Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.31 (AMP-activated protein kinase)
 13,065 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

AMP-activated protein kinase (AMPK) activation plays a central role in cellular metabolic homeostasis. Although AMPK is known for its roles in energy homeostasis, numerous recent studies have suggested broader protective roles in inflammation and hypertension. Chemokine CCL5 has shown down-regulatory effects on angiotensin II (Ang II)-induced hypertensive mediators as well as VSMCs proliferation in spontaneously hypertensive rats (SHR) VSMCs. In the present study, we investigated the relationship between CCL5 and AMPK in the anti-hypertensive effects of CCL5 in SHR VSMCs. CCL5 increased AMPK phosphorylation and attenuated Ang II-induced AMPK inhibition. AMPK activation induced by CCL5 was mediated mainly through the AT2 R pathway. Activation of dimethylarginine dimethylaminohydrolase (DDAH)-1 by CCL5 resulted in AMPK activation as well as attenuation of Ang II-induced AMPK inhibition. In addition, AMPK activation induced by CCL5 was partially responsible for the inhibitory effects of CCL5 on Ang II-induced 12-lipoxygenase (12-LO) and endothelin (ET)-1 expression, and the inhibitory effect of CCL5 on Ang II-induced VSMCs proliferation was also mediated via AMPK activation in SHR VSMCs. In conclusion, CCL5 induces activation of AMPK via DDAH-1 activity in SHR VSMCs, and activation of AMPK is partially responsible for the inhibitory effects of CCL5 on Ang II-induced hypertensive mediators. These results suggest that activation of AMPK by CCL5 potentially expands the anti-hypertensive role of CCL5 in SHR VSMCs.
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PMID:CCL5 upregulates activation of AMP-activated protein kinases in vascular smooth muscle cells of spontaneously hypertensive rats. 2465 27

In hypertension studies, anti-inflammatory cytokine interleukin-10 (IL-10) has been shown to prevent angiotensin II (Ang II)-induced vasoconstriction and regulate vascular function by down-regulating pro-inflammatory cytokine and superoxide production in vascular cells. However, little is known about the mechanism behind the down-regulatory effect of IL-10 on Ang II-induced hypertensive mediators. In this study, we demonstrated the effects of IL-10 on expression of dimethylarginine dimethylaminohydrolase (DDAH)-1, a regulator of NO bioavailability, as well as the down-regulatory mechanism of action of IL-10 in relation to Ang II-induced hypertensive mediator expression and cell proliferation in vascular smooth muscle cells (VSMCs) from spontaneously hypertensive rats (SHR). IL-10 increased DDAH-1 but not DDAH-2 expression and increased DDAH activity. Additionally, IL-10 attenuated Ang II-induced DDAH-1 inhibition in SHR VSMCs. Increased DDAH activity due to IL-10 was mediated mainly through Ang II subtype II receptor (AT2 R) and AMP-activated protein kinase (AMPK) activation. DDAH-1 induced by IL-10 partially mediated the inhibitory action of IL-10 on Ang II-induced 12-lipoxygenase (LO) and endothelin (ET)-1 expression in SHR VSMCs. In addition, the inhibitory effect of IL-10 on proliferation of Ang II-induced VSMCs was mediated partially via DDAH-1 activity. These results suggest that DDAH-1 plays a potentially important role in the anti-hypertensive activity of IL-10 during Ang II-induced hypertension.
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PMID:Dimethylarginine dimethylaminohydrolase-1 mediates inhibitory effect of interleukin-10 on angiotensin II-induced hypertensive effects in vascular smooth muscle cells of spontaneously hypertensive rats. 2637 20

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 (AT2 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 AT2 R expression and the synergistic effects of IL-10 on Ang II-induced AT2 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 AT2 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 AT2 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.
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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