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:2.7.11.31 (
AMP-activated protein kinase
)
13,065
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The extracellular sulfatases (exSulfs)
sulfatase 1
(Sulf1) and sulfatase 2 (Sulf2) are well-known regulators of cell signaling and metabolism. In addition, exSulfs mediate the up- or downregulatory effects of cytokines on angiotensin II (Ang II)-induced expression of hypertensive mediators in vascular smooth muscle cells (VSMC) from spontaneously hypertensive rats (SHRs). Previously, we demonstrated that interleukin-10 (IL-10)-induced dimethylarginine dimethylaminohydrolase-1 (DDAH-1) expression was mediated by Ang II subtype 2 receptor (AT
2
R) and
AMP-activated protein kinase
(
AMPK
) activation, and that IL-10-mediated inhibition of Ang II-induced proliferation of SHRs VSMC was partially associated with DDAH-1. In this study, we examined the effects of exSulfs on IL-10-induced DDAH-1 expression, abrogation of Ang II-induced DDAH-1 downregulation, and inhibition of Ang II-induced proliferation of SHRs VSMC. IL-10-induced DDAH-1 expression and abrogation of Ang II-induced DDAH-1 downregulation were attenuated in Sulf1 siRNA-transfected SHRs VSMC. However, Sulf2 did not affect IL-10-induced DDAH-1 expression and abrogation of Ang II-induced DDAH-1 downregulation. Downregulation of Sulf1 inhibited IL-10-induced AT
2
R expression and the synergistic effects of IL-10 on Ang II-induced AT
2
R expression. Additionally, Sulf1 downregulation inhibited IL-10-induced
AMPK
activity and abrogation of Ang II-induced decrease in
AMPK
activity. Moreover, the IL-10-mediated inhibition of Ang II-induced proliferation was not detected in Sulf1 siRNA-transfected SHRs VSMC; IL-10-mediated inhibition of Ang II-induced VSMC proliferation was mediated via the AT
2
R pathway and
AMPK
activation. Specifically, IL-10-induced DDAH-1 expression, abrogation of Ang II-induced DDAH-1 downregulation, and inhibition of Ang II-induced proliferation, which is mediated by the AT
2
R pathway and
AMPK
activation, are mainly mediated by Sulf1 activity in SHRs VSMC. These results suggest that Sulf1, and not Sulf2, mediates the IL-10-induced inhibition of Ang II-induced hypertensive effects in SHRs VSMC.
...
PMID:Sulfatase 1 mediates IL-10-induced dimethylarginine dimethylaminohydrolase-1 expression and antiproliferative effects in vascular smooth muscle cells of spontaneously hypertensive rats. 3312 21
