• Journal of Life Science
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• v.21 no.5
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• pp.621-626
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• 2011

AMP-activated protein kinase (AMPK), a heterotrimeric complex comprising a catalytic ${\alpha}$ subunit and regulatory ${\beta}$ and ${\gamma}$ subunits, has been primarily studied as a major metabolic regulator in various organisms, but recent genetic studies discover its novel physiological functions. The first animal model with no functional AMPK ${\gamma}$ subunit gene was generated by using Drosophila genetics. AMPK ${\gamma}$ flies demonstrated lethality with severe defects in cuticle formation. Further histological analysis found that deletion of AMPK ${\gamma}$ causes severe defects in cell polarity in embryo epithelia. The phosphorylation of nonmuscle myosin regulatory light chain (MRLC), a critical regulator of epithelial cell polarity, was also diminished in AMPK ${\gamma}$ embryo epithelia. These defects in AMPK ${\gamma}$ mutant epithelia were successfully restored by over-expression of AMPK ${\gamma}$. Collectively, these results suggested that AMPK ${\gamma}$ is a critical cell polarity regulator in metazoan development.

• Tuberculosis and Respiratory Diseases
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• v.78 no.1
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• pp.8-17
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• 2015

Background: AMP-activated protein kinase (AMPK) not only functions as an intracellular energy sensor and regulator, but is also a general sensor of oxidative stress. Furthermore, there is recent evidence that it participates in limiting acute inflammatory reactions, apoptosis and cellular senescence. Thus, it may oppose the development of chronic obstructive pulmonary disease. Methods: To investigate the role of AMPK in cigarette smoke-induced lung inflammation and emphysema we first compared cigarette smoking and polyinosinic-polycytidylic acid [poly(I:C)]-induced lung inflammation and emphysema in $AMPK{\alpha}1$-deficient ($AMPK{\alpha}1$-HT) mice and wild-type mice of the same genetic background. We then investigated the role of AMPK in the induction of interleukin-8 (IL-8) by cigarette smoke extract (CSE) in A549 cells. Results: Cigarette smoking and poly(I:C)-induced lung inflammation and emphysema were elevated in $AMPK{\alpha}1$-HT compared to wild-type mice. CSE increased AMPK activation in a CSE concentration- and time-dependent manner. 5-Aminoimidazole-4-carboxamide-1-${\beta}$-4-ribofuranoside (AICAR), an AMPK activator, decreased CSE-induced IL-8 production while Compound C, an AMPK inhibitor, increased it, as did pretreatment with an $AMPK{\alpha}1$-specific small interfering RNA. Conclusion: $AMPK{\alpha}1$-deficient mice have increased susceptibility to lung inflammation and emphysema when exposed to cigarette smoke, and AMPK appears to reduce lung inflammation and emphysema by lowering IL-8 production.

• Biomedical Science Letters
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• v.17 no.4
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• pp.273-281
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• 2011

Our previous study demonstrated that the Korean traditional medicine Gyeongshingangjeehwan (GGEx) inhibits obesity and insulin resistance in obese type 2 diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats. We investigated whether GGEx may affect AMP-activated protein kinase ${\alpha}$ ($AMPK{\alpha}$) since $AMPK{\alpha}$ activation is known to stimulate fatty acid oxidation in skeletal muscle of obese rodents. After OLETF rats were treated with GGEx, we studied the effects of GGEx on $AMPK{\alpha}$ and acetyl-CoA carboxylase (ACC) phosphorylation, and the expression of $AMPK{\alpha}$, $PPAR{\alpha}$, and $PPAR{\alpha}$ target genes. The effects of GGEx on mRNA expression of the above genes were also measured in C2C12 skeletal muscle cells. Administration of GGEx to OLETF rats for 8 weeks increased phosphorylation of $AMPK{\alpha}$ and ACC in skeletal muscle. GGEx also elevated skeletal muscle mRNA levels of $AMPK{\alpha}1$ and $AMPK{\alpha}2$ as well as $PPAR{\alpha}$ and its target genes. Consistent with the in vivo data, similar activation of genes was observed in GGEx-treated C2C12 cells. These results suggest that GGEx stimulates skeletal muscle $AMPK{\alpha}$ and $PPAR{\alpha}$ activation, leading to alleviation of obesity and related disorders.

