title: Apoptotic cell death of cultured salamander photoreceptors induced by cccp: CsA-insensitive mitochondrial permeability transition.
abstract: Photoreceptor degeneration is mediated by apoptosis in several animal models, although the underlying mechanisms are yet to be elucidated. We present here an apoptotic model based on a primary cell culture of tiger salamander photoreceptors, in which treatment with carbonyl cyanide m-chlorophenylhydrazone (cccp), a protonophore, induced apoptosis. Cells exposed to cccp showed condensed nuclei and displayed positive TdT-dUTP terminal nick-end labeling (TUNEL). In addition, 10-100 microM cccp rapidly induced a reduction of Delta psi(m) and > or = 30 microM cccp induced a significant leakage of calcein from mitochondria to cytosol and nucleus, indicating a change in mitochondrial inner membrane permeability. Cyclosporin A (CsA), a transition pore blocker, did not prevent the cccp-induced MPT or the cccp-evoked apoptotic cell death, suggesting that cccp-induced apoptotic process was mediated by a CsA-insensitive pathway. This cell model provides an in vitro tool for studying mechanisms of photoreceptor apoptosis in isolated photoreceptors and may provide clues to the etiology of retinal degeneration.
authors: Dept of Ophthalmology, Baylor College of Medicine, NC205, Houston, TX 77030-2702, USA. jhyang@bcm.tmc.edu
authors: J H
authors: JH
authors: Yang
authors: R L
authors: RL
authors: Gross
authors: S F
authors: SF
authors: Basinger
authors: S M
authors: SM
authors: Wu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone / Q000494:pharmacology*; D002463:Cell Membrane Permeability; D002478:Cells, Cultured; D016572:Cyclosporine / Q000494:pharmacology*; D008928:Mitochondria / Q000187:drug effects*; D020419:Photoreceptor Cells, Vertebrate / Q000166:cytology / Q000187:drug effects*; D014562:Caudata
chemical_list: D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone; D016572:Cyclosporine