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https://www.readbyqxmd.com/read/29331024/combination-therapy-of-lovastatin-and-ampk-activator-improves-mitochondrial-and-peroxisomal-functions-and-clinical-disease-in-eae-model
#1
Inderjit Singh, Devadoss J Samuvel, Seungho Choi, Nishant Saxena, Avtar K Singh, Jeseong Won
Recent studies report that loss and dysfunction of mitochondria and peroxisomes contribute to the myelin and axonal damage in multiple sclerosis (MS). In this study, we investigated the efficacy of lovastatin and AMPK activator (AICAR) combination on the loss and dysfunction of mitochondria and peroxisomes and myelin and axonal damage in the spinal cords, relative to the clinical disease symptoms, using a mouse model of experimental autoimmune encephalomyelitis (EAE, a model for MS). We observed that lovastatin and AICAR treatments individually provided partial protection of mitochondria/peroxisomes, myelin/axons, and thus partial attenuation of clinical disease in EAE mice...
January 13, 2018: Immunology
https://www.readbyqxmd.com/read/29324976/ginsenoside-rg1-inhibits-apoptosis-by-increasing-autophagy-via-the-ampk-mtor-signaling-in-serum-deprivation-macrophages
#2
Ping Yang, Lu Ling, Wenjing Sun, Junquan Yang, Ling Zhang, Guoji Chang, Jiazhi Guo, Jun Sun, Lin Sun, Di Lu
Ginsenoside Rg1 (Rg1) has been widely used in a broad range of cardiovascular and cerebral-vascular diseases because of its unique therapeutic properties. However, the underlying mechanisms of Rg1 in the treatment of atherosclerosis have not been fully explored. This study sought to determine the precise molecular mechanisms on how Rg1 might be involved in regulating apoptosis in serum deprivation-induced Raw264.7 macrophages and primary bone marrow-derived macrophages. Results demonstrated that Rg1 treatment effectively suppressed apoptosis and the expression of phosphorylation level of mTOR induced by serum deprivation in Raw264...
January 9, 2018: Acta Biochimica et Biophysica Sinica
https://www.readbyqxmd.com/read/29321306/digitoxin-suppresses-human-cytomegalovirus-replication-via-na-k-atpase-%C3%AE-1-subunit-dependent-ampk-and-autophagy-activation
#3
Rupkatha Mukhopadhyay, Rajkumar Venkatadri, Jenny Katsnelson, Ravit Arav-Boger
Host-directed therapeutics for human cytomegalovirus (HCMV) requires elucidation of cellular mechanisms that inhibit HCMV. We report on a novel pathway used by cardiac glycosides to inhibit HCMV replication: induction of AMPK activity and autophagy flux through the Na+, K+/ATPase α1 subunit. Our data illustrate an intricate balance between autophagy regulators AMPK, mTOR and ULK1 during infection and treatment with the cardiac glycoside, digitoxin. Both infection and digitoxin induced AMPK phosphorylation, but ULK1 was differentially phosphorylated at unique sites leading to opposing effects on autophagy...
January 10, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29278707/metformin-ameliorates-activation-of-hepatic-stellate-cells-and-hepatic-fibrosis-by-succinate-and-gpr91-inhibition
#4
Giang Nguyen, So Young Park, Cong Thuc Le, Won Sun Park, Dae Hee Choi, Eun-Hee Cho
BACKGROUND: Chronic liver disease is becoming a major cause of morbidity and mortality worldwide. During liver injury, hepatic stellate cells (HSCs) trans-differentiate into activated myofibroblasts, which produce extracellular matrix. Succinate and succinate receptor (G-protein coupled receptor91, GPR91) signaling pathway has now emerged as a regulator of metabolic signaling. A previous study showed that succinate and its specific receptor, GPR91, are involved in the activation of HSCs and the overexpression of α-smooth muscle actin (α-SMA)...
December 23, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29247196/aicar-suppresses-tnf-%C3%AE-induced-complement-factor-b-in-rpe-cells
#5
Eun Jee Chung, Nikolaos E Efstathiou, Eleni K Konstantinou, Daniel E Maidana, Joan W Miller, Lucy H Young, Demetrios G Vavvas
Age related macular degeneration is the leading cause of blindness in the developed world. Although its precise cause remains elusive, dysfunction of the retinal pigment epithelium (RPE) and dysregulation of complement have been implicated in its pathogenesis. The goal of this study was to evaluate the role of an AMP-dependent kinase (AMPK) activator, 5-aminoimidazole-4-carboxamide riboside (AICAR), on tumor necrosis factor alpha (TNF-α) induction of complement factor B (CFB) in RPE cells. We found that AICAR inhibited TNF-α-induced CFB expression in ARPE-19 and human primary RPE cells in a dose-dependent fashion...
