Role of sphingomyelin-MAPKs pathway in heat-induced apoptosis.
- Author:
Hyun Sook CHUNG
1
;
So Ra PARK
;
Eun Kyung CHOI
;
Heon Jin PARK
;
Robert J GRIFFIN
;
Chang W SONG
;
HeonJoo PARK
Author Information
1. Department of Microbiology, Inha University, Incheon, Korea. park001@inha.ac.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S.
- Keywords:
apoptosis;
heat-shock;
MAPKs;
SMase
- MeSH:
Apoptosis/*physiology;
Enzyme Activation;
HL-60 Cells;
Heat;
Human;
Mitogen-Activated Protein Kinase Kinases/*metabolism;
Sphingomyelin Phosphodiesterase/*metabolism
- From:Experimental & Molecular Medicine
2003;35(3):181-188
- CountryRepublic of Korea
- Language:English
-
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.
