MEK/ERK pathway protects ionizing radiation-induced loss of mitochondrial membrane potential and cell death in lymphocytic leukemia cells.
Cell Death Differ
; 9(9): 963-71, 2002 Sep.
Article
em En
| MEDLINE
| ID: mdl-12181747
ABSTRACT
MEK/ERK-mediated signals have recently been found to inhibit Fas-mediated cell death through inhibition of caspase-8 activity. It remains unknown whether MEK/ERK-mediated signals affect ionizing radiation (IR)-induced cell death. Here we demonstrate that MEK/ERK-mediated signals selectively inhibit IR-induced loss of mitochondrial membrane potential (DeltaPsi(m)) and subsequent cell death. In Jurkat cells, TPA strongly activated ERK and inhibited the IR-induced caspase-8/Bid cleavage and the loss of DeltaPsi(m). The inhibitory effect of TPA was mostly abrogated by pretreatment of a specific MEK inhibitor PD98059, indicating that the effect depends upon MEK/ERK-mediated signals. Moreover, BAF-B03 transfectants expressing IL-2 receptor (IL-2R) beta(c) chain lacking the acidic region, which is responsible for MEK/ERK-mediated signals, revealed higher sensitivity to IR than the transfectants expressing wild-type IL-2R. Interestingly, the signals could neither protect the DeltaPsi(m) loss nor cell death in UV-irradiated cells. These data imply that the anti-apoptotic effect of MEK/ERK-mediated signals appears to selectively inhibit the IR-induced cell death through protection of the DeltaPsi(m) loss. Our data enlighten an anti-apoptotic function of MEK/ERK pathway against IR-induced apoptosis, thereby implying its contribution to radioresistance.
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Base de dados:
MEDLINE
Assunto principal:
Morte Celular
/
Proteínas Serina-Treonina Quinases
/
Células Jurkat
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Quinases de Proteína Quinase Ativadas por Mitógeno
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Proteínas Quinases Ativadas por Mitógeno
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Membranas Intracelulares
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Mitocôndrias
Idioma:
En
Ano de publicação:
2002
Tipo de documento:
Article