scholarly journals Pentamethylquercetin generates beneficial effects in monosodium glutamate-induced obese mice and C2C12 myotubes by activating AMP-activated protein kinase

Diabetologia ◽  
2012 ◽  
Vol 55 (6) ◽  
pp. 1836-1846 ◽  
Author(s):  
J. Z. Shen ◽  
L. N. Ma ◽  
Y. Han ◽  
J. X. Liu ◽  
W. Q. Yang ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Monosodium Glutamate ◽  
C2c12 Myotubes ◽  
Obese Mice ◽  
Beneficial Effects ◽  
Amp Activated Protein Kinase

scholarly journals AMP-activated protein kinase pathway: a potential therapeutic target in cardiometabolic disease

2009 ◽  
Vol 116 (8) ◽  
pp. 607-620 ◽  
Author(s):  
Aaron K. F. Wong ◽  
Jacqueline Howie ◽  
John R. Petrie ◽  
Chim C. Lang
Keyword(s):  
Protein Kinase ◽  
Metabolic Diseases ◽  
Elongation Factor ◽  
Cardiometabolic Disease ◽  
Acid Oxidation ◽  
Ampk Activation ◽  
Atp Production ◽  
Beneficial Effects ◽  
Eukaryotic Elongation Factor ◽  
Amp Activated Protein Kinase

AMPK (AMP-activated protein kinase) is a heterotrimetric enzyme that is expressed in many tissues, including the heart and vasculature, and plays a central role in the regulation of energy homoeostasis. It is activated in response to stresses that lead to an increase in the cellular AMP/ATP ratio caused either by inhibition of ATP production (i.e. anoxia or ischaemia) or by accelerating ATP consumption (i.e. muscle contraction or fasting). In the heart, AMPK activity increases during ischaemia and functions to sustain ATP, cardiac function and myocardial viability. There is increasing evidence that AMPK is implicated in the pathophysiology of cardiovascular and metabolic diseases. A principle mode of AMPK activation is phosphorylation by upstream kinases [e.g. LKB1 and CaMK (Ca2+/calmodulin-dependent protein kinase], which leads to direct effects on tissues and phosphorylation of various downstream kinases [e.g. eEF2 (eukaryotic elongation factor 2) kinase and p70 S6 kinase]. These upstream and downstream kinases of AMPK have fundamental roles in glucose metabolism, fatty acid oxidation, protein synthesis and tumour suppression; consequently, they have been implicated in cardiac ischaemia, arrhythmias and hypertrophy. Recent mechanistic studies have shown that AMPK has an important role in the mechanism of action of MF (metformin), TDZs (thiazolinediones) and statins. Increased understanding of the beneficial effects of AMPK activation provides the rationale for targeting AMPK in the development of new therapeutic strategies for cardiometabolic disease.

scholarly journals Lewis lung carcinoma regulation of mechanical stretch-induced protein synthesis in cultured myotubes

2016 ◽  
Vol 310 (1) ◽  
pp. C66-C79 ◽  
Author(s):  
Song Gao ◽  
James A. Carson
Keyword(s):  
Protein Synthesis ◽  
Protein Kinase ◽  
Lung Carcinoma ◽  
Lewis Lung Carcinoma ◽  
Mammalian Target Of Rapamycin ◽  
Mechanical Stretch ◽  
C2c12 Myotubes ◽  
Lewis Lung ◽  
Mtorc1 Signaling ◽  
Amp Activated Protein Kinase

Mechanical stretch can activate muscle and myotube protein synthesis through mammalian target of rapamycin complex 1 (mTORC1) signaling. While it has been established that tumor-derived cachectic factors can induce myotube wasting, the effect of this catabolic environment on myotube mechanical signaling has not been determined. We investigated whether media containing cachectic factors derived from Lewis lung carcinoma (LLC) can regulate the stretch induction of myotube protein synthesis. C2C12 myotubes preincubated in control or LLC-derived media were chronically stretched. Protein synthesis regulation by anabolic and catabolic signaling was then examined. In the control condition, stretch increased mTORC1 activity and protein synthesis. The LLC treatment decreased basal mTORC1 activity and protein synthesis and attenuated the stretch induction of protein synthesis. LLC media increased STAT3 and AMP-activated protein kinase phosphorylation in myotubes, independent of stretch. Both stretch and LLC independently increased ERK1/2, p38, and NF-κB phosphorylation. In LLC-treated myotubes, the inhibition of ERK1/2 and p38 rescued the stretch induction of protein synthesis. Interestingly, either leukemia inhibitory factor or glycoprotein 130 antibody administration caused further inhibition of mTORC1 signaling and protein synthesis in stretched myotubes. AMP-activated protein kinase inhibition increased basal mTORC1 signaling activity and protein synthesis in LLC-treated myotubes, but did not restore the stretch induction of protein synthesis. These results demonstrate that LLC-derived cachectic factors can dissociate stretch-induced signaling from protein synthesis through ERK1/2 and p38 signaling, and that glycoprotein 130 signaling is associated with the basal stretch response in myotubes.

scholarly journals Calorie Restriction: Is AMPK a Key Sensor and Effector?

