Protein kinase C iota protects neural cells against apoptosis induced by amyloid beta-peptide.
Protein kinase C (PKC) isoforms are increasingly recognized as playing important roles in the regulation of neuronal plasticity and survival. Recent findings from studies of non-neuronal cells suggest that atypical isoforms of PKC can modulate apoptosis in various paradigms. Because increasing data support a role for neuronal apoptosis in the pathogenesis of Alzheimer's disease (AD), we tested the hypothesis that PKCiota (PKCiota) can modify vulnerability of neural cells to apoptosis induced by amyloid beta-peptide (ABP), a cytotoxic peptide linked to neuronal degeneration in AD. Overexpression of PKCiota increased the resistance of PC12 cells to apoptosis induced by ABP. Associated with the increased resistance to apoptosis were improved mitochondrial function and reduced activity of caspases. In addition, ABP-induced increases in levels of oxidative stress and intracellular calcium levels were attenuated in cells overexpressing PKCiota. These findings suggest that PKCiota prevents apoptosis induced by ABP by interrupting the cell death process at a very early step, thereby allowing the cells to maintain ion homeostasis and mitochondrial function.
Xie
J
J
Sanders-Brown Center on Aging and Department of Anatomy and Neurobiology, University of Kentucky, Lexington, KY 40536, USA.
Guo
Q
Q
Zhu
H
H
Wooten
M W
MW
Mattson
M P
MP
D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D008928:Mitochondria / Q000502:physiology; D018384:Oxidative Stress / Q000187:drug effects; D016716:PC12 Cells; D010446:Peptide Fragments / Q000633:toxicity*; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D011994:Recombinant Proteins / Q000378:metabolism; D014162:Transfection; D000099293:Protein Kinase C-lambda
D016229:Amyloid beta-Peptides; D002118:Calcium; D053148:Caspase 3; D020169:Caspases; D007527:Isoenzymes; D010446:Peptide Fragments; D011493:Protein Kinase C; D011994:Recombinant Proteins; D000099293:Protein Kinase C-lambda; C074636:amyloid beta-protein (25-35); C505410:Casp3 protein, rat