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AMP activated kinase

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https://www.readbyqxmd.com/read/29452207/glycogen-synthase-kinase-3%C3%AE-promotes-liver-innate-immune-activation-by-restraining-amp-activated-protein-kinase-activation
#1
Haoming Zhou, Han Wang, Ming Ni, Shi Yue, Yongxiang Xia, Ronald W Busuttil, Jerzy W Kupiec-Weglinski, Ling Lu, Xuehao Wang, Yuan Zhai
BACKGROUND & AIMS: Glycogen synthase kinase 3β (Gsk3β) is a ubiquitously expressed kinase with distinctive functions in different types of cells. Although its roles in regulating innate immune activation and ischemia and reperfusion injuries (IRI) have been well documented, underlying mechanisms remain ambiguous, due in part to the lack of cell-specific tools in vivo. METHODS: We created a myeloid-specific Gsk3β KO strain to study its function in macrophages in a murine liver partial warm ischemia model...
February 13, 2018: Journal of Hepatology
https://www.readbyqxmd.com/read/29452132/effect-of-the-gstm1-gene-deletion-on-glycemic-variability-sympatho-vagal-balance-and-arterial-stiffness-in-patients-with-metabolic-syndrome-but-without-diabetes
#2
Andrea Iorio, Dorina Ylli, Renato Polimanti, Fabiana Picconi, Paola Maggio, Davide Francomano, Antonio Aversa, Dario Manfellotto, Maria Fuciarelli, Simona Frontoni
AIMS: An increased rate of cerebrovascular complications in patients with metabolic syndrome (MetS) has been reported. Previous studies demonstrated an association between glycemic variability (GV) and cerebrovascular reactivity (CRV) in MetS, thus suggesting a putative role of GV on cerebrovascular events. Although the pathophysiological mechanism linking GV to damage is still to be elucidated, evidence suggests oxidative stress plays a crucial role. Since functional variants in glutathione S-transferases (GST) genes modulate the cellular detoxification processes, the aim of this study was to elucidate the involvement of GSTs in MetS and investigating the correlation with GV, arterial stiffness, and sympatho-vagal (SV) balance...
February 13, 2018: Diabetes Research and Clinical Practice
https://www.readbyqxmd.com/read/29451563/a-highly-sensitive-non-radioactive-activity-assay-for-amp-activated-protein-kinase-ampk
#3
Yan Yan, Xin Gu, H Eric Xu, Karsten Melcher
While many methods exist to quantitatively determine protein kinase activities, 32 P-based radioactive assays remain the workhorse of many laboratories due to their high sensitivity, high signal to noise ratio, lack of interference by fluorescent and light-absorbing small molecules, and easy quantitation. Here, we demonstrate that the interaction between the yeast Rad53 Forkhead-associated (FHA) domain and a peptide optimized for phosphorylation by AMP-Activated Protein Kinase (AMPK), which has previously been exploited for the generation of intracellular phosphorylation sensors, can serve as a readout for a highly sensitive two-step AMPK AlphaScreen kinase assay with exceptional signal-to-noise ratio...
March 2018: Methods Protoc
https://www.readbyqxmd.com/read/29449563/cinacalcet-mediated-activation-of-the-camkk%C3%AE-lkb1-ampk-pathway-attenuates-diabetic-nephropathy-in-db-db-mice-by-modulation-of-apoptosis-and-autophagy
#4
Ji Hee Lim, Hyung Wook Kim, Min Young Kim, Tae Woo Kim, Eun Nim Kim, Yaeni Kim, Sungjin Chung, Young Soo Kim, Bum Soon Choi, Yong-Soo Kim, Yoon Sik Chang, Hye Won Kim, Cheol Whee Park
Apoptosis and autophagy are harmoniously regulated biological processes for maintaining tissue homeostasis. AMP-activated protein kinase (AMPK) functions as a metabolic sensor to coordinate cellular survival and function in various organs, including the kidney. We investigated the renoprotective effects of cinacalcet in high-glucose treated human glomerular endothelial cells (HGECs), murine podocytes and C57BLKS/J-db/db mice. In cultured HGECs and podocytes, cinacalcet decreased oxidative stress and apoptosis and increased autophagy that were attributed to the increment of intracellular Ca 2+ concentration and the phosphorylation of Ca 2+ /calmodulin-dependent protein kinase kinaseβ (CaMKKβ)-Liver kinase B1 (LKB1)-AMPK and their downstream signals including the phosphorylation of endothelial nitric oxide synthase (eNOS) and increases in superoxide dismutases and B cell leukemia/lymphoma 2/BCL-2-associated X protein expression...