Physiology ◽  
2011 ◽  
Vol 26 (4) ◽  
pp. 214-224 ◽  
Author(s):  
Carles Cantó ◽  
Johan Auwerx
Keyword(s):  
Protein Kinase ◽  
Life Span ◽  
Calorie Restriction ◽  
Energy Availability ◽  
Beneficial Effects ◽  
Extend Life Span ◽  
Energy Sensor ◽  
External Cues ◽  
Amp Activated Protein Kinase

Dietary restriction can extend life span in most organisms tested to date, suggesting that mechanisms sensing nutrient and energy availability might regulate longevity. The AMP-activated protein kinase (AMPK) has emerged as a key energy sensor with the ability to transcriptionally reprogram the cell and metabolically adapt to external cues. In this review, we will discuss the possible role of AMPK in the beneficial effects of calorie restriction on health and life span.

scholarly journals StimulatingS-adenosyl-l-methionine synthesis extends lifespan via activation of AMPK

2016 ◽  
Vol 113 (42) ◽  
pp. 11913-11918 ◽  
Author(s):  
Takafumi Ogawa ◽  
Ryohei Tsubakiyama ◽  
Muneyoshi Kanai ◽  
Tetsuya Koyama ◽  
Tsutomu Fujii ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Protein Kinase ◽  
Cell Survival ◽  
Metabolic Effects ◽  
Model Organisms ◽  
Lifespan Extension ◽  
Beneficial Effects ◽  
Energy Sensing ◽  
Amp Activated Protein Kinase ◽  
Methionine Synthesis

Dietary restriction (DR), such as calorie restriction (CR) or methionine (Met) restriction, extends the lifespan of diverse model organisms. Although studies have identified several metabolites that contribute to the beneficial effects of DR, the molecular mechanism underlying the key metabolites responsible for DR regimens is not fully understood. Here we show that stimulatingS-adenosyl-l-methionine (AdoMet) synthesis extended the lifespan of the budding yeastSaccharomyces cerevisiae. The AdoMet synthesis-mediated beneficial metabolic effects, which resulted from consuming both Met and ATP, mimicked CR. Indeed, stimulating AdoMet synthesis activated the universal energy-sensing regulator Snf1, which is theS. cerevisiaeortholog of AMP-activated protein kinase (AMPK), resulting in lifespan extension. Furthermore, our findings revealed thatS-adenosyl-l-homocysteine contributed to longevity with a higher accumulation of AdoMet only under the severe CR (0.05% glucose) conditions. Thus, our data uncovered molecular links between Met metabolites and lifespan, suggesting a unique function of AdoMet as a reservoir of Met and ATP for cell survival.

scholarly journals Antiobesity Effect ofAstilbe chinensisFranch. et Savet. Extract through Regulation of Adipogenesis and AMP-Activated Protein Kinase Pathways in 3T3-L1 Adipocyte and High-Fat Diet-Induced C57BL/6N Obese Mice

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Xian Hua Zhang ◽  
Zhiqiang Wang ◽  
Bueom-Goo Kang ◽  
Seung Hwan Hwang ◽  
Jae-Young Lee ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Lipid Content ◽  
High Fat Diet ◽  
Binding Protein ◽  
Resistance Index ◽  
Nonesterified Fatty Acid ◽  
Dependent Manner ◽  
Obese Mice ◽  
High Fat ◽  
Amp Activated Protein Kinase

