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- W27832975 abstract "In preliminary studies we showed that basal and insulin-mediated endothelial nitric oxide (NO) synthase phosphorylation (p-eNOS) and NO production are impaired when BAECs are treated with the saturated fatty acid palmitate (P, 500 uM) vs. vehicle (V) for 3 hours (h). Co-incubation of BAECs with the ceramide synthesis inhibitor myriocin (M, 10 μM) negated these effects. ROS can lower NO bioavailability. We determined the contribution from ceramide to P-induced ROS production, and investigated sources of ROS. DCFDA fluorescence was used to assess ROS after BAECs were incubated for 3h with V ± P, M, 10 μM KCN (a mitochondrial ROS inhibitor), or 1 μM NVN (an NADPH oxidase inhibitor). Relative to V, P-evoked increases (2.8±0.1-fold, p<0.05, n=48) in ROS production were blunted (15±5%; p<0.05) but were not completely abolished by M, suggesting the existence of ceramide-dependent and –independent pathways. KCN, NVN, and KCN+NVN lowered (p<0.05) P-evoked ROS production by 37±4%, 18±7%, and 39±12% (n=8–32), respectively, suggesting that in addition to mitochondrial and NADPH oxidase – dependent sources of ROS, additional sources of palmitate-induced ROS exist. P-induced ROS production decreased further when BAECs were co-incubated with M+NVN (46±4%, p<0.05, n=16) vs. NVN alone, but not when M was co-incubated with KCN (n=12) or KCN+NVN (n=16). Moreover, P-evoked increases (p<0.05, n=12) in NADPH oxidase activity were similar in the absence (1.6±0.2-fold) and presence (2.1±0.2-fold) of M. Thus, P-evoked and ceramide-mediated ROS production in BAECs is not derived from NADPH oxidase but may arise from mitochondria. NIHR15HL091493, ADA7-08-RA-164" @default.
- W27832975 created "2016-06-24" @default.
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- W27832975 date "2010-04-01" @default.
- W27832975 modified "2023-09-23" @default.
- W27832975 title "Palmitate evokes ceramide‐dependent reactive oxygen species (ROS) generation from sources other than NADPH oxidase in bovine aortic endothelial cells (BAECs)" @default.
- W27832975 doi "https://doi.org/10.1096/fasebj.24.1_supplement.602.7" @default.
- W27832975 hasPublicationYear "2010" @default.
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