Skin presenting a higher level of caspase‐14 is better protected from UVB irradiation according to <i>in vitro</i> and <i>in vivo</i> studies

Bergeron, L.; Gondran, C.; Oberto, G.; Garcia, N.; Botto, J.; Cucumel, K.; Farra, Claude Dal; Domloge, N.

doi:10.1111/j.1473-2165.2012.00615.x

Cited by 12 publications

(9 citation statements)

References 20 publications

(39 reference statements)

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“…Caspase 14 is activated in the apical layers where the cells also express the cofactor of caspase 14 filaggrin and cleavage of pro-filaggrin to filaggrin is associated with activated caspase 14 [12,13]. The functions of caspase 14 and filaggrin are the protection against UVB light and these proteins are also involved in the hydration status of the skin [12,[14][15][16][17][18]. Caspase 14 is involved in degenerative and neoplastic diseases.…”

Section: Introductionmentioning

confidence: 99%

Expression of Caspase 14 and Filaggrin in Oral Squamous Carcinoma

Scharenberg

Eckardt

Tiede

et al. 2013

Head and Neck Pathol

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Caspase 14 is one of the latter discovered members of the caspase enzyme family and, although sharing sequence homologies with the other caspases, it is not involved in apoptosis. Together with its co-factor filaggrin, it plays an important role in skin barrier formation. It is already known that caspase 14 proteins are reduced during neoplastic dedifferentiation in cervical intraepithelial neoplasms and in invasive cervical carcinomas. Oral squamous carcinoma tissues have not been systematically evaluated for caspase 14 expression yet. Formalin-fixed and paraffin-embedded samples from oral squamous carcinomas (n = 36 tumours from 34 patients), metastases (n = 15) and controls (leukoplakia, n = 10) were analysed by immunohistochemistry. In carcinomas, human papilloma virus (HPV) infection was tested by PCR. Here we demonstrate that, in oral epithelia, caspase 14 is expressed mainly by cells of the intermediate and superficial cell layers while filaggrin is expressed only in keratinising foci in leukoplakia. Caspase 14 and filaggrin are co-localised. In invasive oral carcinomas, reduced expression of caspase 14 was detectable in 47 % of tumours but was not associated with keratinisation, tumour differentiation or HPV infection. Filaggrin was detectable in a subfraction of tumours (56 %) and was restricted to keratinising areas of the carcinomas. In summary, in contrast to cervical carcinomas, partial loss of caspase 14 is not associated with dedifferentiation in neoplastic lesions of the oral mucosa or HPV infection.

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Section: Introductionmentioning

confidence: 99%

Expression of Caspase 14 and Filaggrin in Oral Squamous Carcinoma

Scharenberg

Eckardt

Tiede

et al. 2013

Head and Neck Pathol

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“…First, to quantitatively evaluate skin barrier function, we measured Transepidermal Water Loss (TEWL). This non-invasive metric measures the rate of water evaporation from the skin surface, with increasing TEWL values correlating to increasing compromise of the skin’s barrier function (Bergeron et al, 2012; Brand and Jendrzejewski, 2008). Consistent with clinical appearance, irradiated control groups demonstrated severe compromise in skin barrier function.…”

Section: Resultsmentioning

confidence: 99%

A Topical Mitochondria-Targeted Redox-Cycling Nitroxide Mitigates Oxidative Stress-Induced Skin Damage

Brand

Epperly

Stottlemyer

et al. 2017

Journal of Investigative Dermatology

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Skin is the largest human organ and provides a first line of defense that includes physical, chemical, and immune mechanisms to combat environmental stress. Radiation is a prevalent environmental stressor. Radiation induced skin damage ranges from photoaging and cutaneous carcinogenesis from UV exposure, to treatment-limiting radiation dermatitis associated with radiotherapy, to cutaneous radiation syndrome, a frequently fatal consequence of exposures from nuclear accidents. The major mechanism of skin injury common to these exposures is radiation induced oxidative stress. Efforts to prevent or mitigate radiation damage have included development of antioxidants capable of reducing reactive oxygen species (ROS). Mitochondria are particularly susceptible to oxidative stress, and mitochondrial dependent apoptosis plays a major role in radiation induced tissue damage. We reasoned that targeting a redox cycling nitroxide to mitochondria could prevent ROS accumulation, limiting downstream oxidative damage and preserving mitochondrial function. Here we show that in both mouse and human skin, topical application of a mitochondrial targeted antioxidant prevents and mitigates radiation induced skin damage characterized by clinical dermatitis, loss of barrier function, inflammation, and fibrosis. Further, damage mitigation is associated with reduced apoptosis, preservation of the skin’s antioxidant capacity, and reduction of irreversible DNA and protein oxidation associated with oxidative stress.

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“…Accordingly, the basal cell layer displays weak or absent expression of caspase 14 and, paralleling keratinocytic differentiation, the expression of the protein increases in the stratum spinosum and corneum . Caspase 14 is involved in the cleavage of its cofactor profilaggrin to filaggrin, and filaggrin is expressed and accumulates in the stratum corneum .…”

Section: Introductionmentioning

confidence: 99%