Abstract 5559: Role of AMP-activated Protein Kinase in Ischemia-Reperfusion-Induced Barrier Failure in Endothelial Monolayers

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Muhammad Assad ◽  
Muhammad Arshad ◽  
Frauke V Haertel ◽  
Muhammad Aslam ◽  
Ingrid Fleming ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Barrier Function ◽  
Ischemia Reperfusion ◽  
Fold Increase ◽  
Gap Formation ◽  
Endothelial Monolayers ◽  
Ampk Phosphorylation ◽  
Barrier Failure ◽  
Amp Activated Protein Kinase

Background: Ischemia-reperfusion provokes endothelial barrier dysfunction leading to edema formation and organ failure. The AMP-activated protein kinase (AMPK) is a fuel sensor which becomes activated under ischemia. It is now apparent that AMPK may also play important roles in stabilization of cell-adhesion. Here, it is hypothesized that AMPK may play an important role in protection barrier function under metabolic stress. Methods and Results: Overexpression of a dominant negative AMPK mutant in endothelial monolayers from human umbilical veins (EC) caused a 2-fold increase in basal permeability (albumin flux across the monolayers). In accordance, downregulation of AMPK by siRNA (~60%) leads to gap formation between adjacent EC, disintegration of cell adhesion structures and alterations of the cytoskeleton (loss of VE-cadherin at cell borders, actin stress fiber formation; immunocytochemistry), indicating that AMPK plays an important role in maintenance of barrier integrity. To analyse the role of AMPK on barrier function EC were exposed to ischemia (40 min, Po 2 <5 mm Hg; pH 6.4) followed by reperfusion (40 min, Po 2 =140 mm Hg; pH 7.4). Ischemia caused an immediate increase in permeability (gap formation, video-imaging technique) and a 3-fold increase in AMPK activity (AMPK phosphorylation; western blot) after 40 min. During reperfusion gap formation was further increased by 307± 9 % (P<0.05, n=5) within the ongoing 40 min. In contrast, AMPK phosphorylation rapidly declined to basal level within the first 10 minutes of reperfusion. However, addition of AICAR (AMPK activator; 5-aminoimidizole-4-carboxamide riboside), at the onset of reperfusion caused a rapid increase in AMPK phosphorylation and abolished the reperfusion-induced gap formation. Pretreatment of the cells with AICAR before the onset of ischemia reduced reperfusion-induced gap formation by 50 %. Conclusion: AMPK is involved in maintenance of cell-cell contacts and stabilization of basal barrier function. Pharmacological activation of AMPK within the first minutes of reperfusion can prevent hyperpermeability induced by reperfusion stress. Hence, activation of AMPK may provide a new therapeutic option to prevent ischemia-reperfusion barrier failure.

Simulated microgravity increases myocardial susceptibility to ischemia–reperfusion injury via a deficiency of AMP-activated protein kinase

2017 ◽  
Vol 95 (1) ◽  
pp. 59-71 ◽  
Author(s):  
Yuan-Ming Lu ◽  
Bo Jiao ◽  
Jun Lee ◽  
Lin Zhang ◽  
Zhi-Bin Yu
Keyword(s):  
Protein Kinase ◽  
Infarct Size ◽  
Simulated Microgravity ◽  
Ischemia Reperfusion Injury ◽  
Diastolic Pressure ◽  
Ischemia Reperfusion ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Ampk Phosphorylation ◽  
Amp Activated Protein Kinase

Gravitation is an important factor in maintaining cardiac contractility. Our study investigated whether simulated microgravity increases myocardial susceptibility to ischemia–reperfusion (IR) injury. Using the Langendorff-perfused heart model with 300 beats/min pacing, 4-week tail suspension (SUS) and control (CON) male Sprague-Dawley rats (n = 10 rats/group) were subjected to 60 min of left anterior descending coronary artery (LAD) occlusion followed by 120 min of reperfusion. Left ventricular end-systolic pressure (LVESP), left ventricular end-diastolic pressure (LVEDP), creatine kinase (CK) and lactate dehydrogenase (LDH) activity, and infarct size were assessed. Data demonstrated that there were significantly increased LVEDP, CK, LDH, and infarct size in SUS compared with CON (P < 0.05), accompanied by decreased LVESP (P < 0.05). Furthermore, TUNEL-positive cardiomyocytes were higher in SUS than that in CON (P < 0.01), and AMP-activated protein kinase (AMPK) phosphorylation and Bcl-2/Bax in SUS were less compared with CON (P < 0.05). Similarly, isolated hearts pre-treated with A-769662 exhibited better recovery of cardiac function, increased AMPK phosphorylation, and reduced necrosis and apoptosis. Furthermore, AMPKα protein showed a significant suppression in 4-week hindlimb unweighting rats. These results suggest that AMPK deficiency increases myocardial susceptibility to IR injury in rats subjected to simulated microgravity.

scholarly journals The role of AMP-activated protein kinase in quercetin-induced apoptosis of HL-60 cells

2014 ◽  
Vol 46 (5) ◽  
pp. 394-400 ◽  
Author(s):  
J. Xiao ◽  
G. Niu ◽  
S. Yin ◽  
S. Xie ◽  
Y. Li ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Induced Apoptosis ◽  
Amp Activated Protein Kinase

Role of the AMP-activated protein kinase in regulating fatty acid metabolism during exerciseThis paper is one of a selection of papers published in this Special Issue, entitled 14th International Biochemistry of Exercise Conference – Muscles as Molecular and Metabolic Machines, and has undergone the Journal’s usual peer review process.

