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  • Title: Advanced glycosylation end products increase diacylglycerol levels in cultured human umbilical vein endothelial cells.
    Author: Yan J, Liu N.
    Journal: Chin Med J (Engl); 2000 Jul; 113(7):588-91. PubMed ID: 11776023.
    Abstract:
    OBJECTIVE: To study whether the diacylglycerol (Dia) signaling pathway is stimulated by advanced glycosylation end products (AGEP) and to test the effect of vitamin E and aminoguanidine (AG) on the elevation of Dia induced by AGEP in cultured human umbilical vein endothelial cells (HUVECs). METHODS: The effects of AGEP on Dia levels in cultured HUVEC were studied with radio-enzymatic assay. Quantitative measurements of 32P phosphatidic acid were achieved by thin-layer chromatography and autoradiography. RESULTS: The Dia levels in HUVECs were increased by AGEP modified bovine serum albumin (AGEP-BSA) in a dose-dependent, biphasic manner. The early phase was rapid and transient, peaking at 15 s; the late phase reached the maximal level at 10 min and then decayed slowly. Dia levels in HUVEC exposed to different concentrations (50, 100 and 200 mg/L) of AGEP-BSA (341 +/- 14, 678 +/- 16, and 873 +/- 18 pmol/L, respectively vs control 225 +/- 10 pmol/L) and AGEP-BSA samples with various glycosylation times (4, 8 and 12 weeks) were significantly increased (270 +/- 12, 394 +/- 16, and 556 +/- 19 pmol/L) as compared with the controls. 50 and 100 mmol/L of vitamin E can reduce AGEP-BSA-induced Dia levels from 873 +/- 18 pmol/L to 764 +/- 29 and 441 +/- 21 pmol/L in HUVEC, respectively. In AG-treated (100 mmol/L) groups, the same concentration (100 and 200 mg/L) of AGEP-BSA-induced elevation of Dia was decreased to 312 +/- 8 and 351 +/- 13 pmol/L, respectively. Glycosylated low-density lipoprotein (LDL) did not affect Dia levels. CONCLUSION: AGEP causes a robust stimulation of the Dia/protein kinase C pathway in HUVEC. Vitamin E can attenuate the AGEP-BSA-induced elevation of Dia levels. AG can suppress the ability of AGEP-BSA to increase Dia levels in HUVEC.
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