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

Autor(es)

Claro, Sandra ^[1] ; Miyamoto Oshiro, Maria Etsuko ^[1] ; Mortara, Renato Arruda ^[2] ; Paredes-Gamero, Edgar Julian ^[1] ; Silva Pereira, Gustavo Jose ^[3] ; Smaili, Soraya Soubhi ^[3] ; Ferreira, Alice Teixeira ^[1]

Afiliação do(s) autor(es)

^[1] Univ Fed Sao Paulo, Dept Biophys, BR-04023062 Sao Paulo - Brazil

^[2] Univ Fed Sao Paulo, Dept Parasitol, BR-04023062 Sao Paulo - Brazil

^[3] Univ Fed Sao Paulo, Dept Pharmacol, BR-04023062 Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: International Journal of Radiation Biology; v. 90, n. 10, p. 914-927, OCT 2014.
• Citações Web of Science: 5

Resumo

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. (AU)

• Processo FAPESP: 10/00106-5 - Estudo da diferenciação de células tronco mesenquimais e tumorais em células musculares e neuronais enfatizando-se a sinalização de cálcio e a expressão de marcadores após o transplante num modelo de acidente vascular cerebral
• Beneficiário: Alice Teixeira Ferreira
• Linha de fomento: Auxílio à Pesquisa - Regular
• Processo FAPESP: 03/14076-7 - Análise morfológica, bioquímica e funcional da musculatura lisa visceral de ratas e camundongos diabéticos
• Beneficiário: Maria Etsuko Miyamoto Oshiro
• Linha de fomento: Auxílio à Pesquisa - Regular
• Processo FAPESP: 99/10261-7 - Estudo da sinalização, proliferação e transformação celular: redistribuição e compartimentalização de íons receptores e proteoglicanos
• Beneficiário: Alice Teixeira Ferreira
• Linha de fomento: Auxílio à Pesquisa - Programa Equipamentos Multiusuários