University of Oulu

Intercellular calcium-mediated cell signaling in keratinocytes cultured from patients with NF1 or psoriasis

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Author: Korkiamäki, Timo1,2
Organizations: 1University of Oulu, Faculty of Medicine, Department of Anatomy and Cell Biology
2University of Oulu, Faculty of Medicine, Department of Dermatology and Venereology
Format: ebook
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 1 MB)
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Language: English
Published: 2002
Publish Date: 2002-09-27
Thesis type: Doctoral Dissertation
Defence Note: Academic Dissertation to be presented with the assent of the Faculty of Medicine, University of Oulu, for public discussion in the Auditorium of the Department of Anatomy and Cell Biology, on September 27th, 2002, at 12 noon.
Reviewer: Professor Veli-Pekka Lehto
Professor Karl Åkerman


Neurofibromatosis type 1 syndrome (NF1) is caused by mutations of the NF1 gene. The NF1 protein (neurofibromin) contains a domain which is related to the GTPase-activating protein (GAP) and accelerates the switch of active Ras-GTP to inactive Ras-GDP. The NF1 protein has been referred to as a tumor suppressor, since the cells of malignant schwannomas of NF1 patients may display a loss of heterozygosity of the NF1 gene. Psoriasis is characterized by hyperproliferation of the epidermis and by down-regulated levels of NF1 mRNA and protein. Ca²⁺ is an universal signal transduction element modulating cell growth and differentiation. Many cell types coordinate their activities by transmitting waves of elevated intracellular calcium levels from cell to cell. The propagation of calcium waves had not been studied previously in human keratinocytes. Thus, the aim of the present study was to find out which pathways may play a role in Ca²⁺ signaling at different extracellular calcium concentrations in NF1 and and psoriatic keratinocytes versus normal control keratinocytes. The results demonstrated that NF1 and psoriatic keratinocytes have a tendency to form cultures characterized by altered Ca²⁺-mediated cell signaling compared to normal keratinocytes. Specifically, the main route of calcium-mediated signaling was gap-junctional in normal keratinocytes. In contrast, ATP-mediated calcium signaling predominated and capacitative calcium influx was defective in NF1 and psoriatic keratinocytes. The results of the present study suggest that mutations of the NF1 tumor suppressor gene or lowered levels of NF1 protein/mRNA may eventually lead to altered intercellular communication.

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Series: Acta Universitatis Ouluensis. D, Medica
ISSN-E: 1796-2234
ISBN: 951-42-6804-0
ISBN Print: 951-42-6803-2
Issue: 695
Copyright information: © University of Oulu, 2002. This publication is copyrighted. You may download, display and print it for your own personal use. Commercial use is prohibited.