Recent reports have identified the proteasome as the primary degradation pathway for inducible, neuronal and endothelial nitric oxide synthase (NOS). We have demonstrated that hydroxyurea increased nitric oxide (NO) production in endothelial cells through phosphorylation of eNOS as a short-term effect. We find now that NO production in endothelial cells is dose-dependently stimulated by hydroxyurea, as well as both specific and non-specific proteasome inhibitors, as a long term effect. Prolonged treatment of primary human umbilical vein endothelial cells (HUVEC) with hydroxyurea was found to increase eNOS protein levels without an effect on eNOS mRNA levels, suggesting posttranscriptional control. We observed that the inhibitors of proteasomes that we tested also increased eNOS protein levels in HUVEC. In a proteasome assay, we showed that hydroxyurea inhibited protein degradation in a dose-dependent manner, in both purified 20S proteasome and HUVEC lysates. The NO production induced b...y hydroxyurea in endothelial cells appears to be mediated by long term posttranscriptional augmentation in eNOS levels via inhibition of the proteasome activity. Published by Elsevier Inc.
United States Department of Health & Human Services, National Institutes of Health (NIH) - USANIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) [ZIADK025021, Z01DK025016]
TY - JOUR
AU - Čokić, Vladan
AU - Beleslin-Čokić, Bojana
AU - Noguchi, Constance T.
AU - Schechter, Alan N.
PY - 2007
UR - http://rimi.imi.bg.ac.rs/handle/123456789/174
AB - Recent reports have identified the proteasome as the primary degradation pathway for inducible, neuronal and endothelial nitric oxide synthase (NOS). We have demonstrated that hydroxyurea increased nitric oxide (NO) production in endothelial cells through phosphorylation of eNOS as a short-term effect. We find now that NO production in endothelial cells is dose-dependently stimulated by hydroxyurea, as well as both specific and non-specific proteasome inhibitors, as a long term effect. Prolonged treatment of primary human umbilical vein endothelial cells (HUVEC) with hydroxyurea was found to increase eNOS protein levels without an effect on eNOS mRNA levels, suggesting posttranscriptional control. We observed that the inhibitors of proteasomes that we tested also increased eNOS protein levels in HUVEC. In a proteasome assay, we showed that hydroxyurea inhibited protein degradation in a dose-dependent manner, in both purified 20S proteasome and HUVEC lysates. The NO production induced by hydroxyurea in endothelial cells appears to be mediated by long term posttranscriptional augmentation in eNOS levels via inhibition of the proteasome activity. Published by Elsevier Inc.
PB - Academic Press Inc Elsevier Science, San Diego
T2 - Nitric Oxide-Biology & Chemistry
T1 - Hydroxyurea increases eNOS protein levels through inhibition of proteasome activity
EP - 378
IS - 3
SP - 371
VL - 16
DO - 10.1016/j.niox.2007.01.001
UR - conv_1816
ER -
@article{
author = "Čokić, Vladan and Beleslin-Čokić, Bojana and Noguchi, Constance T. and Schechter, Alan N.",
year = "2007",
abstract = "Recent reports have identified the proteasome as the primary degradation pathway for inducible, neuronal and endothelial nitric oxide synthase (NOS). We have demonstrated that hydroxyurea increased nitric oxide (NO) production in endothelial cells through phosphorylation of eNOS as a short-term effect. We find now that NO production in endothelial cells is dose-dependently stimulated by hydroxyurea, as well as both specific and non-specific proteasome inhibitors, as a long term effect. Prolonged treatment of primary human umbilical vein endothelial cells (HUVEC) with hydroxyurea was found to increase eNOS protein levels without an effect on eNOS mRNA levels, suggesting posttranscriptional control. We observed that the inhibitors of proteasomes that we tested also increased eNOS protein levels in HUVEC. In a proteasome assay, we showed that hydroxyurea inhibited protein degradation in a dose-dependent manner, in both purified 20S proteasome and HUVEC lysates. The NO production induced by hydroxyurea in endothelial cells appears to be mediated by long term posttranscriptional augmentation in eNOS levels via inhibition of the proteasome activity. Published by Elsevier Inc.",
publisher = "Academic Press Inc Elsevier Science, San Diego",
journal = "Nitric Oxide-Biology & Chemistry",
title = "Hydroxyurea increases eNOS protein levels through inhibition of proteasome activity",
pages = "378-371",
number = "3",
volume = "16",
doi = "10.1016/j.niox.2007.01.001",
url = "conv_1816"
}
Čokić, V., Beleslin-Čokić, B., Noguchi, C. T.,& Schechter, A. N.. (2007). Hydroxyurea increases eNOS protein levels through inhibition of proteasome activity. in Nitric Oxide-Biology & Chemistry
Academic Press Inc Elsevier Science, San Diego., 16(3), 371-378.
https://doi.org/10.1016/j.niox.2007.01.001
conv_1816
Čokić V, Beleslin-Čokić B, Noguchi CT, Schechter AN. Hydroxyurea increases eNOS protein levels through inhibition of proteasome activity. in Nitric Oxide-Biology & Chemistry. 2007;16(3):371-378.
doi:10.1016/j.niox.2007.01.001
conv_1816 .
Čokić, Vladan, Beleslin-Čokić, Bojana, Noguchi, Constance T., Schechter, Alan N., "Hydroxyurea increases eNOS protein levels through inhibition of proteasome activity" in Nitric Oxide-Biology & Chemistry, 16, no. 3 (2007):371-378,
https://doi.org/10.1016/j.niox.2007.01.001 .,
conv_1816 .
