Expression and phosphorylation of δ-CaM kinase II in cultured Alzheimer fibroblasts

Chiara Cavazzin, Cristian Bonvicini, Annachiara Nocera, Marco Racchi, Jiro Kasahara, Daniela Tardito, Massimo Gennarelli, Stefano Govoni, Giorgio Racagni, Maurizio Popoli

Research output: Contribution to journalArticlepeer-review

Abstract

Dysregulation of calcium homeostasis is among the major cellular alterations in Alzheimer's disease (AD). We studied Ca2+/calmodulin- dependent protein kinase II (CaM kinase II), one of the major effectors regulating neuronal responses to changes in calcium fluxes, in cultured skin fibroblasts from subjects with sporadic AD. We found, by using PCR and Western analysis, that human fibroblasts express the δ-isoform of this kinase, and that CaM kinase II is the major Ca2+/calmodulin-dependent kinase in these cells. Protein expression level of the kinase was not significantly different in AD fibroblasts. However, the total activity of the kinase (stimulated by Ca2+/calmodulin) was significantly reduced in AD cell lines, whereas Ca2+-independent activity was significantly enhanced. The percent autonomy of the kinase (%Ca2+-independent/Ca 2+-dependent activity) in AD cell lines was 62.8%, three-fold the corresponding percentage in control fibroblasts. The abnormal calcium-independent activity was not due to enhanced basal autophosphorylation of Thr287. The observed abnormalities, if present in brain tissue, may be implicated either in dysfunction of neuroplasticity and cognitive functions or in dysregulation of cell cycle.

Original languageEnglish
Pages (from-to)1187-1196
Number of pages10
JournalNeurobiology of Aging
Volume25
Issue number9
DOIs
Publication statusPublished - Oct 2004

Keywords

  • Alzheimer
  • CaM kinase
  • Human fibroblast
  • Neuroplasticity
  • Protein phosphorylation
  • Signal transduction

ASJC Scopus subject areas

  • Clinical Neurology
  • Biological Psychiatry
  • Developmental Neuroscience
  • Neurology
  • Psychology(all)

Fingerprint Dive into the research topics of 'Expression and phosphorylation of δ-CaM kinase II in cultured Alzheimer fibroblasts'. Together they form a unique fingerprint.

Cite this