Genomes and Genes
Summary: An imidazole derivative which is a metabolite of the antineoplastic agents BIC and DIC. By itself, or as the ribonucleotide, it is used as a condensation agent in the preparation of nucleosides and nucleotides. Compounded with orotic acid, it is used to treat liver diseases.
- Wang S, Zhang M, Liang B, Xu J, Xie Z, Liu C, et al. AMPKalpha2 deletion causes aberrant expression and activation of NAD(P)H oxidase and consequent endothelial dysfunction in vivo: role of 26S proteasomes. Circ Res. 2010;106:1117-28 pubmed publisher..We conclude that AMPKalpha2 functions as a physiological suppressor of NAD(P)H oxidase and ROS production in endothelial cells. In this way, AMPK maintains the nonatherogenic and noninflammatory phenotype of endothelial cells. ..
- Suzuki J, Manola A, Murakami Y, Morizane Y, Takeuchi K, Kayama M, et al. Inhibitory effect of aminoimidazole carboxamide ribonucleotide (AICAR) on endotoxin-induced uveitis in rats. Invest Ophthalmol Vis Sci. 2011;52:6565-71 pubmed publisherPURPOSE. To investigate the anti-inflammatory effect of aminoimidazole carboxamide ribonucleotide (AICAR), an analog of adenosine monophosphate (AMP), in endotoxin-induced uveitis (EIU). METHODS...
- Santidrian A, González Gironès D, Iglesias Serret D, Coll Mulet L, Cosialls A, de Frias M, et al. AICAR induces apoptosis independently of AMPK and p53 through up-regulation of the BH3-only proteins BIM and NOXA in chronic lymphocytic leukemia cells. Blood. 2010;116:3023-32 pubmed publisher..These findings support the notion that AICAR is an interesting alternative therapeutic option for CLL patients with impaired p53 function and resistance to conventional chemotherapy. ..
- Theodoropoulou S, Kolovou P, Morizane Y, Kayama M, Nicolaou F, Miller J, et al. Retinoblastoma cells are inhibited by aminoimidazole carboxamide ribonucleotide (AICAR) partially through activation of AMP-dependent kinase. FASEB J. 2010;24:2620-30 pubmed publisher..Our results indicate that AICAR-induced activation of AMPK inhibits retinoblastoma cell growth. This is one of the first descriptions of a nonchemotherapeutic drug with low toxicity that may be effective in treating Rb patients. ..
- Maarbjerg S, Jørgensen S, Rose A, Jeppesen J, Jensen T, Treebak J, et al. Genetic impairment of AMPKalpha2 signaling does not reduce muscle glucose uptake during treadmill exercise in mice. Am J Physiol Endocrinol Metab. 2009;297:E924-34 pubmed publisher..Collectively, these findings suggest that AMPKalpha2 signaling is not essential in regulating glucose uptake in mouse skeletal muscle during treadmill exercise and that other mechanisms play a central role. ..
- Guo D, Hildebrandt I, Prins R, Soto H, Mazzotta M, Dang J, et al. The AMPK agonist AICAR inhibits the growth of EGFRvIII-expressing glioblastomas by inhibiting lipogenesis. Proc Natl Acad Sci U S A. 2009;106:12932-7 pubmed publisher..These results suggest a mechanism by which AICAR inhibits the proliferation of EGFRvIII expressing glioblastomas and point toward a potential therapeutic strategy for targeting EGFR-activated cancers. ..
- Ajouz S, Decognet V, Nicot P, Bardin M. Microsatellite stability in the plant pathogen Botrytis cinerea after exposure to different selective pressures. Fungal Biol. 2010;114:949-54 pubmed publisher..This is the first study that reveals long-term stability of microsatellite markers of a spore-producing fungus exposed to different stresses. ..
- Funk R, van Haandel L, Becker M, Leeder J. Low-dose methotrexate results in the selective accumulation of aminoimidazole carboxamide ribotide in an erythroblastoid cell line. J Pharmacol Exp Ther. 2013;347:154-63 pubmed publisher..To address this issue, accumulation of the substrates for aminoimidazole carboxamide ribonucleotide transformylase (AICART) and thymidylate synthase (TS) was measured as markers of ..
- Visentin M, Zhao R, Goldman I. Augmentation of reduced folate carrier-mediated folate/antifolate transport through an antiport mechanism with 5-aminoimidazole-4-carboxamide riboside monophosphate. Mol Pharmacol. 2012;82:209-16 pubmed publisher..The transmembrane gradient for one transport substrate (ZMP) drives the uphill transport of another (folate) via a carrier used by both substrates, a phenomenon intrinsic to the energetics of RFC-mediated folate transport. ..
- Tadaishi M, Miura S, Kai Y, Kawasaki E, Koshinaka K, Kawanaka K, et al. Effect of exercise intensity and AICAR on isoform-specific expressions of murine skeletal muscle PGC-1? mRNA: a role of ??-adrenergic receptor activation. Am J Physiol Endocrinol Metab. 2011;300:E341-9 pubmed publisher..Exercise or AICAR injection increased PGC-1?-b and PGC-1?-c mRNAs via ??-AR activation, whereas high-intensity exercise increased PGC-1?-a expression by a multiple mechanism in which ?2-AMPK is one of the signaling pathways. ..
- Tong J, Yan X, Zhu M, Du M. AMP-activated protein kinase enhances the expression of muscle-specific ubiquitin ligases despite its activation of IGF-1/Akt signaling in C2C12 myotubes. J Cell Biochem. 2009;108:458-68 pubmed publisher..In addition, AMPK inhibition of mTOR may provide an additional explanation for the enhancement of UL expression by AMPK. ..
