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Rapamycin affects eIF- 4E expression in rat myocardial fibroblasts infected by Coxsackievirus B3 / 中国当代儿科杂志
Chinese Journal of Contemporary Pediatrics ; (12): 587-590, 2007.
Artículo en Chino | WPRIM | ID: wpr-325663
ABSTRACT
<p><b>OBJECTIVE</b>This study examined the effect of rapamycin, an inhibitor of mammalian target of rapamycin (mTOR), on eukaryotic initiation factor (eIF- 4E) expression in rat myocardial fibroblasts infected by Coxsackievirus B3 (CVB3) in order to identify the drug target for treatment of viral myocarditis.</p><p><b>METHODS</b>Primary cultured rat myocardial fibroblasts were treated with CVB3 with multiplicity of infection (MOI=0.5 PFU/cell). The experiment consisted of four groups in which the cultured rat fibroblasts cells were treated with CVB3, rapamycin (10 nM) and CVB3 + rapamycin or placebo (control). Experimental model of CVB3-infected myocardial fibroblasts was confirmed by detection of CVB3 mRNA expression with RT-PCR and observation of morphological changes of the infected cells with microscopy. eIF-4E expression was determined by both RT-PCR and Western Blot methods.</p><p><b>RESULTS</b>Morphological changes were found in the fibroblasts treated with MOI 0.5 PFU/cell of CVB3 by transmission electron microscope and the viral particles were found in the cytoplasm. CVB3 mRNA was expressed in CVB3-infected fibroblasts after 1, 2, and 3 days after infection and 2 days after passage. The gray scale values of the eIF- 4E /beta -actin in the control, the CVB3, the rapamycin and the CVB3+rapamycin groups were 0.73 +/- 0.07, 0.87 +/- 0.03, 0.32 +/- 0.03 and 0.56 +/- 0.04 respectively detected by RT-PCR, and were 0.79 +/- 0.09, 1.35 +/- 0.12, 0.55 +/- 0.04, and 0.62 +/- 0.07 respectively detected by Western blot. EIF- 4E expression in the CVB3 group was higher than that in the control group. Both the rapamycin and the CVB3+rapamycin groups had lower eIF- 4E expression than the control and the CVB3 groups.</p><p><b>CONCLUSIONS</b>CVB3 can infect myocardial fibroblasts and up-regulate the eIF- 4E expression in rat myocardial fibroblasts. Rapamycin can inhibit eIF- 4E expression and may be a potential medicine for treatment of viral myocarditis. It was suspected that mTOR/eIF- 4E signal pathway in rat myocardial fibroblasts might play an important role in the pathogenesis of viral myocarditis.</p>
Asunto(s)
Texto completo: Disponible Índice: WPRIM (Pacífico Occidental) Asunto principal: Farmacología / Virología / Células Cultivadas / Regulación de la Expresión Génica / Enterovirus Humano B / Sirolimus / Factor 4E Eucariótico de Iniciación / Usos Terapéuticos / Quimioterapia / Infecciones por Enterovirus Tipo de estudio: Estudio pronóstico Límite: Animales Idioma: Chino Revista: Chinese Journal of Contemporary Pediatrics Año: 2007 Tipo del documento: Artículo

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Texto completo: Disponible Índice: WPRIM (Pacífico Occidental) Asunto principal: Farmacología / Virología / Células Cultivadas / Regulación de la Expresión Génica / Enterovirus Humano B / Sirolimus / Factor 4E Eucariótico de Iniciación / Usos Terapéuticos / Quimioterapia / Infecciones por Enterovirus Tipo de estudio: Estudio pronóstico Límite: Animales Idioma: Chino Revista: Chinese Journal of Contemporary Pediatrics Año: 2007 Tipo del documento: Artículo