cytochrome-c-t and cypermethrin

This study was undertaken to investigate the effect of cypermethrin on the expression patterns of mRNAs in the striatum of adulthood alone and postnatal pre-exposed followed by adulthood re-exposed rats using discover chips rat microarrays. The expression patterns of V-akt murine thymoma viral oncogene homolog 1, B-cell lymphoma 2 (BCL-2), BCL-2-associated X protein, caspase 1, caspase 9, death-associated protein 3 and interleukin-1β were validated by the qRT-PCR. The expressions of inducible nitric oxide synthase (iNOS) and major histocompatibility complex (MHC) II were assessed immunohistochemically; however, tumour protein p53 and cytochrome c (mitochondrial and cytosolic) expressions were checked at protein level by western blotting. Cypermethrin differentially regulated 65 transcripts at one or the other stage of exposure and 21 transcripts exhibited more pronounced alterations in the postnatal pre-exposed and adulthood re-challenged rats. The results of qRT-PCR were in accordance with the microarray observations and the expressions of iNOS, p53 and cytosolic cytochrome c and MHC II positivity were increased while the level of mitochondrial cytochrome c was reduced in adulthood treated animals. The effects were more pronounced in the postnatal pre-exposed followed by adulthood re-exposed rats. The results obtained thus suggest that multiple pathways are involved in the neurodegeneration as well as in enhancing the vulnerability of neurons in cypermethrin pre-exposed postnatal animals upon re-exposure during adulthood.

Topics: Age Factors; Animals; Animals, Newborn; Apoptosis; Cell Cycle; Corpus Striatum; Cytochromes c; Cytokines; Gene Expression Profiling; Gene Expression Regulation; Insecticides; Male; Oligonucleotide Array Sequence Analysis; Pyrethrins; Rats; RNA, Messenger; Signal Transduction; Tumor Suppressor Protein p53

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