Exp Mol Med.  2003 Jun;35(3):181-188.

Role of sphingomyelin-MAPKs pathway in heat-induced apoptosis

Affiliations
  • 1Department of Microbiology, Inha University, Incheon, Korea. park001@inha.ac.kr
  • 2Department of Physiology, Inha University, Incheon, Korea.
  • 3Department of Therapeutic Radiology, University of Ulsan, Seoul, Korea.
  • 4Department of Statictics Inha University, Incheon, Korea.
  • 5Department of Radiation Oncology Univerisity of Minnesota, Ninneapolis, MN, USA.

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.

Keyword

apoptosis; heat-shock; MAPKs; SMase

MeSH Terms

Apoptosis/*physiology
Enzyme Activation
HL-60 Cells
Heat
Human
Mitogen-Activated Protein Kinase Kinases/*metabolism
Sphingomyelin Phosphodiesterase/*metabolism
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