase.…”

Balance between Health Risks and Benefits for Outdoor Workers Exposed to Solar Radiation: An Overview on the Role of Near Infrared Radiation Alone and in Combination with Other Solar Spectral Bands

“…However, the other side of the coin should be the survival of skin cells previously mutated, for instance by exposure to solar UVR or other environmental mutagens, enabling them to proceed along the carcinogenic pathway if replicative or other promoting stimuli occur [54]. Moreover, in human keratinocytes UVB and heat stress may act synergistically by fostering the survival of mutated cells, with potential implication regarding the skin carcinogenesis pathway [55]. It is recognized that Hsp are involved in DNA repair mechanisms [56], whose increased or decreased effectiveness is, as known, related to the risk of neoplastic transformation of the cell.…”

SIRT1 activation mediates heat-induced survival of UVB damaged Keratinocytes

“…However, previous studies in our laboratory showed UVB and UVB plus heat exposures induce the same level of CPD formation. Conversely, UVB plus heat treated samples had a significantly reduced number of apoptotic keratinocytes when compared to cells treated with UVB alone [ 14 ].…”