A possible role of sphingosine in induction of apoptosis by tumor necrosis factor‐α, in human neutrophils

Ohta, Hideki; Yatomi, Yutaka; Sweeney, Elizabeth; Hakomori, Sen‐itiroh; Igarashi, Yasuyuki

doi:10.1016/0014-5793(94)01218-0

Cited by 182 publications

(141 citation statements)

References 28 publications

Supporting

Mentioning

134

Contrasting

Order By: Relevance

“…Ͻ 30 min) of TNF-␣-induced contractile dysfunction in isolated cardiac myocytes (6), thin strips of isolated muscle (8), as well as in the intact left ventricle (6). Both the time course and absolute values for the TNF-␣-induced increase in free sphingosine levels in intact myocytes are consistent with previously reported values for sphingosine levels obtained from whole cell lipid extracts following TNF-␣ stimulation (40). A second important point shown by Fig.…”

Section: Resultssupporting

confidence: 88%

Sphingosine Mediates the Immediate Negative Inotropic Effects of Tumor Necrosis Factor-α in the Adult Mammalian Cardiac Myocyte

Oral

Dorn

Mann

1997

Journal of Biological Chemistry

308

194

View full text Add to dashboard Cite

To determine whether activation of the neutral sphingomyelinase pathway was responsible for the immediate (<30 min) negative inotropic effects of tumor necrosis factor-␣ (TNF-␣), we examined sphingosine levels in diluent and TNF-␣-stimulated cardiac myocytes. TNF-␣ stimulation of adult feline cardiac myocytes provoked a rapid (<15 min) increase in the hydrolysis of [ 14 C]sphingomyelin in cell-free extracts, as well as an increase in ceramide mass, consistent with cytokine-induced activation of the neutral sphingomyelinase pathway. High performance liquid chromatographic analysis of lipid extracts from TNF-␣-stimulated cardiac myocytes showed that TNF-␣ stimulation produced a rapid (<30 min) increase in free sphingosine levels. Moreover, exogenous D-sphingosine mimicked the effects of TNF-␣ on intracellular calcium homeostasis, as well as the negative inotropic effects of TNF-␣ in isolated contracting myocytes; time course studies showed that exogenous D-sphingosine produced abnormalities in cell shortening that were maximal at 5 min. Finally, blocking sphingosine production using an inhibitor of ceramidase, noleoylethanolamine, completely abrogated the negative inotropic effects of TNF-␣ in isolated contracting cardiac myocytes. Additional studies employing biologically active ceramide analogs and sphingosine 1-phosphate suggested that neither the immediate precursor of sphingosine nor the immediate metabolite of sphingosine, respectively, were likely to be responsible for the immediate negative inotropic effects of TNF-␣. Thus, these studies suggest that sphingosine mediates the immediate negative inotropic effects of TNF-␣ in isolated cardiac myocytes.

show abstract

Section: Resultssupporting

confidence: 88%

Sphingosine Mediates the Immediate Negative Inotropic Effects of Tumor Necrosis Factor-α in the Adult Mammalian Cardiac Myocyte

Oral

Dorn

Mann

1997

Journal of Biological Chemistry

308

194

View full text Add to dashboard Cite

show abstract

“…Although our results show that the apoptosis-inducing action is not specific to sphingosine, and may extend to -erythrosphingosine or stearylamine, a functional role for this sphingolipid in mediating apoptotic signals from different external insults cannot be excluded. Previous studies have demonstrated that sphingosine is an endogenous modulator that mediates apoptotic signals induced by TNFα in neutrophils and cardic myocytes [44,45]. It has also been reported that sphingosine can markedly potentiate the induction of apoptosis by ceramide when present at submicromolar levels, which may also have physiological significance [46].…”

Section: Discussionmentioning

confidence: 98%

Activation of caspase-3-like proteases in apoptosis induced by sphingosine and other long-chain bases in Hep3B hepatoma cells