February 15, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29449364/diabetic-cardiomyopathy-an-update-of-mechanisms-contributing-to-this-clinical-entity
#5
REVIEW
Guanghong Jia, Michael A Hill, James R Sowers
Heart failure and related morbidity and mortality are increasing at an alarming rate, in large part, because of increases in aging, obesity, and diabetes mellitus. The clinical outcomes associated with heart failure are considerably worse for patients with diabetes mellitus than for those without diabetes mellitus. In people with diabetes mellitus, the presence of myocardial dysfunction in the absence of overt clinical coronary artery disease, valvular disease, and other conventional cardiovascular risk factors, such as hypertension and dyslipidemia, has led to the descriptive terminology, diabetic cardiomyopathy...
February 16, 2018: Circulation Research
https://www.readbyqxmd.com/read/29448247/knockdown-of-magea6-activates-amp-activated-protein-kinase-ampk-signaling-to-inhibit-human-renal-cell-carcinoma-cells
#6
Xueting Ye, Jing Xie, Hang Huang, Zhexian Deng
BACKGROUND/AIMS: Melanoma antigen A6 (MAGEA6) is a cancer-specific ubiquitin ligase of AMP-activated protein kinase (AMPK). The current study tested MAGEA6 expression and potential function in renal cell carcinoma (RCC). METHODS: MAGEA6 and AMPK expression in human RCC tissues and RCC cells were tested by Western blotting assay and qRT-PCR assay. shRNA method was applied to knockdown MAGEA6 in human RCC cells. Cell survival and proliferation were tested by MTT assay and BrdU ELISA assay, respectively...
February 9, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29448105/casein-kinase-2-phosphorylates-and-stabilizes-c-ebp%C3%AE-in-pancreatic-%C3%AE-cells
#7
Tomoko Takai, Tomokazu Matsuda, Yuki Matsuura, Kaho Inoue, Emi Suzuki, Ayumi Kanno, Maki Kimura-Koyanagi, Shun-Ichiro Asahara, Naoya Hatano, Wataru Ogawa, Yoshiaki Kido
During the development of type 2 diabetes, endoplasmic reticulum (ER) stress leads to pancreatic β cell failure. CCAAT/enhancer-binding protein (C/EBP) β is highly induced by ER stress and AMP-activated protein kinase (AMPK) suppression in pancreatic β cells, and its accumulation reduces pancreatic β cell mass. We investigated the phosphorylation state of C/EBPβ under these conditions. Casein kinase 2 (CK2) was found to co-localize with C/EBPβ in MIN6 cells. It phosphorylated S222 of C/EBPβ, a previously unidentified phosphorylation site...
February 12, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29448096/ampk-alleviates-endoplasmic-reticulum-stress-by-inducing-the-er-chaperone-orp150-via-foxo1-to-protect-human-bronchial-cells-from-apoptosis
#8
Ji-Qiang Liu, Li Zhang, Ji Yao, Shuo Yao, Ting Yuan
Chronic obstructive pulmonary disease (COPD), is characterized by inflammation of airways accompanied by a progressive destruction of lung parenchyma. This process is initiated in most cases by cigarette smoking. In this study we investigated the role of AMP activated protein kinase (AMPK) in cigarette smoke extract (CSE)-induced airway epithelial cell apoptosis as a consequence of endoplasmic reticulum stress (ER stress). Exposure of human bronchial epithelial cells (HBEpC) to CSE resulted in apoptosis as detected using Annexin V-PI flow cytometry...
