gamma-Rays-generated ROS induce apoptosis via mitochondrial and cell cycle alteration in smooth muscle cells

gamma-Rays-generated ROS induce apoptosis via mitochondrial and cell cycle alteration in smooth muscle cells

Author Claro, Sandra Autor UNIFESP Google Scholar
Oshiro, Maria Etsuko Miyamoto Autor UNIFESP Google Scholar
Mortara, Renato Arruda Autor UNIFESP Google Scholar
Paredes-Gamero, Edgar Julian Autor UNIFESP Google Scholar
Silva Pereira, Gustavo Jose Autor UNIFESP Google Scholar
Smaili, Soraya Soubhi Autor UNIFESP Google Scholar
Ferreira, Alice Teixeira Autor UNIFESP Google Scholar
Institution Universidade Federal de São Paulo (UNIFESP)
Abstract Purpose: gamma-rays (IR) cause an increase in intracellular calcium [Ca2+], alters contractility and triggers apoptosis via the activation of protein kinase C in intestinal guinea pig smooth muscle cells. the present study investigated the role of the mitochondria in these processes and characterized proteins involved in IR-induced apoptosis.Materials and methods: Intestinal smooth muscle cells were exposed to 10-50 Gy from a Co-60 gamma-source. Reactive oxygen species (ROS) levels were measured by colourimetry with a fluorescente probe. Protein expression was analyzed by immunoblotting and immunofluorescence.Results: Apoptosis was inhibited by glutathione, possible by inhibiting the generation or scavenging ROS. Apoptosis was mediated by the mitochondria releasing cytochrome c leading to caspase 3 activation. IR increased the expression of the cyclins A, B2 and E and led to unbalanced cellular growth in an absorption dose-dependent manner. However, radiation did not induce alterations in the mitochondrial ultrastructure or in transmembrane electric potential. in contrast, IR increased the nuclear expression of cytoplasmic proteins and cyclins A and E.Conclusion: Smooth muscle cells subjected to IR undergo mitochondrial-mediated apoptosis that involves oncoproteins activation and preserves mitochondrial structure. IR also cause alterations in the expression and localization of both pro- and anti-apoptotic proteins.
Keywords gamma-ray
ROS
apoptosis
mitochondria
cyclins
smooth muscle cells
Language English
Sponsor Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Grant number FAPESP: 99/10261-7
FAPESP: 03/14076-7
FAPESP: 10/00106-5
Date 2014-10-01
Published in International Journal of Radiation Biology. London: Informa Healthcare, v. 90, n. 10, p. 914-927, 2014.
ISSN 0955-3002 (Sherpa/Romeo, impact factor)
Publisher Informa Healthcare
Extent 914-927
Origin http://dx.doi.org/10.3109/09553002.2014.911988
Access rights Closed access
Type Article
Web of Science ID WOS:000343001200012
URI http://repositorio.unifesp.br/handle/11600/38316

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