AMP-activated protein kinase (AMPK) is a crucial cellular energy sensor. Once activated by falling energy status, it promotes ATP production by increasing the activity or expression of proteins involved in catabolism while conserving ATP by switching off biosynthetic pathways. AMPK also regulates metabolic energy balance at the whole-body level. For example, it mediates the effects of agents acting on the hypothalamus that promote feeding and entrains circadian rhythms of metabolism and feeding behaviour. Finally, recent studies reveal that AMPK conserves ATP levels through the regulation of processes other than metabolism, such as the cell cycle and neuronal membrane excitability.
"However, only AMPKα has been demonstrated in the endometria of women with PCOS and endometrial cancer  . Furthermore, while hormonal, nutrient, and metabolic stress signals regulate AMPK activation and its activity in multiple peripheral tissues such as liver, skeletal muscle, and adipose tissues   as well as different cancer cells , to our knowledge no studies have investigated any causality between androgen , AR expression, and AMPK activation in the endometrium under physiological and pathological conditions. The aims of the present study, therefore, were to investigate the temporal and spatial expression patterns of AR, p-AMPKα, AMPKα, and Ki67 (a cellular marker for proliferation) in the endometrium of PCOS patients in different phases of the menstrual cycle or with hyperplasia. "
[Show abstract][Hide abstract] ABSTRACT: The failure of reproductive success in polycystic ovary syndrome (PCOS) patients could be in part due to endometrial dysfunction. However, no studies have investigated any causality between androgen, androgen receptor (AR) expression, and adenosine monophosphate activated protein kinase (AMPK) activation in the endometrium under physiological and pathological conditions. In the present study, we show that 1) endometrial AR expression levels fluctuate in non-PCOS and PCOS patients during the menstrual cycle; 2) the menstrual phase-dependent alteration of p-AMPKα expression occurs in non-PCOS patients but not in PCOS patients; 3) AR expression is higher in PCOS patients than non-PCOS patients during hyperplasia while AMPKα activation (indicated by the ratio of p-AMPKα to AMPKα); and 4) co-localization of AR and Ki-67 in epithelial cell nuclei is observed in endometrial hyperplasia. Importantly, using in vitro human tissue culture and an in vivo 5α-dihydrotestosterone-treated rat model, we show that the action of androgen on AMPKα activation is likely mediated through nuclear AR, especially in epithelial cells. Collectively, we present evidence that AR expression and AMPKα activation depend on menstrual cycle phase and the presence of PCOS, and the data suggest that AR-mediated regulation of AMPKα activation might play a role in the development of endometrial hyperplasia.
International journal of biological sciences 10/2015; 11(1112):1376-1389. DOI:10.7150/ijbs.13109 · 4.51 Impact Factor
"However, the role of DEC1 in the metabolic process remains unclear. AMP-activated protein kinase (AMPK) is a serine/threonine protein kinase that activates the metabolic process in response to energy demands, such as exercise, heat shock and a low glucose level  . AMPK has three subunits, a, b and g; and the a-subunit plays a crucial role in catalytic activity  . "
[Show abstract][Hide abstract] ABSTRACT: Basic helix-loop-helix (bHLH) transcription factor DEC1 (bHLHE40/Stra13/Sharp2) is one of the clock genes that show a circadian rhythm in various tissues. AMP-activated protein kinase (AMPK) activity plays important roles in the metabolic process and in cell death induced by glucose depletion. Recent reports have shown that AMPK activity exhibited a circadian rhythm. However, little is known regarding the regulatory mechanisms involved in the circadian rhythm of AMPK activity. The aim of this study is to investigate whether there is a direct correlation between DEC1 expression and AMPK activity. DEC1 protein and AMPK activity showed a circadian rhythm in the mouse liver with different peak levels. Knocking down DEC1 expression increased AMPK activity, whereas overexpression of DEC1 decreased it. Overexpressing the DEC1 basic mutants had little effect on the AMPK activity. DEC1 bound to the E-box of the LKB1 promoter, decreased LKB1 activity and total protein levels. There was an inverse relationship between DEC1 expression and AMPK activity. Our results suggest that DEC1 negatively regulates AMPK activity via LKB1.
Biochemical and Biophysical Research Communications 10/2015; DOI:10.1016/j.bbrc.2015.10.077 · 2.30 Impact Factor
"switch from fermentative to oxidative metabolism in the absence of glucose (Hedbacker and Carlson, 2008), and AMPK regulates glucose, lipid, and protein metabolism, mitochondrial biogenesis, and feeding behavior in animals (Hardie et al., 2012). They are generally activated under energy starvation conditions and trigger metabolic reprograming to slow down energy-consuming processes and turn on pathways for alternative energy production in order to survive the stress conditions (Hardie, 2007; Tome et al., 2014). "
[Show abstract][Hide abstract] ABSTRACT: Metabolic adjustment to changing environmental conditions, particularly balancing of growth and defense responses, is crucial for all organisms to survive. The evolutionary conserved AMPK/Snf1/SnRK1 kinases are well-known metabolic master regulators in the low-energy response in animals, yeast and plants. They act at two different levels: by modulating the activity of key metabolic enzymes, and by massive transcriptional reprogramming. While the first part is well established, the latter function is only partially understood in animals and not at all in plants. Here we identified the Arabidopsis transcription factor bZIP63 as key regulator of the starvation response and direct target of the SnRK1 kinase. Phosphorylation of bZIP63 by SnRK1 changed its dimerization preference, thereby affecting target gene expression and ultimately primary metabolism. A bzip63 knock-out mutant exhibited starvation-related phenotypes, which could be functionally complemented by wild type bZIP63, but not by a version harboring point mutations in the identified SnRK1 target sites.
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