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(American Journal of Pathology. 2002;160:1981-1990.)
© 2002 American Society for Investigative Pathology


Regular Articles

Altered Calcium-Mediated Cell Signaling in Keratinocytes Cultured from Patients with Neurofibromatosis Type 1

Timo Korkiamäki*, Heli Ylä-Outinen*, Jussi Koivunen*, Seija-Liisa Karvonen*{dagger}{ddagger} and Juha Peltonen*{dagger}§

From the Departments of Anatomy and Cell Biology*and Dermatology,{dagger}University of Oulu, Oulu; the Department of Dermatology,{ddagger}University Hospital of Tampere, Tampere; and the Department of Medical Biochemistry,§University of Turku, Turku, Finland

Capacitative calcium entry and calcium wave propagation were studied in keratinocytes cultured from control persons and patients with type 1 neurofibromatosis. The cells were stimulated mechanically in the presence of inhibitors of gap-junctional or ATP-mediated communication to determine which pathways are operative in Ca2+ signaling between these cells. Keratinocytes cultured from patients with type 1 neurofibromatosis (NF1) had a tendency to form cultures with markedly altered calcium-related signaling characteristics. Specifically, the resting Ca2+ levels, intracellular Ca2+ stores, capacitative calcium influx, and gap-junctional signal transduction were defective in NF1 keratinocytes. Western transfer analysis revealed apparently equal connexin 43 protein levels in normal control and in NF1 keratinocytes. Indirect immunofluorescence, however, demonstrated that connexin 43 was relatively evenly distributed in NF1 cells and did not form typical gap-junctional plaques between keratinocytes. Furthermore, the speed of the calcium wave was reduced in NF1 cells compared to normal keratinocytes. The results demonstrate that keratinocytes cultured from patients with NF1 display altered calcium-mediated signaling between cells.








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Copyright © 2002 by the American Society for Investigative Pathology.