Signaling pathways for sphingosylphosphorylcholine-mediated mitogenesis in Swiss 3T3 fibroblasts.

Desai, Naishadh N.; Carlson, R. O.; Mattie, M. E.; Olivera, Ana; Buckley, Nancy E.; Seki, Takashi; Brooker, Gary; Spiegel, Sarah

doi:10.1083/jcb.121.6.1385

Cited by 118 publications

(84 citation statements)

References 61 publications

(124 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To confirm its LPA-like effects, SPC was applied to oocytes that were voltage-clamped at Ϫ60 mV, and membrane currents were recorded. The SPC preparation obtained from Sigma, which is used by many of the investigators who reported its LPA-like effects (6,11,16,17,(33)(34)(35)(36), elicited oscillatory currents with a threshold concentration in the low micromolar range (Fig. 1).…”

Section: Resultsmentioning

confidence: 99%

“…Electrophysiological Recording from Xenopus Oocytes-Oocytes were obtained from xylazine-anesthetized adult Xenopus laevis frogs (Carolina Scientific, Burlington, NC) under aseptic conditions and were prepared for experiments as described previously (33). Lipids for bioassay were always complexed with fatty acid-free BSA (Sigma, for complexing procedure see below), diluted in frog Na ϩ -Ringer's solution (120 mM NaCl, 2 mM KCl, 1.8 mM CaCl 2 , 5 mM HEPES, pH 7.0), and were applied through superfusion to the oocyte, at a flow-rate of 5 ml/min.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Identification of a Novel Growth Factor-like Lipid, 1-O-cis-Alk-1′-enyl-2-lyso-sn-glycero-3-phosphate (Alkenyl-GP) That Is Present in Commercial Sphingolipid Preparations

Liliom¹,

Fischer²,

Virág³

et al. 1998

Journal of Biological Chemistry

View full text Add to dashboard Cite

Lysophosphatidic acid, a member of the acidic phospholipid autacoid (APA) family of lipid mediators, elicits diverse cellular effects that range from mitogenesis to the prevention of programmed cell death. Sphingosine 1-phosphate and sphingosylphosphorylcholine have also been proposed to be ligands of the APA receptors. However, key observations that provide the foundation of this hypothesis have not been universally reproducible, leading to a controversy in the field. We provide evidence that 1-O-cis-alk-1-enyl-2-lyso-sn-glycero-3-phosphate (alkenyl-GP) is present in some commercial sphingolipid preparations and is responsible for many of their APA-like effects, which were previously attributed to sphingosylphosphorylcholine. Alkenyl-GP was generated by acidic and basic methanolysis from ethanolamine lysoplasmalogen, which was present in the sphingomyelin fraction that is used to manufacture sphingosylphosphorylcholine. We present the structural identification of alkenyl-GP, using 1 H and 13 C NMR, Fourier transform infrared spectrometry, and mass spectrometry. Alkenyl-GP was a potent activator of the mitogen-activated protein kinases ERK1/2 and elicited a mitogenic response in Swiss 3T3 fibroblasts. In contrast, sphingosylphosphorylcholine at a concentration of 10 M was only a weak mitogen and only weakly activated the extracellular signal-regulated protein kinases. Alkenyl-GP has recently been detected as an injury-induced component in the anterior chamber of the eye (Liliom, K., Guan, Z., Tseng, H., Desiderio, D. M., Tigyi, G., and Watsky, M. (1998) Am. J. Physiol. 274, C1065-C1074), indicating that this lipid is a naturally occurring member of the APA mediator family.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Identification of a Novel Growth Factor-like Lipid, 1-O-cis-Alk-1′-enyl-2-lyso-sn-glycero-3-phosphate (Alkenyl-GP) That Is Present in Commercial Sphingolipid Preparations

Liliom¹,

Fischer²,

Virág³

et al. 1998

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…A metabolite of the membrane lipid sphingomyelin, sphingosine (SP), has previously been shown to be a potent inhibitor of PKC, and it has been suggested that SP may be an endogenous inhibitor of PKC in cells [11,12]. Furthermore, SP and its derivatives have been shown to activate the release of sequestered Ca2+ [13][14][15][16][17]. In addition, SPs have been implicated as potent inhibitors of calmodulin-dependent enzymes [18], an interesting observation considering that calmodulin may be of importance in regulating Ca2+ fluxes in FRTL-5 cells [19].…”

