gamma-Radiation induces apoptosis via sarcoplasmatic reticulum in guinea pig ileum smooth muscle cells

gamma-Radiation induces apoptosis via sarcoplasmatic reticulum in guinea pig ileum smooth muscle cells

Author Claro, Sandra Autor UNIFESP Google Scholar
Oshiro, Maria Etsuko Miyamoto Autor UNIFESP Google Scholar
Freymuller, Edna Google Scholar
Katchburian, Eduardo Autor UNIFESP Google Scholar
Kallas, Esper George Autor UNIFESP Google Scholar
Cerri, Paulo Sergio Google Scholar
Ferreira, Alice Teixeira Autor UNIFESP Google Scholar
Institution Universidade Federal de São Paulo (UNIFESP)
Universidade de São Paulo (USP)
Abstract We investigated the effects of gamma-radiation on cells isolated from the longitudinal smooth muscle layer of the guinea pig ileum, a relatively radioresistant tissue. Single doses (up to 50 Gy) reduced the amount of sarcoplasmatic reticulum and condensed the myofibrils, as shown by electron microscopy 3 days post-irradiation. After that, contractility of smooth muscle strips was reduced. Ca(2+) handling was altered after irradiation, as shown in fura-2 loaded cells, with elevated basal intracellular Ca(2+), reduced amount of intrareticular Ca(2+), and reduced capacitive Ca(2+) entry. Radiation also induced apoptosis, judged from flow cytometry of cells loaded with proprium iodide. Electron microscopy showed that radiation caused condensation of chromatin in dense masses around the nuclear envelope, the presence of apoptotic bodies, fragmentation of the nucleus, detachment of cells from their neighbors, and reductions in cell volume. Radiation also caused activation of caspase 12. Apoptosis was reduced by the administration of the caspase inhibitor Z-Val-Ala-Asp-fluoromethyl-ketone methyl ester (Z-VAD-FIVIK) during the 3 day period after irradiation, and by the chelator of intracellular Ca(2+), 1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA), from 1 h before until 2 h after irradiation. BAPTA also reduced the effects of radiation on contractility, basal intracellular Ca(2+), amount of intrareticular Ca(2+), capacitative Ca(2+) entry, and apoptosis. in conclusion, the effects of gamma radiation on contractility, Ca(2+) handling, and apoptosis appear due to a toxic action of intracellular Ca(2+). Ca(2+)-induced damage to the sarcoplasmatic reticulum seems a key event in impaired Ca(2+) handling and apoptosis induced by gamma-radiation. (c) 2008 Elsevier B.V. All rights reserved.
Keywords apoptosis
caspase 12
sarco/endoplasmic reticulum
Language English
Sponsor Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Grant number FAPESP: FAPESP-99/10261-7
Date 2008-08-20
Published in European Journal of Pharmacology. Amsterdam: Elsevier B.V., v. 590, n. 1-3, p. 20-28, 2008.
ISSN 0014-2999 (Sherpa/Romeo, impact factor)
Publisher Elsevier B.V.
Extent 20-28
Access rights Closed access
Type Article
Web of Science ID WOS:000258712500003

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