• Journal of Yeungnam Medical Science
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• v.29 no.2
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• pp.77-82
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• 2012

AMP-activated protein kinase (AMPK) is an important cellular fuel sensor. Its activation requires phosphorylation at Thr-172, which resides in the activation loop of the ${\alpha}1$ and ${\alpha}2$ subunits. Several AMPK upstream kinases are capable of phosphorylating AMPK at Thr-172, including LKB1 and CaMKK${\beta}$ ($Ca^{2+}$/calmodulin-dependent protein kinase kinase${\beta}$). AMPK has been implicated in the regulation of physiological signals, such as in the inhibition of cholesterol fatty acid, and protein synthesis, and enhancement of glucose uptake and blood flow. AMPK activation also exhibits several salutary effects on the vascular function and improves vascular abnormalities. AMPK is modulated by numerous hormones and cytokines that regulate the energy balance in the whole body. These hormone and cytokines include leptin, adiponectin, ghrelin, and even thyroid hormones. Moreover, AMPK is activated by several drugs and xenobiotics. Some of these are in being clinically used to treat type 2 diabetes (e.g., metformin and thiazolidinediones), hypertension (e.g., nifedipine and losartan), and impaired blood flow (e.g., aspirin, statins, and cilostazol). I reviewed the precise mechanisms of the AMPK activation pathway and AMPK-modulating drugs.

• Natural Product Sciences
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• v.19 no.1
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• pp.1-7
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• 2013

AMP-activated protein kinase (AMPK) is a major cellular energy sensor and master regulator of metabolic homeostasis. On activation, this cellular fuel sensing enzyme induces a series of metabolic changes to balance energy consumption via multiple downstream signaling pathways controlling nutrient uptake and energy metabolism. This pivotal role of AMPK has led to the development of numerous AMPK activators which might be used as novel drug candidates in the treatment of AMPK related disorders, diabetes, obesity, and other metabolic diseases. Consequently, a number of patents have been published on AMPK activators from natural products and other sources. This review covers the patented AMPK activators from natural products and their therapeutic potential in treatment or prevention of metabolic diseases including diabetes and obesity.

• The Korean Journal of Physiology and Pharmacology
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• v.20 no.4
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• pp.325-332
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• 2016

Resveratrol, a phytoalexin, is reported to activate AMP-activated protein kinase (AMPK) in vascular cells. The blood-brain barrier (BBB), formed by specialized brain endothelial cells that are interconnected by tight junctions, strictly regulates paracellular permeability to maintain an optimal extracellular environment for brain homeostasis. The aim of this study was to elucidate the effects of resveratrol and the role of AMPK in BBB dysfunction induced by lipopolysaccharide (LPS). Exposure of human brain microvascular endothelial cells (HBMECs) to LPS ($1{\mu}g/ml$) for 4 to 24 hours week dramatically increased the permeability of the BBB in parallel with lowered expression levels of occluding and claudin-5, which are essential to maintain tight junctions in HBMECs. In addition, LPS significantly increased the reactive oxygen species (ROS) productions. All effects induced by LPS in HBVMCs were reversed by adenoviral overexpression of superoxide dismutase, inhibition of NAD(P) H oxidase by apocynin or gain-function of AMPK by adenoviral overexpression of constitutively active mutant (AMPK-CA) or by resveratrol. Finally, upregulation of AMPK by either AMPK-CA or resveratrol abolished the levels of LPS-enhanced NAD(P)H oxidase subunits protein expressions. We conclude that AMPK activation by resveratrol improves the integrity of the BBB disrupted by LPS through suppressing the induction of NAD(P)H oxidase-derived ROS in HBMECs.

• Asian-Australasian Journal of Animal Sciences
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• v.25 no.9
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• pp.1300-1308
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• 2012

