title: Differential degradation of calpastatin by mu- and m-calpain in Ca(2+)-enriched human neuroblastoma LAN-5 cells.
abstract: In neuroblastoma LAN-5 cells during calpain activation, in addition to the two expressed 70 kDa and 30 kDa calpastatin forms, other inhibitory species are produced, having molecular masses of 50 kDa and 15 kDa. At longer times of incubation, both native and new calpastatin species disappear. The formation of these new calpastatins as well as the decrease in intracellular total calpastatin activity are mediated by calpain itself, as indicated by the effect of the synthetic calpain inhibitor I, which prevents both degradative processes. Analysis of the calcium concentrations required for the two processes indicates that the first conservative proteolytic event is mediated by micro-calpain, whereas the second one is preferentially carried out by m-calpain. The appearance of the 15 kDa form, containing only the calpastatin repetitive inhibitory domain and identified also in red cells of hypertensive rats as the major inhibitor form, can be considered a marker of intracellular calpain activation, and it can be used for the monitoring of the involvement of calpain in pathological situations.
authors.affiliation: Department of Experimental Medicine, Biochemistry Section, University of Genoa, Viale Benedetto XV, 1-16132, Genoa, Italy.
authors.forename: R
authors.initials: R
authors.lastname: De Tullio
authors.forename: M
authors.initials: M
authors.lastname: Averna
authors.forename: F
authors.initials: F
authors.lastname: Salamino
authors.forename: S
authors.initials: S
authors.lastname: Pontremoli
authors.forename: E
authors.initials: E
authors.lastname: Melloni
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D002154:Calpain / Q000378:metabolism*; D006801:Humans; D009447:Neuroblastoma / Q000378:metabolism*; D051381:Rats; D014407:Tumor Cells, Cultured
chemical_list: D002135:Calcium-Binding Proteins; C033668:calpastatin; D002154:Calpain; D002118:Calcium