Ceramide Mediates Vascular Dysfunction in Diet-Induced Obesity by PP2A-Mediated Dephosphorylation of the eNOS-Akt Complex

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FIG. 6.
FIG. 6.

Ceramide-associated changes in kinase signaling and O2•−-mediated peroxynitrite formation. BAECs incubated ± pal ± myr for 3 h were treated for the last 10 min ± veh or ins. p-Akt Ser473 and Thr308 to total Akt (n = 12–37 per treatment) (A), p-AMPK T172 to total AMPK (n = 12–15 per treatment) (B), and p-ERK 1/2 to total ERK 1/2 (n = 13–27 per treatment) were not altered by pal (C). D: ESR indicated that 500 μmol/L pal increased cellular O2•− production and that responses could be negated by myr and the O2•− scavengers SOD, PEG-SOD, and tiron (n = 4–18 per treatment). E: Nitrotyrosine formation did not occur in response to 500 μmol/L pal (n = 8–16 per treatment). F: Pal-induced suppression of ins-stimulated p-eNOS to total eNOS could be restored by tiron + myr but not by tiron alone (n = 12–28 per treatment). *P < 0.05 vs. respective veh, #P < 0.05 vs. (+) ins (−) pal. Results represent mean ± SEM. Pal, palmitate; myr, myriocin; veh, vehicle; ins, insulin; PEG, polyethylene glycol.

This Article

  1. Diabetes vol. 61 no. 7 1848-1859