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Ultraviolet A and B affect human melanocytes and keratinocytes differently. A study of oxidative alterations and apoptosis
Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology . Linköping University, Faculty of Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology . Linköping University, Faculty of Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Experimental Pathology . Linköping University, Faculty of Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Experimental Pathology . Linköping University, Faculty of Health Sciences.ORCID iD: 0000-0003-4075-159X
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2005 (English)In: Experimental Dermatology, ISSN 0906-6705, Vol. 14, no 2, 117-123 p.Article in journal (Refereed) Published
Abstract [en]

Ultraviolet (UV) radiation is an etiologic agent for malignant melanoma and non-melanoma skin cancer, but the spectral range responsible for tumor induction is still to be elucidated. In this study, we compared effects of UVA and UVB irradiation on normal human melanocytes (MCs) and keratinocytes (KCs) in vitro. We demonstrate that UVA irradiation induces immediate loss of reduced glutathione (GSH) in both MCs and KCs. Exposure to UVA also causes reduced plasma membrane stability, in both cell types, as estimated by fluorescein diacetate retention and flow cytometry. Furthermore, we noted reduction in proliferation and higher apoptosis frequency 24 h after UVA irradiation. UVB irradiation of KCs caused instant reduction of reduced GSH and impaired plasma membrane stability. We also found decline in proliferation and increased apoptosis after 24 h. In MCs, on the other hand, UVB had no effect on GSH level or plasma membrane stability, although increased apoptotic cell death and reduced proliferation was detected. In summary, MCs and KCs showed similar response towards UVA, while UVB had more pronounced effects on KCs as compared to MCs. These results might have implications for the induction of malignant melanoma and non-melanoma skin cancer.

Place, publisher, year, edition, pages
2005. Vol. 14, no 2, 117-123 p.
Keyword [en]
apoptosis, keratinocyte, melanocyte, oxidative stress, UV irradiation
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-14497DOI: 10.1111/j.0906-6705.2005.00238.xOAI: oai:DiVA.org:liu-14497DiVA: diva2:23596
Available from: 2008-11-14 Created: 2008-11-14 Last updated: 2017-08-30
In thesis
1. UVA/B induced redox alterations and apoptosis in human melanocytes
Open this publication in new window or tab >>UVA/B induced redox alterations and apoptosis in human melanocytes
2007 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Malignant melanoma is one of the most rapidly increasing cancers and accounts for about three-quarter of all skin cancer deaths worldwide. Despite compelling evidence that ultraviolet (UV) irradiation causes melanoma the knowledge how various wavelength spectra affect the balance between proliferation and apoptosis controlling the homeostasis of the melanocyte population is still limited. The aim of this thesis was to elucidate the regulation of UVA/B induced apoptotic signaling in human epidermal melanocytes in vitro in relation to redox alterations and antioxidant photoprotection.

UVA irradiation induced changes in plasma membrane stability, decreased cell proliferation and increased apoptosis. In comparison, melanocyte plasma membrane was markedly resistant to UVB irradiation although apoptosis was triggered. Thus, UVA irradiation should not be overlooked as an etiologic factor in melanoma development. Further, after irradiation with UVA/B we found alterations in redox state manifested by a reduction of intracellular GSH levels, translocation of nuclear factor-κB from the cytosol to the nucleus, an increase of γ-glutamylcysteine synthetase, the rate-limiting enzyme in GSH synthesis, and an increased apoptosis frequency. α-Tocopherol provided photoprotection through several modes of action affecting redox alterations and signaling, stabilizing the plasma membrane, and decreased proliferation and apoptosis rate, while β-carotene did not show the same protective capacity. Altogether, α-tocopherol might be a useful substance in protecting melanocytes from UV induced damage.

We demonstrate UVA/B irradiation to activate the intrinsic pathway of apoptosis in melanocytes where translocation of Bcl-2 family proteins to the mitochondria modulates the apoptosis signal. Interestingly, the anti-apoptotic Bcl-2 family proteins generally thought to be attached to membranes, were localized in the cytosol before UV irradiation and translocated to the mitochondria in the surviving population, which might be a critical event in preventing apoptotic cell death. Lysosomal cathepsins were released to the cytosol acting as pro-apoptotic mediators upstream of activation and translocation of Bax to the mitochondria. When melanocytes were exposed to UVA, p53 participated in apoptosis regulation through interaction with Bcl-2 family proteins, while UVB induced p53-transcriptional activity and apoptosis involving lysosomal membrane permeabilization. Thus, depending on the UV wavelength p53 mediated apoptosis in melanocytes by transcriptional dependent or independent activity. These results emphasize p53 as an important pro-apoptotic component in the regulation of apoptosis.

This thesis gives new insight in the harmful and various effects of different wavelengths within the UV spectrum on human melanocytes in vitro. Improved knowledge of the apoptosis regulatory systems in melanocytes might lead to a better understanding of the formation of pigment nevi and malignant melanoma and, in the future, provide better strategies to prevent and eliminate tumor development and progression.

Place, publisher, year, edition, pages
Institutionen för biomedicin och kirurgi, 2007. 58 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1004
Keyword
UV, melanocyte, apoptosis, glutathione, p53
National Category
Dermatology and Venereal Diseases
Identifiers
urn:nbn:se:liu:diva-8880 (URN)978-91-85831-84-5 (ISBN)
Public defence
2007-06-05, Berzeliussalen, Campus US, Ingång 65, Hälsouniversitetet, Linköpings universitet, SE-581 85 Linköping, 13:00 (English)
Opponent
Supervisors
Available from: 2007-05-21 Created: 2007-05-21 Last updated: 2017-08-30

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Larsson (Wäster), PetraAndersson, EvaJohansson, UnoÖllinger, KarinRosdahl, Inger

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