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A possible role of sphingosine in induction of apoptosis by tumor necrosis factor‐α, in human neutrophils
Author(s) -
Ohta Hideki,
Yatomi Yutaka,
Sweeney Elizabeth A.,
Hakomori Sen-itiroh,
Igarashi Yasuyuki
Publication year - 1994
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(94)01218-0
Subject(s) - ceramide , sphingosine , apoptosis , lipid signaling , tumor necrosis factor alpha , sphingosine kinase , dna fragmentation , protein kinase c , biology , endogeny , microbiology and biotechnology , sphingolipid , programmed cell death , sphingosine 1 phosphate , kinase , cancer research , biochemistry , immunology , enzyme , receptor
Treatment of human neutrophils with tumor necrosis factor‐α (TNF‐α) resulted in an increase in concentration of ceramide and its catabolite, sphingosine. Sphingosine, a potent endogenous protein kinase C (PKC) inhibitor, as well as TNF‐α, induced internucleosomal DNA fragmentation and morphological changes characteristic of apoptotic cells. Ceramide and sphingosine‐1‐phosphate, the initial product of sphingosine catabolism, did not cause apoptosis under our experimental conditions. In addition, 1‐(5‐isoquinolinesulfonyl)‐2‐methylpiperazine (H7) and N,N ‐dimethylsphingosine (DMS), known as PKC inhibitors, also induced apoptosis, suggesting that induction of apoptosis by sphingosine may be related to inhibition of PKC activity. These results indicate that sphingosine deacylated from ceramide may be an endogenous modulator mediating apoptotic signals by TNF‐α in neutrophils.