December 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29224002/the-protective-effects-of-%C3%AE-opioid-receptor-stimulation-in-hypoxic-pulmonary-hypertension-involve-inhibition-of-autophagy-through-the-ampk-mtor-pathway
#6
Yaguang Zhou, Yuanbo Wang, Xu Wang, Xin Tian, Shumiao Zhang, Fan Yang, Haitao Guo, Rong Fan, Na Feng, Min Jia, Xiaoming Gu, Yuemin Wang, Juan Li, Jianming Pei
BACKGROUND/AIMS: In a previous study, we showed that κ-opioid receptor stimulation with the selective agonist U50,488H ameliorated hypoxic pulmonary hypertension (HPH). However, the roles that pulmonary arterial smooth muscle cell (PASMC) proliferation, apoptosis, and autophagy play in κ-opioid receptor-mediated protection against HPH are still unknown. The goal of the present study was to investigate the role of autophagy in U50,488H-induced HPH protection and the underlying mechanisms...
December 8, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29222348/insulin-degrading-enzyme-contributes-to-the-pathology-in-a-mixed-model-of-type-2-diabetes-and-alzheimer-s-disease
#7
Huajie Li, Jian Wu, Linfeng Zhu, Luolin Sha, Song Yang, Jiang Wei, Lei Ji, Xiaochun Tang, Keshi Mao, Liping Cao, Ning Wei, Wei Xie, Zhilong Yang
Insulin degrading enzyme (IDE) is believed to act as a junction point of type 2 diabetes (T2D) and Alzheimer's disease (AD), however, the underlying mechanism was not completely clear yet. Transgenic APPSwe/PS1 mice were used as the AD model and were treated with streptozocin/streptozotocin (STZ) to develop a mixed mice model presenting both AD and T2D. Morris Water Maze (MWM) and recognition task were performed to trace the cognitive function. The detection of fasting plasma glucose (FPG) and plasma insulin concentration, and Oral Glucose Tolerance Test (OGTT) were used to trace the metabolism evolution...
December 8, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/29190959/effect-of-ampk-signal-pathway-on-pathogenesis-of-abdominal-aortic-aneurysms
#8
Le Yang, Lin Shen, Peixian Gao, Gang Li, Yuxiang He, Maohua Wang, Hua Zhou, Hai Yuan, Xing Jin, Xuejun Wu
Background and aims: Determine the effect of AMPK activation and inhibition on the development of AAA (abdominal aortic aneurysm). Methods: AAA was induced in ApoE-/- mice by Ang II (Angiotensin II)-infusion. AICAR (5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside) was used as AMPK activator and Compound C was used as AMPK inhibitor. We further investigate the effect of metformin, a widely used anti-diabetic drug which could activate AMPK signal pathway, on the pathogenesis of aneurysm...
November 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/29186696/a-highly-sensitive-fret-biosensor-for-ampk-exhibits-heterogeneous-ampk-responses-among-cells-and-organs
#9
Yumi Konagaya, Kenta Terai, Yusuke Hirao, Kanako Takakura, Masamichi Imajo, Yuji Kamioka, Norio Sasaoka, Akira Kakizuka, Kenta Sumiyama, Tomoichiro Asano, Michiyuki Matsuda
AMP-activated protein kinase (AMPK), a master regulator of cellular metabolism, is a potential target for type 2 diabetes. Although extensive in vitro studies have revealed the complex regulation of AMPK, much remains unknown about the regulation in vivo. We therefore developed transgenic mice expressing a highly sensitive fluorescence resonance energy transfer (FRET)-based biosensor for AMPK, called AMPKAR-EV. AMPKAR-EV allowed us to readily examine the role of LKB1, a canonical stimulator of AMPK, in drug-induced activation and inactivation of AMPK in vitro...
November 28, 2017: Cell Reports
https://www.readbyqxmd.com/read/29175208/overexpression-of-acetyl-coa-carboxylase-%C3%AE-exacerbates-podocyte-injury-in-the-kidney-of-streptozotocin-induced-diabetic-mice
#10
Yuki Tanaka, Shinji Kume, Shiro Maeda, Norihisa Osawa, Naoko Takeda, Masami Chin-Kanasaki, Keiji Isshiki, Satoshi Ugi, Itsuki Oshima, Takashi Uzu, Hiroshi Maegawa, Shin-Ichi Araki
A single nucleotide polymorphism (SNP) within the acetyl CoA carboxylase (ACC) β gene (ACACB), rs2268388, has been shown to be associated with susceptibility to development of proteinuria in patients with type 2 diabetes. To investigate the biological roles of ACCβ in the pathogenesis of diabetic nephropathy, we examined the effects of overexpression of ACACB using podocyte-specific ACACB-transgenic mice or ACACB-overexpressing murine podocytes. Podocyte-specific ACACB-transgenic mice or littermate mice were treated with streptozotocin (STZ) to induce diabetes, and 12 weeks after induction of diabetes, we examined the expression of podocyte markers to evaluate the degree of podocyte injury in these mice...
