Publikationsserver der RWTH Aachen University
Expression und Funktion der Acyl-CoA-Synthetase 5 in der humanen Epidermis
Abstract
dc:descriptionIn epidermal maturation, lipids are necessary both for generation of the epidermal barrier and as intracellular signalling molecules. Various types of lipids including cholesterol derivates and ceramides have been described in this context. Acyl-CoA is involved in different interconnected metabolic pathways, so enzymes with an acyl-CoA-synthetase activity are of great importance within skin lipid metabolism as shown by the example of FATP4 deficient mice. Up to now, there is only few data available regarding to functional relevance of ACSL isoforms in epidermis of human or mouse, especially acyl-CoA synthetase isoform 5 (ACSL5). First of all, ACSL5 expression in human epidermis was investigated in vivo with an histological (mRNA in situ hybridisation, immunohistology) and a molecular (RT-PCR, western blot) approach. The distribution in epidermal tissue showed an expression of ACSL5 associated to epidermal differentiation. Thereby keratinocytes could be indentificated as main source of ACSL5 expressed in human epidermis by several immunohistological stainings. Regarding a possible importance of ACSL5 in cellular lipid metabolism, ACSL5 overexpressing transfectants were established using an human keratinocyte cell line (HaCaT). Some properties of ACSL5 overexpressing HaCaT distinguished from control cultures and were analysed in following examinations. Proliferation assays supported an inhibiting influence on HaCaT proliferation. In organotypic cocultures with human dermal fibroblasts ACSL5 overexpressing HaCaT were restricted in their ability to form a stratified epithelium. Furthermore immunohistological staining against involucrin supported an inhibited cellular differentiation potential as a result of ACSL5 overexpression. Determination of cellular apoptotis showed an increased apoptotic activity in ACSL5 overexpressing HaCaT. In summary, these results show that ACSL5 might be involved in epidermal maturation. It is well known that cellular lipid metabolism can be altered by UVB irradiation in correlation with stress response. UVB irradiation of HaCaT in vitro resulted in slight modification of ACSL5 expression. This could be observed both on RNA and protein level. These observation indicates that ACSL5 might be involved in such processes. But this must be clarified by further examinations. Human epidermal squamous cell carcinomas are characterized as another effect of exposition to UV irradiation. Immunohistological stainings against ACSL5 protein in squamous cell carcinomas showed an decreased ACSL5 expression compared to normal tissue. These observations could be supported by RT-PCR and western blot analysis. But up to now it remains unclear, if acyl-CoA synthetases as ACSL5 may act as a modifying factor in pathogenesis of malignant deseases as the epidermal squamous carcinoma.
Degree
thesis:*- Grantor dc:publisher
- Publikationsserver der RWTH Aachen University
- Year dc:date
- 2010
Author and committee
dc:creator, dc:contributor.*- Author dc:creator
-
- Köster, Jan Christoph
- Contributors dc:contributor
-
- Gaßler, Nikolaus
Subjects
dc:subject × 8Rights
dc:rights- Statement dc:rights
-
- info:eu-repo/semantics/openAccess
- Language dc:language
- ger