Section: Introductionmentioning

confidence: 99%

“…SP derivatives are also potent mitogenic agents, and the mitogenicity may be linked to the formation of arachidonic acid [14,15]. Arachidonic acid and its metabolites may be important in the regulation of Ca2+ entry in FRTL-5 cells [20], and may be of significance in regulating the proliferation of FRTL-5 cells [21].…”

Section: Introductionmentioning

confidence: 99%

Effect of sphingosine derivatives on calcium fluxes in thyroid FRTL-5 cells

Törnquist

Ekokoski

1994

Biochemical Journal

View full text Add to dashboard Cite

show abstract

“…and to stimulate PKC activity [8]. Thus, SphPCho activated two important signal-transduction pathways involved in the regula-…”

mentioning

confidence: 99%

Sphingosylphosphorylcholine Activates an Amiloride‐Nsensitive Na⁺‐H⁺‐Exchange Mechanism in GH₄C₁ Cells

Törnquist

Woodside

Grinstetn

1997

European Journal of Biochemistry

View full text Add to dashboard Cite

The effect of sphingosylphosphorylcholine (SphPCho) on the intracellular pH (pH,) in GH,C, cells was investigated. SphPCho evoked a very slow increase in basal pH,. In cells acidified with nigericin, SphPCho induced a rapid alkalinization of the cells. The effect was inhibited in a Na+-free buffer solution, but was insensitive to ethylisopropyl amiloride, a potent inhibitor of Na+-H+ exchangers (NHE). Reverse transcription and PCR showed that the predominant isoform of the antiport expressed in GH,C, cells is NHE-I. The rate of alkalinization after stimulation with propionate, and after addition of Na' to cells acidified with NH,CI, was enhanced in cells treated with SphPCho. The initial rate of alkalinization after addition of Na' to acidified cells treated with SphPCho gave an apparent K,,, value of 1.5 t 2 mM for Na'. The V,,,, value was 9 2 2 mM H+/min. The effect was insensitive to ouabain, staurosporine and bafilomycin A. However, the SphPCho-evoked alkalinization was abolished in cells treated with 2-deoxy-D-ghcOSe. The effect was not due to the charge of the molecule, as stearylamine increased pH, in Na+-containing and Na+-free buffer. The results show that SphPCho may activate Na+-H' exchange, and that this effect is mediated via an amiloride-insensitive exchange mechanism.

show abstract

Signaling pathways for sphingosylphosphorylcholine-mediated mitogenesis in Swiss 3T3 fibroblasts.

Cited by 118 publications

References 61 publications

Identification of a Novel Growth Factor-like Lipid, 1-O-cis-Alk-1′-enyl-2-lyso-sn-glycero-3-phosphate (Alkenyl-GP) That Is Present in Commercial Sphingolipid Preparations

Identification of a Novel Growth Factor-like Lipid, 1-O-cis-Alk-1′-enyl-2-lyso-sn-glycero-3-phosphate (Alkenyl-GP) That Is Present in Commercial Sphingolipid Preparations

Effect of sphingosine derivatives on calcium fluxes in thyroid FRTL-5 cells

Sphingosylphosphorylcholine Activates an Amiloride‐Nsensitive Na⁺‐H⁺‐Exchange Mechanism in GH₄C₁ Cells

Contact Info

Product

Resources

About

Signaling pathways for sphingosylphosphorylcholine-mediated mitogenesis in Swiss 3T3 fibroblasts.

Cited by 118 publications

References 61 publications

Identification of a Novel Growth Factor-like Lipid, 1-O-cis-Alk-1′-enyl-2-lyso-sn-glycero-3-phosphate (Alkenyl-GP) That Is Present in Commercial Sphingolipid Preparations

Identification of a Novel Growth Factor-like Lipid, 1-O-cis-Alk-1′-enyl-2-lyso-sn-glycero-3-phosphate (Alkenyl-GP) That Is Present in Commercial Sphingolipid Preparations

Effect of sphingosine derivatives on calcium fluxes in thyroid FRTL-5 cells

Sphingosylphosphorylcholine Activates an Amiloride‐Nsensitive Na+‐H+‐Exchange Mechanism in GH4C1 Cells

Contact Info

Product

Resources

About

Sphingosylphosphorylcholine Activates an Amiloride‐Nsensitive Na⁺‐H⁺‐Exchange Mechanism in GH₄C₁ Cells