Relationship between protein phosphatase type-2C activity and induction of apoptosis in cultured neuronal cells

• Published in: Neurochemistry international Vol. 41; no. 4; pp. 251 - 259
• Main Authors: Klumpp, Susanne, Selke, Dagmar, Ahlemeyer, Barbara, Schaper, Christine, Krieglstein, Josef
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01-10-2002; Elsevier
• Subjects: Animals; Apoptosis - drug effects; Biological and medical sciences; Caspase-3; Cells, Cultured; Chick Embryo; Chick neurons; Enzyme Activation; Fundamental and applied biological sciences. Psychology; Lipophilicity; Neurons - cytology; Neurons - enzymology; Oleic acid; Oleic Acid - pharmacology; Phosphatases; Phosphoprotein Phosphatases - metabolism; Protein Phosphatase 2; Protein Phosphatase 2C; Saccharomyces cerevisiae Proteins; Unsaturated fatty acids; Unsaturated fatty acids; Phosphatases; Chick neurons; Oleic acid; Caspase-3; Lipophilicity
• ISSN: 0197-0186; 1872-9754
• DOI: 10.1016/S0197-0186(02)00020-7

The cellular composition and concentration of fatty acids are crucial for proliferation and survival. We recently showed stimulation of protein phosphatase type-2C (PP2C) by unsaturated fatty acids. Here, we describe that treatment of cultured chick neurons with 100
μM oleic acid for 24
h increased the percentage of damaged neurons to 61±9% compared with 25±4% in controls. Oleic acid-induced cell death showed features of apoptosis such as chromatin condensation, shrinkage of the nucleus, DNA fragmentation and caspase-3 activation. Extensive studies with a variety of fatty acids revealed a striking correlation between activation of PP2C and induction of apoptosis. Lipophilicity, oxidizability, and an acidic group were required for both effects. In addition, activation of PP2C and induction of apoptosis could discriminate between
cis- and
trans-conformation of the fatty acids. The results are in favor of PP2C playing an important, yet unidentified role in apoptosis.