Protein kinase C iota protects neural cells against apoptosis induced by amyloid beta-peptide

Protein kinase C (PKC) isoforms are increasingly recognized as playing impo rtant roles in the regulation of neuronal plasticity and survival. Recent f indings from studies of non-neuronal cells suggest that atypical isoforms o f PKC can modulate apoptosis in various paradigms. Because increasing data support a role for neuronal apoptosis in the pathogenesis of Alzheimer's di sease (AD), we tested the hypothesis that PKCiota (PKCL) can modify vulnera bility of neural cells to apoptosis induced by amyloid beta -peptide (ABP), a cytotoxic peptide linked to neuronal degeneration in AD. Overexpression of PKCL increased the resistance of PC12 cells to apoptosis induced by ABP. Associated with the increased resistance to apoptosis were improved mitoch ondrial function and reduced activity of caspases. In addition, ABP-induced increases in levels of oxidative stress and intracellular calcium levels w ere attenuated in cells overexpressing PKCL. These findings suggest that PK CL prevents apoptosis induced by ABP by interrupting the cell death process at a very early step, thereby allowing the cells to maintain ion homeostas is and mitochondrial function. (C) 2000 Elsevier Science B.V. All rights re served.