The 5'-adenosine monophosphate-activated protein kinase (AMPK) is a key part of a kinase-signaling cascade that acts to maintain energy homeostasis. The objective of this experiment was to investigate the possible effects of fasting and refeeding on the gene expression of hypothalamic AMPK, some appetitive regulating peptides and lipid metabolism related enzymes. Seven-day-old male broiler (Arbor Acres) chicks were allocated into three equal treatments: fed ad libitum (control); fasted for 24 h; fasted for 24 h and then refed for 24 h. Compared with the control, the hypothalamic gene expression of $AMPK{\alpha}2$, $AMPK{\beta}1$, $AMPK{\beta}2$, $AMPK{\gamma}1$, Ste20-related adaptor protein ${\beta}$ ($STRAD{\beta}$), mouse protein $25{\alpha}$ ($MO25{\alpha}$) and agouti-related peptide (AgRP) were increased after fasting for 24 h. No significant difference among treatments was observed in mRNA levels of $AMPK{\alpha}1$, $AMPK{\gamma}2$, LKB1 and neuropeptide Y (NPY). However, the expression of $MO25{\beta}$, pro-opiomelanocortin (POMC), corticotropin-releasing hormone (CRH), ghrelin, fatty acid synthase (FAS), acetyl-CoA carboxylase ${\alpha}$ ($ACC{\alpha}$), carnitine palmitoyltransferase 1 (CPT-1) and sterol regulatory element binding protein-1 (SREBP-1) were significantly decreased. The present results indicated that 24 h fasting altered gene expression of AMPK subunits, appetite regulation peptides and lipometabolism related factors in chick's hypothalamus; the hypothalamic FAS signaling pathway might be involved in the AMPK regulated energy homeostasis and/or appetite regulation in poultry.

• Korean Journal of Exercise Nutrition
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• v.16 no.1
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• pp.35-41
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• 2012

We investigated the role of fatty acid availability on skeletal muscle AMPK activity and adenine nucleotide content. To investigate the chronic effects of elevated fatty acid in vivo Sprague-Dawley rats were fed a chow diet (15% fat) or a diet high in saturated (SAFA, 52% fat) or polyunsaturated (PUFA, 52% fat) fat for eight weeks. High fat diets increased (P < 0.05) plasma FFA levels by 25%. AMPK activity was increased in SAFA and PUFA rats and occurred in the absence of changes in ATP, AMP, phosphocreatine and glycogen content. These results suggest that increasing fatty acid availability increases AMPK activity independent of changes in the cellular energy charge, and implicate the regulation of AMPK by a covalent mechanism. These data also support the contention that increasing fatty acid availability can increase subsequent fatty acid oxidation by an AMPK-mediated process.

• Biomolecules & Therapeutics
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• v.32 no.2
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• pp.171-182
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• 2024

All cells are equipped with intricate signaling networks to meet the energy demands and respond to the nutrient availability in the body. AMP-activated protein kinase (AMPK) is among the most potent regulators of cellular energy balance. Under ATP -deprived conditions, AMPK phosphorylates substrates and affects various biological processes, such as lipid/glucose metabolism and protein synthesis. These actions further affect the cell growth, death, and functions, altering the cellular outcomes in energy-restricted environments. AMPK plays vital roles in maintaining good health. AMPK dysfunction is observed in various chronic diseases, making it a promising target for preventing and alleviating such diseases. Herein, we highlight the different AMPK functions, especially in allergy, aging, and cancer, to facilitate the development of new therapeutic approaches in the future.

• The Korean Journal of Physiology and Pharmacology
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• v.17 no.4
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• pp.331-338
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• 2013

AMP-activated protein kinase (AMPK), an important regulator of energy metabolism, is activated in response to cellular stress when intracellular levels of AMP increase. We investigated the neuroprotective effects of AMPK against scopolamine-induced memory impairment in vivo and glutamate-induced cytotoxicity in vitro. An adenovirus expressing AMPK wild type alpha subunit (WT) or a dominant negative form (DN) was injected into the hippocampus of rats using a stereotaxic apparatus. The AMPK WT-injected rats showed significant reversal of the scopolamine induced cognitive deficit as evaluated by escape latency in the Morris water maze. In addition, they showed enhanced acetylcholinesterase (AChE)-reactive neurons in the hippocampus, implying increased cholinergic activity in response to AMPK. We also studied the cellular mechanism by which AMPK protects against glutamate-induced cell death in primary cultured rat hippocampal neurons. We further demonstrated that AMPK WT-infected cells increased cell viability and reduced Annexin V positive hippocampal neurons. Western blot analysis indicated that AMPK WT-infected cells reduced the expression of Bax and had no effects on Bcl-2, which resulted in a decreased Bax/Bcl-2 ratio. These data suggest that AMPK is a useful cognitive impairment treatment target, and that its beneficial effects are mediated via the protective capacity of hippocampal neurons.