Data/hora: 08/06/2024 15:46:47

Biblioteca(s): | Embrapa Suínos e Aves.
Data corrente: | 06/08/1998
Data da última atualização: | 11/07/2007
Autoria: | ZANELLA, J. R. C.
Título: | Regulation of cellular growth and programmed cell death by the mycotoxin fumoninsin B1.
Ano de publicação: | 1998
Fonte/Imprenta: | Nebraska: University of Nebraska, 1998.
Páginas: | 185p.
Idioma: | Inglês
Notas: | PhD. Tesis
Conteúdo: | Fumonisin B1 (FB1) is a mycotoxin produced by the fungus Fusarium moniliforme which infects corn and other cereal grains. FB1 is structurally related to sphingolipids and can inhibit ceramide, leading to accumulation of free sphingoid bases. FB1 is xytotoxic to many mammal cells and its effects are species-specific. Several independent studies concluded kidney tissue exhibits high sensitivity to this toxin. FB1 induces cell cycle arrest and apoptosis in normal cells but not in transformed or tumor cell lines. Consequently, it was hypothesized thet FB1 blocks cellular proliferation and induces apoptosis in normal cells but not in trensformed or tumor cells. To test this hypothesis, the mechanism by which FB1 induces cycle arrest and apoptosis was examined. In addition, it was compared to the effects of ceramide, a lipid second messenger known to be involved in signal transduction pathways. This wasaccomplished by using different cell lines originating from different species or tissues. FB1 treatment of CV-1 cells (monkey fibroblasts) induced cell cycle arrest in G1 phase of the cel cycle. Rapid inductionof CDK (cyclin dependent kinase) inhibitors, degradation of cyclin E or CDK2, represion of CDK2 activity, and dephosphorylation of Rb (retinoblastoma) protein occurred. COS-7 cells, CV-1 transformed by the SV40large T antigen, were resistant to the anti-proliferative effects of FB1. Several other tumor cell lines were also resistant to the anti-proliferative effects of FB1. To analyze FB1 induced apoptosis, genes which regulate apoptosis were examined. These studies indicated that FB1 induced apoptosis occurs via the tumor necrosis factor (TNF) pathway and consequently activated caspases. Inactivation of the Rb protein by caspases during FB1 induced apoptosis confirms that growth regulatory genes are targeted by FB1. In conclusion, the results from this study demonstrate that normal cells are susceptible to the anti-proliferative effects of FB1. Prolonged dietary exposure to FB1 could lead to selection of cells which are resistant to apoptosis and normal growth regulation.
Palavras-Chave: | Mycotoxin.
Thesagro: | Fungo; Fusarium Moniliforme; Micotoxina.
Thesaurus Nal: | fumonisin B1; fungi.
Categoria do assunto: | --
Registro original: | Embrapa Suínos e Aves (CNPSA)
Exemplares: | CNPSA - (5369-1) - ADD - TS - -- -  -  - 1998.00965 - DIS