cytochrome-c-t and fenvalerate

The endoplasmic reticulum (ER) serves as a critical site of protein synthesis and processing. The temperature-sensitive hamster fibroblast cell line (tsBN7) displays deficient N-linked glycosylation activity at the restrictive temperature and activates cellular apoptosis. Temperature-shifted tsBN7 cells display induction of Grp78 and Gadd153, genes known to be induced by ER stress, and activate apoptosis via the release of cytochrome c from the mitochondria. Cyclosporin A (CsA), a potent blocker of the mitochondrial permeability transition pore (PTP), was sufficient to block cytochrome c release and to rescue tsBN7 cells from apoptosis. CsA-treated cells displayed Grp78 induction at the restrictive temperature, consistent with an ER stress signal being carried to the nucleus, while the apoptosis-associated transcription factor, Gadd153, displayed only a mild induction. Cypermethrin, a type II pyrethroid known to perturb Ca(2+) signaling in neuronal cells, was sufficient to arrest apoptosis under these conditions. This work identifies type II pyrethroids as a valuable new tool in the characterization of cellular stress signaling pathways.

Topics: Animals; Apoptosis; Blotting, Western; Caspase 12; Caspase Inhibitors; Caspases; CCAAT-Enhancer-Binding Proteins; Cell Line; Cell Survival; Cricetinae; Cyclosporine; Cytochromes c; Endoplasmic Reticulum; Endoplasmic Reticulum Chaperone BiP; Fibroblasts; Glycosylation; Heat-Shock Proteins; In Situ Nick-End Labeling; Insecticides; Ion Channels; JNK Mitogen-Activated Protein Kinases; MAP Kinase Kinase 4; Mitochondria; Mitochondrial Membrane Transport Proteins; Mitochondrial Permeability Transition Pore; Mitogen-Activated Protein Kinase Kinases; Molecular Chaperones; Nitriles; p38 Mitogen-Activated Protein Kinases; Phosphorylation; Pyrethrins; Signal Transduction; Tacrolimus; Temperature; Thapsigargin; Transcription Factor CHOP; Transcription Factors; Tunicamycin; Ultraviolet Rays