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

• Published in: Neurobiology of aging Vol. 25; no. 9; pp. 1187 - 1196
• Main Authors: Cavazzin, Chiara, Bonvicini, Cristian, Nocera, Annachiara, Racchi, Marco, Kasahara, Jiro, Tardito, Daniela, Gennarelli, Massimo, Govoni, Stefano, Racagni, Giorgio, Popoli, Maurizio
• Format: Journal Article
• Language: English
• Published: London Elsevier Inc 01.10.2004; Elsevier Science
• Subjects: Aged; Alzheimer; Alzheimer Disease - enzymology; Alzheimer Disease - genetics; Alzheimer Disease - physiopathology; Biological and medical sciences; Calcium - metabolism; Calcium - pharmacology; Calcium Signaling - drug effects; Calcium Signaling - genetics; Calcium-Calmodulin-Dependent Protein Kinase Type 2; Calcium-Calmodulin-Dependent Protein Kinases - drug effects; Calcium-Calmodulin-Dependent Protein Kinases - genetics; Calcium-Calmodulin-Dependent Protein Kinases - metabolism; Calmodulin - metabolism; Calmodulin - pharmacology; CaM kinase; Cells, Cultured; Cognition Disorders - enzymology; Cognition Disorders - genetics; Cognition Disorders - physiopathology; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Female; Fibroblasts - cytology; Fibroblasts - enzymology; Human fibroblast; Humans; Isoenzymes - genetics; Isoenzymes - metabolism; Male; Medical sciences; Middle Aged; Neurology; Neuronal Plasticity - genetics; Neuroplasticity; Phosphorylation; Protein phosphorylation; RNA, Messenger - metabolism; Signal transduction; Signal Transduction - drug effects; Signal Transduction - genetics; Threonine - metabolism; Neuroplasticity; Signal transduction; Human fibroblast; Protein phosphorylation; Alzheimer; CaM kinase; Human; Nervous system diseases; Phosphorylation; calmodulin-dependent protein kinase; Enzyme; Alzheimer disease; Transferases; Gene expression; Cerebral disorder; Central nervous system disease; Degenerative disease; Fibroblast; Ca
• ISSN: 0197-4580; 1558-1497
• DOI: 10.1016/j.neurobiolaging.2003.12.003

Dysregulation of calcium homeostasis is among the major cellular alterations in Alzheimer’s disease (AD). We studied Ca 2+/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 Ca 2+/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 Ca 2+/calmodulin) was significantly reduced in AD cell lines, whereas Ca 2+-independent activity was significantly enhanced. The percent autonomy of the kinase (%Ca 2+-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 Thr 287. 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.