Role of sphingomyelin-MAPKs pathway in heat-induced apoptosis
Experimental & Molecular Medicine
;
: 181-188, 2003.
Artigo
em Inglês
| WPRIM
| ID: wpr-10313
ABSTRACT
The role of sphingomyelinase (SMase) activation and mitogen activated protein kinases (MAPKs) activation in cellular apoptosis was investigated during the hyperthermic treatment of HL-60 human leukemia cells. Treating the cells for 1 h at 43oC caused more than 50% of cellular apoptosis within several hours. The neutral-SMase activity in the cells treated for 1 h at 42degrees C was slightly increased but decreased in the cells treated at 43degrees C or 44degrees C for the same period whereas the acid SMase activity was slightly increased after heating the cells at 42degrees C and 43degrees C and markedly increased at 44degrees C for 1 h. Treatment of cells with inhibitors of SMase activation and ceramide formation significantly reduced the heat-induced apoptosis. Three major families of mitogen-activated protein kinases (MAPKs) i.e. ERK1/2, p38 and JNK, were activated by the hyperthermic treatment of cells. Inhibition of ERK1/2 with PD98059 exerted little effect on the heat-induced apoptosis and p38 inhibition with SB203580 slightly lessened apoptosis whereas, inhibition of JNK with SP600125 markedly suppressed the heat-induced apoptosis. These results indicate that heat-shock induced the activation of SMase, particularly acid-SMase, thereby causing apoptosis and that JNK played a pivotal role in heat-induced apoptosis in HL-60 leukemia cells.
Texto completo:
DisponíveL
Índice:
WPRIM (Pacífico Ocidental)
Assunto principal:
Esfingomielina Fosfodiesterase
/
Apoptose
/
Células HL-60
/
Quinases de Proteína Quinase Ativadas por Mitógeno
/
Ativação Enzimática
/
Temperatura Alta
Limite:
Humanos
Idioma:
Inglês
Revista:
Experimental & Molecular Medicine
Ano de publicação:
2003
Tipo de documento:
Artigo
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