caa a22 4500 475771419 CHVBK 20180406123618.0 cr unu---uuuuu 170329e20000901xx s 000 0 eng 10.1007/s001250051504 doi (NATIONALLICENCE)springer-10.1007/s001250051504 Fatty acids modulate protein kinase C activation in porcine vascular smooth muscle cells independently of their effect on de novo diacylglycerol synthesis [Elektronische Daten] [X. Lu, X.-Y. Yang, R. L. Howard, J. P. Walsh] Aims/hypothesis. Diabetes-induced activation of protein kinase C has been associated with the development of vascular complications. Elevated de novo diacylglycerol synthesis has been postulated to underlie this protein kinase C activation. Diabetes also increases the circulating concentrations of non-esterified fatty acids, which are immediate precursors of diacylglycerol through the de novo pathway. We hypothesized that increased fatty acids contribute to de novo diacylglycerol synthesis and activation of protein kinase C in vascular cells. Methods. Primary cultures of porcine carotid smooth muscle cells were exposed to fatty acids, bound to albumin in physiologic ratios. Diacylglycerol and triacylglycerol were measured in extracts of these cells. Protein kinase C activation was measured as membrane translocation with isoform-specific antibodies. Results. Saturated fatty acids caused considerable accumulation of diacylglycerol through de novo synthesis. Unsaturated fatty acids increased triacylglycerol, but not diacylglycerol. Platelet-derived growth factor activated the α, ɛ and ζ protein kinase C isoforms. Activation of the α and ζ isoforms was amplified by oleate pretreatment but inhibited by palmitate. In the absence of growth factor stimulation, neither palmitate nor oleate had any effect on the membrane/cytosol distribution of any protein kinase C isoform. Conclusion/interpretation. Saturated fatty acids elicited de novo diacylglycerol synthesis in vascular smooth muscle cells without activating protein kinase C. Effects of fatty acids on protein kinase C activation by platelet-derived growth factor did not correlate with the effects on de novo diacylglycerol synthesis. These results indicate that de novo diacylglycerol synthesis is, by itself, insufficient to activate protein kinase C. [Diabetologia (2000) 43: 1136-1143] Springer-Verlag Berlin Heidelberg, 2000 Keywords Diabetes mellitus nationallicence protein kinase C nationallicence diacylglycerol nationallicence non-esterified fatty acids nationallicence platelet-derived growth factor nationallicence vascular smooth muscle nationallicence cultured cells nationallicence Lu X. Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana, USA, IN aut Yang X.-Y Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA, IN aut Howard R. L. Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA, IN aut Walsh J. P. Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA, IN aut https://doi.org/10.1007/s001250051504 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s001250051504 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Lu X. Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana, USA, IN aut NATIONALLICENCE 700 1- Yang X.-Y Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA, IN aut NATIONALLICENCE 700 1- Howard R. L. Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA, IN aut NATIONALLICENCE 700 1- Walsh J. P. Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA, IN aut Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer