The plates were placed to ice to prevent heating due to the UVA light. of DNA restoration using the comet assay showed that DNA single-strand breaks and thymine dimers were repaired quicker and more efficiently in KSCs compared with TAs. Inside a earlier work, we showed the same stem cell human population was more resistant to ionizing radiation, another carcinogenic agent. Collectively, our results combined with additional observations demonstrate that keratinocyte stem cells, which are responsible for epidermal renewal throughout existence, are equipped with an efficient arsenal against several genotoxic providers. Our future work will try to identify the factors or signaling pathways that are responsible for this PF 06465469 differential photo-sensitivity and DNA PF 06465469 restoration capacity between KSCs and TAs. Intro The epidermis is a pluristratified and differentiated epithelium composed of 90% keratinocytes. Only the basal cells of the epidermis can proliferate, which allows for its constant renewal. Along their progression to the surface, basal cells acquire different morphological and biochemical modifications, eventually leading to the with a very low cellular seeding density [10] and were described as KSCs [11]. In comparison, alpha 6high/CD71high presented characteristics similar to those shared by TAs [12,13]. The skin is definitely continually exposed to many external biological or environmental factors such as sun radiation, including UV radiation. Among the forms of radiation, UVA and UVB penetrate through the epidermis and induce DNA damage to basal cells. Because of the PF 06465469 strong absorption by DNA, UVB rays are known to generate photoproducts (cyclobutane pyrimidine dimers (CPDs), 6C4 photo-products (6-4PP) and Dewar isomers), leading to DNA mutations and cancers [14,15]. UVA rays are weakly soaked up by DNA and have been considered to be responsible for photo-ageing for years. Indeed, they generate strong oxidative stress (formation of reactive oxygen species, ROS), causing cellular damage to several macromolecules such as lipids and proteins in the dermis and epidermis [16C18]. Today, UVA rays also look like a source of DNA damage in keratinocytes, that makes this type of radiation responsible for pores and skin cancer formation [19] and has led UVA to be recognized as a class I carcinogen [20]. Indeed, by inducing ROS production, UVA rays oxidize guanine bases, forming 8-oxo-7,8-dihydroguanine (8-oxoG) from the singlet oxygen, specifically [16,21,22]. Moreover, the hydroxyl radical, ?OH, oxidizes purines and pyrimidines bases [23], but to a lesser degree [24]. The hydroxyl radical directly reacts with DNA that is situated close to its production location and induces PF 06465469 a single-strand break (SSB) by attacking 2-deoxyribose fragments [25]. UVA radiation also leads to the formation of thymine dimers [26] by two reactions as follows: direct absorption by DNA [27] and a triplet-triplet energy transfer reaction [28]. The amount of CPDs created after UVA radiation is actually higher than 8-oxoG in tradition cells [26,29] as well as in pores and skin [30]. It is notable that CPD formation in UVA-exposed pores and skin is dependent on PF 06465469 the skin phototype [31]. Finally, UVA rays do not lead to the formation of double-strand breaks (DSB) but modulate the UVB-induced photoproduct distribution by facilitating 6-4PP isomerization into Dewar isomers [26]. Both UVA and UVB induce keratinocytes response but in a different way, leading to different pores and skin response. Indeed, besides difference on penetration, sunburn and tanning induction as well as on carcinogenesis, only UVB radiation induces an increase in MC1R and CYP11B genes manifestation and in the production of CRH, ACTH and cortisol showing its implication in the local rules of neuroendocrine activities [32,33]. This neuroendocrine system appears important to coordinate local and systemic reactions to environment (via the implication of endogenous factors such Rabbit Polyclonal to MAPKAPK2 (phospho-Thr334) as melatonin, serotonin and others) as well as by its ability to reset the body homeostasis adaptation mechanisms [34]. With this context, although KSCs are responsible for epidermal renewal throughout existence, it is essential to keep up their integrity. Indeed, even if they are safeguarded by their deep location within the basal coating in their market [35] as well as their quiescent state to avoid replication mistakes, genomic instability can lead to their activation and thus to depletion, premature ageing and/or pores and skin carcinomas (examined in [36]). Because UVA and UVB radiation can reach KSCs and induce DNA damage, it seems important to specifically characterize the KSC response to UV radiation. It has previously been reported that stem cells were more resistant to numerous stressors [37C40]. In the epidermis, the same tendency was observed. Actually, an alpha6+/CD44+ cell.
