Activation of calpain precedes morphological alterations during hydrogen peroxide-induced apoptosis in neuronally differentiated mouse embryonal carcinoma P19 cell line

In order to reveal neurodegeneration elicited by reactive oxygen intermedia tes (ROI), neuronally differentiated cells from mouse embryonal carcinoma P 19 cell line were exposed to hydrogen peroxide (H2O2) Enhanced protein-phos phorylation on tyrosine residues was detectable within 5 min of exposure to H2O2, and gradual rises in intracellular free Ca2+ level and in calpain ac tivity were observed. Furthermore, H2O2 stimulation of differentiated P19 c ells for 24 h resulted in morphological alterations in somas as well as neu rites. Also, within 6 h of H2O2 treatment DNA fragmentation has been detect ed. Taken together, these results suggest that oxidative stress induces deg radation of cytoskeletal proteins presumably resulting from increased intra cellular Ca2+ concentration and subsequent activation of calpain. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.