Astilbe chinensisFranch. et Savat. (AC) has been used in traditional medicine for the treatment of chronic bronchitis, arthralgia, and gastralgia. In this study, we investigated the antiobesity effect of AC extract on 3T3-L1 preadipocytes and high-fat-diet-fed C57BL/6N obese mice. We found that AC extracts dramatically decreased the lipid content of 3T3-L1 cells in a concentration-dependent manner without cytotoxicity. The action mechanism of AC extract was demonstrated to be the inhibition of lipid accumulation and dose-dependent decrease in the expression of CCAAT/enhancer-binding proteinα(C/EBPα), peroxisome proliferator-activated receptor-γ(PPAR-γ), and sterol regulatory element-binding protein 1 (SREBP1). Furthermore, AC extract increased the mitochondrial phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC), mitochondrial biogenesis, and lipolysis-related factors. In amice model of high-fat-diet-induced obesity, the mice administered AC extract experienced significant decrease of 64% in weight gain, 55% in insulin resistance index, 22% in plasma triglycerides (TG), 56% in total cholesterol (TC), and 21% in nonesterified fatty acid (NEFA) levels compared with those in the high-fat diet-fed control mice. Collectively, these results indicated that AC extract exerted antiobesogenic activity through the modulation of the AMPK signaling pathway, inhibition of adipogenesis, decreased lipid content, and reduced adipocyte size.

scholarly journals Eicosapentaenoic Acid (EPA) Modulates Glucose Metabolism by Targeting AMP-Activated Protein Kinase (AMPK) Pathway

2019 ◽  
Vol 20 (19) ◽  
pp. 4751 ◽  
Author(s):  
Nami Kim ◽  
Mi Sun Kang ◽  
Miso Nam ◽  
Shin Ae Kim ◽  
Geum-Sook Hwang ◽  
...  
Keyword(s):  
Protein Kinase ◽  
P38 Mapk ◽  
Molecular Mechanisms ◽  
Glucose Transporter ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Omega 3 ◽  
Beneficial Effects ◽  
Calcium Calmodulin Dependent ◽  
Amp Activated Protein Kinase

EPA, an omega-3 polyunsaturated fatty acid, exerts beneficial effects on human health. However, the molecular mechanisms underlying EPA function are poorly understood. The object was to illuminate molecular mechanism underlying EPA’s role. Here, 1H-NMR-based metabolic analysis showed enhanced branched-chain amino acids (BCAAs) and lactate following EPA treatment in skeletal muscle cells. EPA regulated mitochondrial oxygen consumption rate. Furthermore, EPA induced calcium/calmodulin-dependent protein kinase kinase (CaMKK) through the generation of intracellular calcium. This induced the phosphorylation of AMP-activated protein kinase (AMPK) and p38 mitogen-activated protein kinase (p38 MAPK) that led to glucose uptake, and the translocation of glucose transporter type 4 (GLUT4) in muscles. In conclusion, EPA exerts benign effects on glucose through the activation of AMPK-p38 MAPK signaling pathways in skeletal muscles.

scholarly journals APPL1 Mediates Adiponectin-Induced LKB1 Cytosolic Localization Through the PP2A-PKCζ Signaling Pathway

2011 ◽  
Vol 25 (10) ◽  
pp. 1773-1785 ◽  
Author(s):  
Sathyaseelan S. Deepa ◽  
Lijun Zhou ◽  
Jiyoon Ryu ◽  
Changhua Wang ◽  
Xuming Mao ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Leucine Zipper ◽  
Molecular Mechanisms ◽  
Adaptor Protein ◽  
C2c12 Myotubes ◽  
Pleckstrin Homology Domain ◽  
Phosphatase 2A ◽  
Ampk Activity ◽  
Amp Activated Protein Kinase ◽  
Phosphotyrosine Binding Domain

We recently found that the adaptor protein containing pleckstrin homology domain, phosphotyrosine binding domain and leucine zipper motif (APPL)1 is essential for mediating adiponectin signal to induce liver kinase B (LKB)1 cytosloic translocation, an essential step for activation of AMP-activated protein kinase (AMPK) in cells. However, the underlying molecular mechanisms remain unknown. Here, we demonstrate that treating C2C12 myotubes with adiponectin promoted APPL1 interaction with protein phosphatase 2A (PP2A) and protein kinase Cζ (PKCζ), leading to the activation of PP2A and subsequent dephosphorylation and inactivation of PKCζ. The adiponectin-induced inactivation of PKCζ results in dephosphorylation of LKB1 at Ser307 and its subsequent translocation to the cytosol, where it stimulates AMPK activity. Interestingly, we found that metformin also induces LKB1 cytosolic translocation, but the stimulation is independent of APPL1 and the PP2A-PKCζ pathway. Together, our study uncovers a new mechanism underlying adiponectin-stimulated AMPK activation in muscle cells and shed light on potential targets for prevention and treatment of insulin resistance and its associated diseases.

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