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Inhibition of glycosphingolipid synthesis by threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (PDMP) and the modulation of IL-1beta-stimulated expression of inducible nitric oxide synthase in rat aortic smooth muscle cells.
Br J Pharmacol 1998; 123(5):906-10BJ

Abstract

1. The composition of glycosphingolipids is altered in atherosclerotic tissue. In order to study the possible modulation of interleukin-1beta (IL-1beta)-induced expression of inducible nitric oxide synthase (iNOS) by endogenously synthesized glycosphingolipids, we investigated rat aortic vascular smooth muscle cells (VSMC) grown in the presence of the inhibitor of glycosphingolipid synthesis, threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (PDMP). 2. Depletion of glycosphingolipids by PDMP (20-30 microM) was demonstrated by thin-layer chromatography of D-[1-(14)C]-galactose- or L-[-U14C]-serine-labelled glycosphingolipids. Nitrite generation was measured by the diaminonaphthalene assay, nitric oxide was determined by the oxyhaemoglobin technique and iNOS protein was detected by immunocytochemistry. 3. In VSMC grown in the presence of PDMP, the glycosphingolipid content was reduced by 30-50%. In PDMP-treated VSMC, IL-1beta (3 micro ml[-1])-stimulated release of nitrite (135 +/- 4 nmol mg(-1) protein 48 h[-1]) was significantly increased as compared to IL-1beta-stimulated control cells (40 +/- 3 nmol mg(-1) protein 48 h(-1); n = 6, P < 0.001). Similarly, IL-1beta (3 micro ml(-1), 36 h)-stimulated release of nitric oxide was higher in PDMP-treated VSMC (6.1 +/- 0.5 nmol mg(-1) protein h[-1]) as compared to untreated cells (2.0 +/- 0.6 nmol mg(-1) protein h(-1); n = 3, P < 0.01). These findings were confirmed by the demonstration of increased expression of iNOS protein (14.9 +/- 1.2% vs 6.4 +/- 0.2%; n = 4, P < 0.001), as shown by immunocytochemistry. 4. Evidence is presented that endogenous glycosphingolipids are important modulators of cytokine-induced iNOS expression. In view of an altered glycosphingolipid profile in atherosclerotic arteries, these mechanisms might be of relevance for the pathogenesis of atherosclerosis and restenosis subsequent to vessel injury.

Authors+Show Affiliations

Medizinische Universitätspoliklinik Bonn, Germany.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

9535019

Citation

Weber, A A., et al. "Inhibition of Glycosphingolipid Synthesis By Threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (PDMP) and the Modulation of IL-1beta-stimulated Expression of Inducible Nitric Oxide Synthase in Rat Aortic Smooth Muscle Cells." British Journal of Pharmacology, vol. 123, no. 5, 1998, pp. 906-10.
Weber AA, Seul C, Harth V, et al. Inhibition of glycosphingolipid synthesis by threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (PDMP) and the modulation of IL-1beta-stimulated expression of inducible nitric oxide synthase in rat aortic smooth muscle cells. Br J Pharmacol. 1998;123(5):906-10.
Weber, A. A., Seul, C., Harth, V., Ko, Y., Seewald, S., Vetter, H., & Sachinidis, A. (1998). Inhibition of glycosphingolipid synthesis by threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (PDMP) and the modulation of IL-1beta-stimulated expression of inducible nitric oxide synthase in rat aortic smooth muscle cells. British Journal of Pharmacology, 123(5), pp. 906-10.
Weber AA, et al. Inhibition of Glycosphingolipid Synthesis By Threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (PDMP) and the Modulation of IL-1beta-stimulated Expression of Inducible Nitric Oxide Synthase in Rat Aortic Smooth Muscle Cells. Br J Pharmacol. 1998;123(5):906-10. PubMed PMID: 9535019.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Inhibition of glycosphingolipid synthesis by threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (PDMP) and the modulation of IL-1beta-stimulated expression of inducible nitric oxide synthase in rat aortic smooth muscle cells. AU - Weber,A A, AU - Seul,C, AU - Harth,V, AU - Ko,Y, AU - Seewald,S, AU - Vetter,H, AU - Sachinidis,A, PY - 1998/4/16/pubmed PY - 1998/4/16/medline PY - 1998/4/16/entrez SP - 906 EP - 10 JF - British journal of pharmacology JO - Br. J. Pharmacol. VL - 123 IS - 5 N2 - 1. The composition of glycosphingolipids is altered in atherosclerotic tissue. In order to study the possible modulation of interleukin-1beta (IL-1beta)-induced expression of inducible nitric oxide synthase (iNOS) by endogenously synthesized glycosphingolipids, we investigated rat aortic vascular smooth muscle cells (VSMC) grown in the presence of the inhibitor of glycosphingolipid synthesis, threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (PDMP). 2. Depletion of glycosphingolipids by PDMP (20-30 microM) was demonstrated by thin-layer chromatography of D-[1-(14)C]-galactose- or L-[-U14C]-serine-labelled glycosphingolipids. Nitrite generation was measured by the diaminonaphthalene assay, nitric oxide was determined by the oxyhaemoglobin technique and iNOS protein was detected by immunocytochemistry. 3. In VSMC grown in the presence of PDMP, the glycosphingolipid content was reduced by 30-50%. In PDMP-treated VSMC, IL-1beta (3 micro ml[-1])-stimulated release of nitrite (135 +/- 4 nmol mg(-1) protein 48 h[-1]) was significantly increased as compared to IL-1beta-stimulated control cells (40 +/- 3 nmol mg(-1) protein 48 h(-1); n = 6, P < 0.001). Similarly, IL-1beta (3 micro ml(-1), 36 h)-stimulated release of nitric oxide was higher in PDMP-treated VSMC (6.1 +/- 0.5 nmol mg(-1) protein h[-1]) as compared to untreated cells (2.0 +/- 0.6 nmol mg(-1) protein h(-1); n = 3, P < 0.01). These findings were confirmed by the demonstration of increased expression of iNOS protein (14.9 +/- 1.2% vs 6.4 +/- 0.2%; n = 4, P < 0.001), as shown by immunocytochemistry. 4. Evidence is presented that endogenous glycosphingolipids are important modulators of cytokine-induced iNOS expression. In view of an altered glycosphingolipid profile in atherosclerotic arteries, these mechanisms might be of relevance for the pathogenesis of atherosclerosis and restenosis subsequent to vessel injury. SN - 0007-1188 UR - https://www.unboundmedicine.com/medline/citation/9535019/Inhibition_of_glycosphingolipid_synthesis_by_threo_1_phenyl_2_decanoylamino_3_morpholino_1_propanol__PDMP__and_the_modulation_of_IL_1beta_stimulated_expression_of_inducible_nitric_oxide_synthase_in_rat_aortic_smooth_muscle_cells_ L2 - https://doi.org/10.1038/sj.bjp.0701674 DB - PRIME DP - Unbound Medicine ER -