Activation of AMP-Activated Protein Kinase Inhibits the Proliferation of Human Endothelial Cells

Peyton, Kelly J.; Liu, Xiaoming; Yan, Yu; Yates, Benjamin; Durante, William

doi:10.1124/jpet.112.194712

Cited by 42 publications

(44 citation statements)

References 52 publications

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“…Interestingly, 2 studies on AMPK effects in cultured endothelial cells in which A769662 was used as AMPK stimulator report 3-to 5-fold higher A769662 concentrations than used in our study which might suggest that relatively high concentrations are necessary for endothelial AMPK stimulation. 29,30 A recent study demonstrating loss of endothelium-dependent dilation by hyperpolarization (EDH-dependent dilation) after endothelium-specific knockout of the α 1 subunit 17 does not contradict our results either, because in these experiments only the endothelium was stimulated (with acetylcholine) but not the smooth muscle. Our studies indicate for the first time that microvessels can be dilated via AMPK stimulation directly in smooth muscle and this finding may be important for treatment strategies in cardiovascular diseases being associated with loss or severe impairment of endothelial function.…”

Section: Discussioncontrasting

confidence: 39%

AMPK Dilates Resistance Arteries via Activation of SERCA and BK _Ca Channels in Smooth Muscle

et al. 2015

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Section: Discussioncontrasting

confidence: 39%

AMPK Dilates Resistance Arteries via Activation of SERCA and BK _Ca Channels in Smooth Muscle

et al. 2015

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“…Human aortic endothelial cells (HAECs) and human umbilical vein endothelial cells (HUVECs) were purchased from Lonza Incorporated (Allendale, NJ) and propagated in M199 medium supplemented with 20% bovine calf serum, 2 mM L-glutamine, 50 g/ml endothelial cell growth factor, 90 g/ml heparin, and 100 U/ml of penicillin and streptomycin (36). Murine aortic endothelial cells (MAECs) from wild-type (HO-1 ϩ/ϩ ) and HO-1-deficient (HO-1 Ϫ/Ϫ ) mice were initially provided by Dr. Anupam Agarwal (Division of Nephrology, University of Alabama at Birmingham) and subsequently isolated from mice by plating thoracic aortas on Matrigel-coated plates and purifying MAEC outgrowth with a PECAM-1 antibody, as we previously described (23).…”

Section: Methodsmentioning

confidence: 99%

Physiological cyclic strain promotes endothelial cell survival via the induction of heme oxygenase-1

Liu

Peyton

Durante

2013

American Journal of Physiology-Heart and Circulatory Physiology

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Endothelial cells (ECs) are constantly subjected to cyclic strain that arises from periodic change in vessel wall diameter as a result of pulsatile blood flow. Application of physiological levels of cyclic strain inhibits EC apoptosis; however, the underlying mechanism is not known. Since heme oxygenase-1 (HO-1) is a potent inhibitor of apoptosis, the present study investigated whether HO-1 contributes to the antiapoptotic action of cyclic strain. Administration of physiological cyclic strain (6% at 1 Hz) to human aortic ECs stimulated an increase in HO-1 activity, protein, and mRNA expression. The induction of HO-1 was preceded by a rise in reactive oxygen species (ROS) and Nrf2 protein expression. Cyclic strain also stimulated an increase in HO-1 promoter activity that was prevented by mutating the antioxidant responsive element in the promoter or by overexpressing dominant-negative Nrf2. In addition, the strain-mediated induction of HO-1 and activation of Nrf2 was abolished by the antioxidant N-acetyl-l-cysteine. Finally, application of cyclic strain blocked inflammatory cytokine-mediated EC death and apoptosis. However, the protective action of cyclic strain was reversed by the HO inhibitor tin protoporphyrin-IX and was absent in ECs isolated from HO-1-deficient mice. In conclusion, the present study demonstrates that a hemodynamically relevant level of cyclic strain stimulates HO-1 gene expression in ECs via the ROS-Nrf2 signaling pathway to inhibit EC death. The ability of cyclic strain to induce HO-1 expression may provide an important mechanism by which hemodynamic forces promote EC survival and vascular homeostasis.

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“…AICAR plays a central role in the metabolism and in signal transduction increasing insulin properties, up-regulating mitochondrial enzymes in muscles and decreasing intra-abdominal fat [2][3][4] . It can act as an agonist and antagonist for a number of enzymes crucial for the cell life; among these, AMPKa has a fundamental role in energy homeostasis, being an energy sensor implicated in various 24,25 . Interestingly, in terms of cell proliferation, we have tested ERK1/2 phosphorylation: according to the MTT results, at 2 h of incubation, ERK1/2 phosphorylation was down regulated in treated cells (data not shown).…”

Section: Discussionmentioning

confidence: 99%

New synthetic AICAR derivatives with enhanced AMPK and ACC activation

Scudiero¹,

Nigro

Monaco

et al. 2015

Journal of Enzyme Inhibition and Medicinal Chemistry

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5-Aminoimidazole-4-carboxamide riboside (AICAR) has an important role in the regulation of the cellular metabolism showing a broad spectrum of therapeutic activities against different metabolic processes. Due to these proven AICAR properties, we have designed, synthesized and tested the biological activity of two ribose-modified AICAR derivatives, named A3 and A4, in comparison to native AICAR and its 5 0 -phosphorylated counterpart ZMP. Our findings have shown that A3 and A4 derivatives induce the phosphorylation of 5 0 -AMP activated protein kinase a (AMPKa), which leads to the inhibition of acetyl-CoA carboxylase (ACC), and downregulate the activity of the extracellular signal-regulated kinases (ERK1/2). Cytotoxicity tests demonstrated that A3 and A4 do not significantly reduce cell viability up to 24 h. Taken together our results indicate that A3 and A4 have a comparable activity to AICAR and ZMP at 0.5 and 1 mM suggesting their potential use in future pharmacological strategies relating to metabolic diseases.

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Activation of AMP-Activated Protein Kinase Inhibits the Proliferation of Human Endothelial Cells

Cited by 42 publications

References 52 publications

AMPK Dilates Resistance Arteries via Activation of SERCA and BK _Ca Channels in Smooth Muscle

AMPK Dilates Resistance Arteries via Activation of SERCA and BK _Ca Channels in Smooth Muscle

Physiological cyclic strain promotes endothelial cell survival via the induction of heme oxygenase-1

New synthetic AICAR derivatives with enhanced AMPK and ACC activation

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Activation of AMP-Activated Protein Kinase Inhibits the Proliferation of Human Endothelial Cells

Cited by 42 publications

References 52 publications

AMPK Dilates Resistance Arteries via Activation of SERCA and BK Ca Channels in Smooth Muscle

AMPK Dilates Resistance Arteries via Activation of SERCA and BK Ca Channels in Smooth Muscle

Physiological cyclic strain promotes endothelial cell survival via the induction of heme oxygenase-1

New synthetic AICAR derivatives with enhanced AMPK and ACC activation

Contact Info

Product

Resources

About

AMPK Dilates Resistance Arteries via Activation of SERCA and BK _Ca Channels in Smooth Muscle

AMPK Dilates Resistance Arteries via Activation of SERCA and BK _Ca Channels in Smooth Muscle