February 12, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29447108/introducing-a-simple-model-system-for-binding-studies-of-known-and-novel-inhibitors-of-ampk-a-therapeutic-target-for-prostate-cancer
#9
Rakesh Kumar, Ranjana Maurya, Shweta Saran
Prostate cancer (PC) is one of the leading cancers in men, raising a serious health issue worldwide. Due to lack of suitable biomarker, their inhibitors and the platform for testing those inhibitors result in poor prognosis of PC. AMPK (AMP-activated protein kinase) is a highly conserved protein kinase found in eukaryotes that is involved in growth and development, and also acts as a therapeutic target for PC. The aim of the present study is to identify novel potent inhibitors of AMPK and propose a simple cellular model system for understanding its biology...
February 15, 2018: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/29446045/effects-of-extracellular-orotic-acid-on-acute-contraction-induced-adaptation-patterns-in-c2c12-cells
#10
Thomas Beiter, Jens Hudemann, Christof Burgstahler, Andreas M Nieß, Barbara Munz
Dietary administration of orotic acid (OA), an intermediate in the pyrimidine biosynthetic pathway, is considered to provide a wide range of beneficial effects, including cardioprotection and exercise adaptation. Its mechanisms of action, when applied extracellularly, however, are barely understood. In this study, we evaluated potential effects of OA on skeletal muscle using an in vitro contraction model of electrically pulse-stimulated (EPS) C2C12 myotubes. By analyzing a subset of genes representing inflammatory, metabolic, and structural adaptation pathways, we could show that OA supplementation diminishes the EPS-provoked expression of inflammatory transcripts (interleukin 6, Il6; chemokine (C-X-C Motif) ligand 5, Cxcl5), and attenuated transcript levels of nuclear receptor subfamily 4 group A member 3 (Nr4A3), early growth response 1 (Egr1), activating transcription factor 3 (Atf3), and fast-oxidative MyHC-IIA isoform (Myh2)...
February 14, 2018: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/29444592/antidepressant-like-effects-of-vaccinium-bracteatum-in-chronic-restraint-stress-mice-functional-actions-and-mechanism-explorations
#11
Dool-Ri Oh, Yujin Kim, Eun-Jin Choi, Myung-A Jung, Kyo-Nyeo Oh, Ji-Ae Hong, Donghyuck Bae, Kwangsu Kim, Huwon Kang, Jaeyong Kim, Young Ran Kim, Seung Sik Cho, Chul-Young Choi
The fruit of Vaccinium bracteatum Thunb. (VBF) is commonly known as the oriental blueberry in Korea. The aim of this study was to evaluate the antidepressant-like effects of water VBF extract (VBFW) in a mouse model of chronic restraint stress (CRS) and to identify the underlying mechanisms of its action. The behavioral effects of VBFW were assessed in the forced swim test (FST) and open field test (OFT). The levels of serum corticosterone (CORT), brain monoamines, in addition to the extracellular signal-regulated kinases (ERKs)/protein kinase B (Akt) signaling pathway were evaluated...
February 14, 2018: American Journal of Chinese Medicine
https://www.readbyqxmd.com/read/29442133/follicle-stimulating-hormone-enhances-hepatic-gluconeogenesis-by-grk2-mediated-ampk-hyperphosphorylation-at-ser485-in-mice
#12
Xiaoyi Qi, Yanjing Guo, Yongfeng Song, Chunxiao Yu, Lifang Zhao, Li Fang, Dehuan Kong, Jiajun Zhao, Ling Gao
AIMS/HYPOTHESIS: Increased serum follicle-stimulating hormone (FSH) is correlated with fasting hyperglycaemia. However, the underlying mechanism remains unclear. Because excessive hepatic gluconeogenesis is a major cause of fasting hyperglycaemia the present study investigated whether FSH increases hepatic gluconeogenesis in mice. METHODS: Ovariectomised mice supplemented with oestradiol (E2) to maintain normal levels of serum E2 (OVX+E2 mice) were injected with low or high doses of FSH...
