Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:1.6.3.1 (
NADPH oxidase
)
11,281
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Increasing evidences suggest that angiotensin (Ang) II participates in the pathogenesis of endothelial dysfunction (ED) through multiple signaling pathways, including angiotensin type 1 receptor (AT
1
R) mediated
NADPH oxidase
(Nox)/reactive oxygen species (ROS) signal transduction. However, the detailed mechanism is not completely understood. In this study, we reported that AngII/AT
1
R-mediated activated protein phosphatase 2A (
PP2A
) downregulated endothelial nitric oxide synthase (eNOS) phosphorylation
via
Nox/ROS pathway. AngII treatment reduced the levels of phosphorylation of eNOS Ser1177 and nitric oxide (NO) content along with phosphorylation of PP2Ac (
PP2A
catalytic subunit) Tyr307, meanwhile increased the
PP2A
activity and ROS production in human umbilical vein endothelial cells (HUVECs). These changes could be impeded by AT
1
R antagonist candesartan (CAN). The pretreatment of 10
-8
M
PP2A
inhibitor okadaic acid (OA) reversed the levels of eNOS Ser1177 and NO content. Similar effects of AngII on
PP2A
and eNOS were also observed in the mesenteric arteries of Sprague-Dawley rats subjected to AngII infusion
via
osmotic minipumps for 2 weeks. We found that the
PP2A
activity was increased, but the levels of PP2Ac Tyr307 and eNOS Ser1177 as well as NO content were decreased in the mesenteric arteries. The pretreatments of antioxidant N-acetylcysteine (NAC) and apocynin (APO) abolished the drop of the levels of PP2Ac Tyr307 and eNOS Ser1177 induced by AngII in HUVECs. The knockdown of p22phox by small interfering RNA (siRNA) gave rise to decrement of ROS production and increment of the levels of PP2Ac Tyr307 and eNOS Ser1177. These results indicated that AngII/AT
1
R pathway activated
PP2A
by downregulating its catalytic subunit Tyr307 phosphorylation, which relies on the Nox activation and ROS production. In summary, our findings indicate that AngII downregulates
PP2A
catalytic subunit Tyr307 phosphorylation to activate
PP2A
via
AT
1
R-mediated Nox/ROS signaling pathway. The activated
PP2A
further decreases levels of eNOS Ser1177 phosphorylation and NO content leading to endothelial dysfunction.
...
PMID:Angiotensin II Decreases Endothelial Nitric Oxide Synthase Phosphorylation
via
AT
1
R Nox/ROS/PP2A Pathway. 3316 96
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