PMID- 12858017 OWN - NLM STAT- MEDLINE DCOM- 20040223 LR - 20091119 IS - 1226-3613 (Print) IS - 1226-3613 (Linking) VI - 35 IP - 3 DP - 2003 Jun 30 TI - Role of sphingomyelin-MAPKs pathway in heat-induced apoptosis. PG - 181-8 AB - 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 43(o)C caused more than 50% of cellular apoptosis within several hours. The neutral-SMase activity in the cells treated for 1 h at 42(o)C was slightly increased but decreased in the cells treated at 43(o)C or 44(o)C for the same period whereas the acid SMase activity was slightly increased after heating the cells at 42(o)C and 43(o)C and markedly increased at 44(o)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. FAU - Chung, Hyun Sook AU - Chung HS AD - Department of Microbiology, Inha University, Incheon, Korea. FAU - Park, So Ra AU - Park SR FAU - Choi, Eun Kyung AU - Choi EK FAU - Park, Heon-Jin AU - Park HJ FAU - Griffin, Robert J AU - Griffin RJ FAU - Song, Chang W AU - Song CW FAU - Park, HeonJoo AU - Park H LA - eng GR - CA 44114/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Exp Mol Med JT - Experimental & molecular medicine JID - 9607880 RN - EC 2.7.12.2 (Mitogen-Activated Protein Kinase Kinases) RN - EC 3.1.4.12 (Sphingomyelin Phosphodiesterase) SB - IM MH - Apoptosis/*physiology MH - Enzyme Activation MH - HL-60 Cells MH - Hot Temperature MH - Humans MH - Mitogen-Activated Protein Kinase Kinases/*metabolism MH - Sphingomyelin Phosphodiesterase/*metabolism EDAT- 2003/07/15 05:00 MHDA- 2004/02/24 05:00 CRDT- 2003/07/15 05:00 PHST- 2003/07/15 05:00 [pubmed] PHST- 2004/02/24 05:00 [medline] PHST- 2003/07/15 05:00 [entrez] AID - 200306306 [pii] AID - 10.1038/emm.2003.25 [doi] PST - ppublish SO - Exp Mol Med. 2003 Jun 30;35(3):181-8. doi: 10.1038/emm.2003.25.