November 22, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29170419/pdgfr-signaling-mediates-hyperproliferation-and-fibrotic-responses-of-subsynovial-connective-tissue-cells-in-idiopathic-carpal-tunnel-syndrome
#11
Yuki Saito, Takako Chikenji, Yasuhiro Ozasa, Mineko Fujimiya, Toshihiko Yamashita, Anne Gingery, Kousuke Iba
Fibrosis of the subsynovial connective tissue (SSCT) is a pathognomonic change in carpal tunnel syndrome (CTS). Identification of molecular targets and anti-fibrotic therapies could provide new treatment strategies for CTS. The contribution of SSCT cells to fibrosis and the signaling pathways that initiate and aggravate fibrosis in CTS remain unknown. Here we report that platelet-derived growth factor receptor alpha (PDGFRα) positive ( + ) cells accumulate in CTS SSCT and that the presence of fibrotic growth factor, PDGF-AA, results in increased proliferation of PDGFRα+ cells via PI3K/Akt signaling pathway...
November 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29151954/cpt1c-regulated-by-ampk-promotes-papillary-thyroid-carcinomas-cells-survival-under-metabolic-stress-conditions
#12
Rui Wang, Yajun Cheng, Dongwei Su, Boshen Gong, Xiaobo He, Xinyu Zhou, Zhijun Pang, Lingtao Cheng, Yuelei Chen, Zhenzhen Yao
Background: Cancer cells have to take metabolic transformation in tumor progression when facing need of increased energy and adequate vascularization. However, molecular mechanism is not fully known. In this study, we showed that expression of carnitine palmitoyltransferase 1C (Cpt1c), as a member of the gate-keeper enzymes , which transferring long-chain fatty acids into mitochondria to further oxidation, which is regulated by AMPK promotes papillary thyroid carcinomas cells survival under metabolic stress conditions...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/29120354/trans-plasma-membrane-electron-transport-and-ascorbate-efflux-by-skeletal-muscle
#13
Amanda M Eccardt, Thomas P Bell, Lyn Mattathil, Rohan Prasad, Shannon C Kelly, Jonathan S Fisher
Trans-plasma membrane electron transport (tPMET) and the antioxidant roles of ascorbate reportedly play a role in protection of cells from damage by reactive oxygen species, which have been implicated in causing metabolic dysfunction such as insulin resistance. Skeletal muscle comprises the largest whole-body organ fraction suggesting a potential role of tPMET and ascorbate export as a major source of extracellular antioxidant. We hypothesized that skeletal muscle is capable of tPMET and ascorbate efflux. To measure these processes, we assayed the ability of cultured muscle cells, satellite cells, and isolated extensor digitorum longus (EDL) and soleus (SOL) to reduce two extracellular electron acceptors, water soluble tetrazolium salt 1 (WST-1), and dichlorophenolindophenol (DPIP)...
November 9, 2017: Antioxidants (Basel, Switzerland)
https://www.readbyqxmd.com/read/29117108/effect-of-aicar-and-5-fluorouracil-on-x-ray-repair-cross-complementing-group-1-expression-and-consequent-cytotoxicity-regulation-in-human-hct-116-colorectal-cancer-cells
#14
Ko-Chao Lee, Chien-Tsong Lin, Shun-Fu Chang, Cheng-Nan Chen, Jing-Lan Liu, Wen-Shih Huang
Colorectal cancer (CRC) is one of the leading causes of cancer mortality and 5-Fluorouracil (5-FU) is the most common chemotherapy agent of CRC. A high level of X-ray repair cross complementing group 1 (XRCC1) in cancer cells has been associated with the drug resistance occurrence. Moreover, the activation of adenosine monophosphate (AMP)-activated protein kinase (AMPK) has been indicated to regulate the cancer cell survival. Thus, this study was aimed to examine whether XRCC1 plays a role in the 5-FU/AMPK agonist (AICAR)-induced cytotoxic effect on CRC and the underlying mechanisms...
November 8, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29115402/ampk-activation-serves-a-critical-role-in-mitochondria-quality-control-via-modulating-mitophagy-in-the-heart-under-chronic-hypoxia
#15
Huagang Zhang, Bo Liu, Tianbo Li, Yun Zhu, Guiping Luo, Yunhan Jiang, Fuqin Tang, Zhao Jian, Yingbin Xiao
Mitochondrial biogenesis is one of the generally accepted regulatory mechanisms in the heart under chronic hypoxia. The precise quantity and quality control of mitochondria is critical for the survival and function of cardiomyocytes. Mitochondrial autophagy, also known as mitophagy, which selectively eliminates dysfunctional and unwanted mitochondria, is the most important type of mitochondrial quality control. However, the detailed molecular mechanisms of mitophagy in cardiomyocytes have been largely undefined...