February 13, 2018: Diabetologia
https://www.readbyqxmd.com/read/29442016/properties-and-role-of-the-quorum-sensing-molecule-farnesol-in-relation-to-the-yeast-candida-albicans
#13
S Dižová, H Bujdáková
Farnesol is a quorum sensing (QS) molecule synthesized by Candida albicans acting as a negative regulator of morphogenesis; it blocks the yeast-to-hyphae transformation. This molecule is currently studied in particular from the viewpoint of possible use as a substance with anticancer properties and with an antimicrobial, and anti-biofilm effect in yeasts resistant or tolerant to conventional therapeutic agents, for example fluconazole. Besides the aforementioned effect on morphological transformation through cyclic AMP (cAMP)/protein kinase A (cAMP-PKA) pathway, it also affects other biochemical pathways of yeasts, for example those ones for sterol biosynthesis or triggering of apoptosis via accumulation of ROS (reactive oxygen species) that damage essential cellular compartments...
June 1, 2017: Die Pharmazie
https://www.readbyqxmd.com/read/29438738/the-ampk-pgc-1%C3%AE-signaling-axis-regulates-the-astrocyte-glutathione-system-to-protect-against-oxidative-and-metabolic-injury
#14
Xiaoxin Guo, Qi Jiang, Alessandra Tuccitto, Darren Chan, Samih Alqawlaq, Gah-Jone Won, Jeremy M Sivak
Neurons are highly sensitive to metabolic and oxidative injury, but endogenous astrocyte mechanisms have a critical capacity to provide protection from these stresses. We previously reported that the master regulator PGC-1α (peroxisome proliferator-activated receptor gamma coactivator-1α) is necessary for retinal astrocytes to mount effective injury responses, with particular regard to oxidative stress. Yet, this pathway has not been well studied in glia. PGC-1α is a transcriptional co-activator that is dysregulated in a variety of neurodegenerative diseases...
February 10, 2018: Neurobiology of Disease
https://www.readbyqxmd.com/read/29438524/elevated-cyclic-amp-inhibits-mycobacterium-tuberculosis-stimulated-t-cell-ifn-%C3%AE-secretion-through-type-i-protein-kinase-a
#15
Yoon-Tae Chung, Virginia Pasquinelli, Javier O Jurado, Xisheng Wang, Na Yi, Peter F Barnes, Veronica E Garcia, Buka Samten
cAMP is critical in immune regulation, and Mycobacterium tuberculosis (Mtb) intoxicates macrophages through cAMP secretion. To examine the role of cAMP in the immune response to Mtb infection, we determined cAMP levels in peripheral blood mononuclear cells (PBMC) from tuberculosis patients and the mechanisms for cAMP suppression of T cell IFN-γ production. PBMC from tuberculosis patients contained significantly higher cAMP levels than latent tuberculosis infected subjects (LTBI), with an inverse correlation with Mtb-stimulated IFN-γ production...
February 8, 2018: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/29436644/phenformin-inhibits-cell-proliferation-and-induces-cell-apoptosis-and-autophagy-in-cholangiocarcinoma
#16
Shuyang Hu, Qing Ouyang, Qingbao Cheng, Jinghan Wang, Feiling Feng, Liang Qiao, Wei Gan, Yang Shi, Demin Wu, Xiaoqing Jiang
Cholangiocarcinoma (CCA) is an aggressive malignant tumor and the prognosis of patients with advanced stage disease remains poor. Therefore, the identification of novel treatment agents for CCA is required. In the present study, the biological effects of the diabetes therapeutic agent, phenformin, in CCA cell lines was investigated. Cell Counting Kit‑8 cell viability, cellular clone formation and subcutaneous tumor formation assays were performed, which revealed that phenformin inhibited CCA cell proliferation and growth both in vitro and in vivo...