2009 ◽  
Vol 34 (3) ◽  
pp. 315-322 ◽  
Author(s):  
Gregory R. Steinberg
Keyword(s):  
Skeletal Muscle ◽  
Fatty Acids ◽  
Adipose Tissue ◽  
Fatty Acid ◽  
Protein Kinase ◽  
Fatty Acid Metabolism ◽  
Acid Metabolism ◽  
Moderate Intensity ◽  
Amp Activated Protein Kinase

During moderate-intensity exercise, fatty acids are the predominant substrate for working skeletal muscle. The release of fatty acids from adipose tissue stores, combined with the ability of skeletal muscle to actively fine tune the gradient between fatty acid and carbohydrate metabolism, depending on substrate availability and energetic demands, requires a coordinated system of metabolic control. Over the past decade, since the discovery that AMP-activated protein kinase (AMPK) was increased in accordance with exercise intensity, there has been significant interest in the proposed role of this ancient stress-sensing kinase as a critical integrative switch controlling metabolic responses during exercise. In this review, studies examining the role of AMPK as a regulator of fatty acid metabolism in both adipose tissue and skeletal muscle during exercise will be discussed. Exercise induces activation of AMPK in adipocytes and regulates triglyceride hydrolysis and esterfication through phosphorylation of hormone sensitive lipase (HSL) and glycerol-3-phosphate acyl-transferase, respectively. In skeletal muscle, exercise-induced activation of AMPK is associated with increases in fatty acid uptake, phosphorylation of HSL, and increased fatty acid oxidation, which is thought to occur via the acetyl-CoA carboxylase-malony-CoA-CPT-1 signalling axis. Despite the importance of AMPK in regulating fatty acid metabolism under resting conditions, recent evidence from transgenic models of AMPK deficiency suggest that alternative signalling pathways may also be important for the control of fatty acid metabolism during exercise.

AMPK activation with AICAR provokes an acute fall in plasma [K+]

2008 ◽  
Vol 294 (1) ◽  
pp. C126-C135 ◽  
Author(s):  
Dan Zheng ◽  
Anjana Perianayagam ◽  
Donna H. Lee ◽  
M. Douglas Brannan ◽  
Li E. Yang ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Infusion Rate ◽  
Extracellular Fluid ◽  
Ampk Activation ◽  
Conscious Rats ◽  
Significant Fall ◽  
Ampk Phosphorylation ◽  
Atp Levels ◽  
Ampk Activity ◽  
Amp Activated Protein Kinase

AMP-activated protein kinase (AMPK), activated by an increase in intracellular AMP-to-ATP ratio, stimulates pathways that can restore ATP levels. We tested the hypothesis that AMPK activation influences extracellular fluid (ECF) K+ homeostasis. In conscious rats, AMPK was activated with 5-aminoimidazole-4-carboxamide-1-beta-d-ribofuranoside (AICAR) infusion: 38.4 mg/kg bolus then 4 mg·kg−1·min−1 infusion. Plasma [K+] and [glucose] both dropped at 1 h of AICAR infusion and [K+] dropped to 3.3 ± 0.04 mM by 3 h, linearly related to the increase in muscle AMPK phosphorylation. AICAR treatment did not increase urinary K+ excretion. AICAR lowered [K+] whether plasma [K+] was chronically elevated or lowered. The K+ infusion rate needed to maintain baseline plasma [K+] reached 15.7 ± 1.3 μmol K+·kg−1·min−1 between 120 and 180 min AICAR infusion. In mice expressing a dominant inhibitory form of AMPK in the muscle (Tg-KD1), baseline [K+] was not different from controls (4.2 ± 0.1 mM), but the fall in plasma [K+] in response to AICAR (0.25 g/kg) was blunted: [K+] fell to 3.6 ± 0.1 in controls and to 3.9 ± 0.1 mM in Tg-KD1, suggesting that ECF K+ redistributes, at least in part, to muscle ICF. In summary, these findings illustrate that activation of AMPK activity with AICAR provokes a significant fall in plasma [K+] and suggest a novel mechanism for redistributing K+ from ECF to ICF.

The emerging role of AMP-activated protein kinase in cholestatic liver diseases

2017 ◽  
Vol 125 ◽  
pp. 105-113 ◽  
Author(s):  
Xiaojiaoyang Li ◽  
Runping Liu ◽  
Luyong Zhang ◽  
Zhenzhou Jiang
Keyword(s):  
Protein Kinase ◽  
Liver Diseases ◽  
Amp Activated Protein Kinase
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