Hung

Chang

Chuang

1999

Biochemical Journal

View full text Add to dashboard Cite

Sphingosine and other long-chain bases (including sphinganine, dimethylsphingosine and stearylamine), but not octylamine (a short-chain analogue of sphinganine), induced apoptosis in Hep3B hepatoma cells. Because both -and -erythrosphingosine and stearylamine exert potent apoptotic effects on Hep3B cells, it is possible that these long-chain bases may activate apoptosis by inhibiting protein kinase C (PKC) activity. However, pretreatment with the PKC activator PMA could not rescue cells from apoptosis triggered by long-chain bases. Therefore the involvement of PKC in this apoptotic process requires further characterization. We also investigated whether these long-chain bases might be metabolized into ceramide in order to elicit their apoptotic action. We found that long-chain bases acted independently of ceramide in the induction of apoptosis, since addition of fumonisin B1, a fungal agent which effectively inhibits ceramide synthesis from sphingosine, did not protect against apoptosis. Additionally, we found that sphingosine-

show abstract

“…In contrast, SAHA treatment activated JNK, albeit modestly, and associated lethal e ects were partially attenuated by interference with c-Jun transactivation of AP-1. In view of evidence that (1) an intact SAPK-JNK/AP-1 axis is required for the lethal actions of ceramide (Verheij et al, 1996), and (2) perturbations in ceramide and sphingosine metabolism accompany leukemic cell maturation and apoptosis (Ohta et al, 1995), such ®ndings raise the possibility that these lipid messengers may be involved in SAHA-induced apoptosis. Studies designed to test this hypothesis are underway.…”

Section: Discussionmentioning

confidence: 99%

Induction of apoptosis in U937 human leukemia cells by suberoylanilide hydroxamic acid (SAHA) proceeds through pathways that are regulated by Bcl-2/Bcl-XL, c-Jun, and p21CIP1, but independent of p53

et al. 1999

View full text Add to dashboard Cite

Determinants of di erentiation and apoptosis in myelomonocytic leukemia cells (U937) exposed to the novel hybrid polar compound SAHA (suberoylanilide hydroxamic acid) have been examined. In contrast to hexamethylenbisacetamide (HMBA), SAHA-related maturation was limited and accompanied by marked cytoxicity. SAHA-mediated apoptosis occurred within the G 0 G 1 and S phase populations, and was associated with decreased mitochondrial membrane potential, caspase-3 activation, PARP degradation, hypophosphorylation/cleavage of pRB, and down-regulation of c-Myc, c-Myb, and B-Myb. Enforced expression of Bcl-2 or Bclx L inhibited SAHA-induced apoptosis, but only modestly potentiated di erentiation. While SAHA induced the cyclin-dependent kinase inhibitor p21 CIP1 , antisense ablation of this CDKI increased, rather than decreased, SAHA-related lethality. In contrast, conditional expression of wild-type p53 failed to modify SAHA actions, but markedly potentiated HMBA-induced apoptosis. Finally, SAHA modestly increased expression/activation of the stress-activated protein kinase (SAPK/JNK); moreover, SAHA-related lethality was partially attenuated by a dominant-negative c-Jun mutant protein (TAM67). SAHA did not stimulate mitogen-activated protein kinase (MAPK), nor was lethality diminished by the speci®c MEK/MAPK inhibitor PD98059. These ®ndings indicate that SAHA potently induces apoptosis in human leukemia cells via a pathway that is p53-independent but at least partially regulated by Bcl-2/Bcl-x L , p21 CIP1 , and the c-Jun/AP-1 signaling cascade.

show abstract

A possible role of sphingosine in induction of apoptosis by tumor necrosis factor‐α, in human neutrophils

Cited by 182 publications

References 28 publications

Sphingosine Mediates the Immediate Negative Inotropic Effects of Tumor Necrosis Factor-α in the Adult Mammalian Cardiac Myocyte

Sphingosine Mediates the Immediate Negative Inotropic Effects of Tumor Necrosis Factor-α in the Adult Mammalian Cardiac Myocyte

Activation of caspase-3-like proteases in apoptosis induced by sphingosine and other long-chain bases in Hep3B hepatoma cells

Induction of apoptosis in U937 human leukemia cells by suberoylanilide hydroxamic acid (SAHA) proceeds through pathways that are regulated by Bcl-2/Bcl-XL, c-Jun, and p21CIP1, but independent of p53

Contact Info

Product

Resources

About