October 26, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29089333/electrical-pulse-stimulation-induces-glut4-glucose-transporter-translocation-in-c2c12-myotubes-that-depends-on-rab8a-rab13-and-rab14
#16
Zhu Li, Yingying Yue, Fang Hu, Chang Zhang, Xiaofang Ma, Nana Li, Lihong Qiu, Maolong Fu, Liming Chen, Zhi Yao, Philip J Bilan, Amira Klip, Wenyan Niu
The signals mobilizing GLUT4 to the plasma membrane in response to muscle contraction are less known than those elicited by insulin. This disparity is undoubtedly due to lack of suitable in vitro models to study skeletal muscle contraction. We generated C2C12 myotubes stably expressing HA-tagged GLUT4 (C2C12-GLUT4HA) that contract in response to electrical pulse stimulation (EPS) and investigated molecular mechanisms regulating GLUT4HA EPS (60min, 20V, 1Hz, 24ms pulses at 976ms intervals) elicited a gain in surface GLUT4HA (GLUT4 translocation) comparably to insulin or 5-amino imidazole-4-carboxamide ribonucleotide (AICAR)...
October 31, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29063699/characterization-of-aicar-transformylase-imp-cyclohydrolase-atic-from-staphylococcus-lugdunensis
#17
Preeti Verma, Bibekananda Kar, Ritu Varshney, Partha Roy, Ashwani K Sharma
The 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) transformylase/inosine monophosphate (IMP) cyclohydrolase (ATIC) catalyzes final two steps of purine nucleotide de novo biosynthetic pathway. The present study reports the characterization of ATIC from Staphylococcus lugdunensis (SlugATIC). Apart from kinetic analysis and a detailed biophysical characterization of SlugATIC, the role of ATIC in cell proliferation has been demonstrated for the first time. The purified recombinant SlugATIC and its truncated domains exists mainly in dimeric form was revealed in gel filtration and glutaraldehyde cross linking studies...
October 24, 2017: FEBS Journal
https://www.readbyqxmd.com/read/29048631/autophagy-induction-enhances-tetrandrine-induced-apoptosis-via-the-ampk-mtor-pathway-in-human-bladder-cancer-cells
#18
Bo Kou, Wei Liu, Xu Xu, Yang Yang, Qiuyue Yi, Fengwei Guo, Jianpeng Li, Jinsong Zhou, Qingshan Kou
Tetrandrine, a bisbenzylisoquinoline alkaloid isolated from the roots of Stephania tetrandra is a traditional Chinese medicine and exerts anticancer capacity in various types of cancers. Previous studies have shown that tetrandrine induces apoptosis in bladder cancer cells via activation of the caspase cascade. However, the underlying mechanism has not yet been reported. Autophagy is a cellular process involved in the degradation of broken proteins and aging organelles to maintain homeostasis. Recent studies indicate that autophagy is implicated in cancer therapy...
September 21, 2017: Oncology Reports
https://www.readbyqxmd.com/read/29032594/implementation-of-aicar-analysis-by-gc-c-irms-for-anti-doping-purposes
#19
C Buisson, C Frelat, C Mongongu, N Martinat, M Audran
AICAR (5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside), is a naturally-occurring substance which is part to the prohibited list of WADA. It is claimed to improve physical performance when administered as a supplement. As for other endogenous compounds such as steroids, the GC-C-IRMS analysis remains an efficient tool to differentiate endogenous substances from exogenous ones. A protocol was described in the literature for the analysis of AICAR by GC-C-IRMS. The aim of the present study was to implement this protocol in our laboratory and to propose solutions to avoid the difficulties encountered...
October 15, 2017: Drug Testing and Analysis
https://www.readbyqxmd.com/read/29025860/negative-regulation-of-trpa1-by-amp-activated-protein-kinase-in-primary-sensory-neurons-as-a-potential-mechanism-of-painful-diabetic-neuropathy
#20
Shenglan Wang, Kimiko Kobayashi, Yoko Kogure, Hiroki Yamanaka, Satoshi Yamamoto, Hideshi Yagi, Koichi Noguchi, Yi Dai
AMP activated protein kinase (AMPK) is a widely expressed intracellular energy sensor that monitors and modulates energy expenditure. Transient receptor potential ankyrin 1 (TRPA1) channel is a widely recognized chemical and thermal sensor that plays vital roles in pain transduction. Here, we discovered a functional link between AMPK and TRPA1 in dorsal root ganglion (DRG) neurons, in which AMPK activation rapidly resulted in downregulation of membrane-associated TRPA1 and its channel activity within minutes...
October 12, 2017: Diabetes
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