February 8, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29435775/quercetin-prevents-in-vivo-and-in-vitro-myocardial-hypertrophy-through-the-proteasome-gsk-3-pathway
#17
Kuixiang Chen, Mubarak Rekep, Wei Wei, Qian Wu, Qin Xue, Sujuan Li, Jiahui Tian, Quan Yi, Genshui Zhang, Guiping Zhang, Qing Xiao, Jiandong Luo, Yinghua Liu
PURPOSE: Quercetin, a flavonoid, has been reported to ameliorate cardiovascular diseases, such as cardiac hypertrophy. However, the mechanism is not completely understood. In this study, a mechanism related to proteasome-glycogen synthesis kinase 3 (GSK-3) was elucidated in rats and primary neonatal cardiomyocytes. METHODS: Rats were subjected to sham or constriction of abdominal aorta surgery groups and treated with or without quercetin for 8 weeks. Angiotensin II (Ang II)-induced primary cardiomyocytes were cultured with quercetin treatment or not for 48 h...
February 12, 2018: Cardiovascular Drugs and Therapy
https://www.readbyqxmd.com/read/29435120/ampk-activation-by-tanshinone-iia-protects-neuronal-cells-from-oxygen-glucose-deprivation
#18
Yingfeng Weng, Jixian Lin, Hui Liu, Hui Wu, Zhimin Yan, Jing Zhao
The current study tested the potential neuroprotective function of Tanshinone IIA (ThIIA) in neuronal cells with oxygen-glucose deprivation (ODG) and re-oxygenation (OGDR). In SH-SY5Y neuronal cells and primary murine cortical neurons, ThIIA pre-treatment attenuated OGDR-induced viability reduction and apoptosis. Further, OGDR-induced mitochondrial depolarization, reactive oxygen species production, lipid peroxidation and DNA damages in neuronal cells were significantly attenuated by ThIIA. ThIIA activated AMP-activated protein kinase (AMPK) signaling, which was essential for neuroprotection against OGDR...
January 12, 2018: Oncotarget
https://www.readbyqxmd.com/read/29434909/fyn-knockdown-inhibits-migration-and-invasion-in-cholangiocarcinoma-through-the-activated-ampk-mtor-signaling-pathway
#19
Shao-Cheng Lyu, Dong-Dong Han, Xian-Liang Li, Jun Ma, Qiao Wu, Hong-Meng Dong, Chun Bai, Qiang He
Cholangiocarcinoma (CCA) is a rare and fatal tumor. In previous decades, there has been a steady increase in the incidence and mortality rates of this tumor worldwide. Metastasis is regarded as the major factor that contributes to poor prognosis in CCA patients. Studies therefore aim to develop novel therapeutic targets to control CCA metastasis. Fyn is known to enhance expression and promote metastasis in various cancers, including pancreatic cancer, prostate cancer and colorectal cancer. However, the exact function and mechanism of Fyn in CCA metastasis remains unclear...
February 2018: Oncology Letters
https://www.readbyqxmd.com/read/29433631/ampk-signaling-to-acetyl-coa-carboxylase-is-required-for-fasting-and-cold-induced-appetite-but-not-thermogenesis
#20
Sandra Galic, Kim Loh, Lisa Murray-Segal, Gregory R Steinberg, Zane B Andrews, Bruce E Kemp
AMP-activated protein kinase (AMPK) is a known regulator of whole-body energy homeostasis, but the downstream AMPK substrates mediating these effects are not entirely clear. AMPK inhibits fatty acid synthesis and promotes fatty acid oxidation by phosphorylation of acetyl-CoA carboxylase (ACC) 1 at Ser 79 and ACC2 at Ser 212 . Using mice with Ser 79 Ala/Ser 212 Ala knock-in mutations (ACC DKI) we find that inhibition of ACC phosphorylation leads to reduced appetite in response to fasting or cold exposure. At sub-thermoneutral temperatures, ACC DKI mice maintain normal energy expenditure and thermogenesis, but fail to increase appetite and lose weight...
February 13, 2018: ELife
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