- Gaidhu M, Frontini A, Hung S, Pistor K, Cinti S, Ceddia R. Chronic AMP-kinase activation with AICAR reduces adiposity by remodeling adipocyte metabolism and increasing leptin sensitivity. J Lipid Res. 2011;52:1702-11 pubmed publisher..This led to significant reductions in VC and SC adiposity without inducing energy-sparing mechanisms that oppose long-term fat loss. ..
- Peairs A, Radjavi A, Davis S, Li L, Ahmed A, Giri S, et al. Activation of AMPK inhibits inflammation in MRL/lpr mouse mesangial cells. Clin Exp Immunol. 2009;156:542-51 pubmed publisher..Taken together, these observations suggest that AICAR inhibits LPS/IFN-gamma-induced Akt phosphorylation through AMPK activation and may serve as a potential therapeutic target in inflammatory diseases...
- Hsu M, Savas U, Lasker J, Johnson E. Genistein, resveratrol, and 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside induce cytochrome P450 4F2 expression through an AMP-activated protein kinase-dependent pathway. J Pharmacol Exp Ther. 2011;337:125-36 pubmed publisher..These results suggest that activation of AMPK by cellular stress and endocrine or pharmacologic stimulation is likely to activate CYP4F2 gene expression. ..
- Lorente Cebrián S, Bustos M, Marti A, Martinez J, Moreno Aliaga M. Eicosapentaenoic acid stimulates AMP-activated protein kinase and increases visfatin secretion in cultured murine adipocytes. Clin Sci (Lond). 2009;117:243-9 pubmed publisher..The results of the present study suggest that the stimulatory action of EPA on visfatin production involves AMPK activation in adipocytes. ..
- Wong A, Howie J, Petrie J, Lang C. AMP-activated protein kinase pathway: a potential therapeutic target in cardiometabolic disease. Clin Sci (Lond). 2009;116:607-20 pubmed publisher..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. ..
- Jeppesen J, Albers P, Rose A, Birk J, Schjerling P, Dzamko N, et al. Contraction-induced skeletal muscle FAT/CD36 trafficking and FA uptake is AMPK independent. J Lipid Res. 2011;52:699-711 pubmed publisher..However, AMPK could be important in regulation of FAT/CD36 distribution in other physiological situations. ..
- Wang X, Zhang M, Chen D, Zhang Y, Chen A. AMP-activated protein kinase rescues the angiogenic functions of endothelial progenitor cells via manganese superoxide dismutase induction in type 1 diabetes. Am J Physiol Endocrinol Metab. 2011;300:E1135-45 pubmed publisher..These findings demonstrate for the first time that AMPK activation rescues impaired EPC functions and suppresses mitochondrial superoxide by inducing MnSOD in type 1 diabetes. ..
- Robert G, Ben Sahra I, Puissant A, Colosetti P, Belhacene N, Gounon P, et al. Acadesine kills chronic myelogenous leukemia (CML) cells through PKC-dependent induction of autophagic cell death. PLoS ONE. 2009;4:e7889 pubmed publisher..Therefore, in addition to its promising effects in B-CLL, acadesine might also be beneficial for Imatinib-resistant CML patients. ..
- Kitzmann M, Lantier L, Hebrard S, Mercier J, Foretz M, Aguer C. Abnormal metabolism flexibility in response to high palmitate concentrations in myotubes derived from obese type 2 diabetic patients. Biochim Biophys Acta. 2011;1812:423-30 pubmed publisher..Interestingly, metformin treatment and mitochondrial inhibition by antimycin induced increased lipid content in control myotubes. We conclude that T2D myotubes display an impaired capacity to respond to metabolic stimuli. ..
- Theodoropoulou S, Brodowska K, Kayama M, Morizane Y, Miller J, Gragoudas E, et al. Aminoimidazole carboxamide ribonucleotide (AICAR) inhibits the growth of retinoblastoma in vivo by decreasing angiogenesis and inducing apoptosis. PLoS ONE. 2013;8:e52852 pubmed publisher..AICAR is a promising novel non-chemotherapeutic drug that may be effective as an adjuvant in treating Retinoblastoma...
- Hunter R, Treebak J, Wojtaszewski J, Sakamoto K. Molecular mechanism by which AMP-activated protein kinase activation promotes glycogen accumulation in muscle. Diabetes. 2011;60:766-74 pubmed publisher..We provide genetic evidence that AMPK activation promotes muscle glycogen accumulation by allosteric activation of GS through an increase in glucose uptake and subsequent rise in cellular [G6P]. ..
- Canto C, Gerhart Hines Z, Feige J, Lagouge M, Noriega L, Milne J, et al. AMPK regulates energy expenditure by modulating NAD+ metabolism and SIRT1 activity. Nature. 2009;458:1056-60 pubmed publisher..The AMPK-induced SIRT1-mediated deacetylation of these targets explains many of the convergent biological effects of AMPK and SIRT1 on energy metabolism. ..
- Lantier L, Mounier R, Leclerc J, Pende M, Foretz M, Viollet B. Coordinated maintenance of muscle cell size control by AMP-activated protein kinase. FASEB J. 2010;24:3555-61 pubmed publisher..Our results uncover the role of AMPK in the maintenance of muscle cell size control and highlight the crosstalk between AMPK and mTOR/p70S6K signaling pathways coordinating a metabolic checkpoint on cell growth. ..
- Anthony N, Gaidhu M, Ceddia R. Regulation of visceral and subcutaneous adipocyte lipolysis by acute AICAR-induced AMPK activation. Obesity (Silver Spring). 2009;17:1312-7 pubmed publisher..In summary, despite different fat depots eliciting distinct rates of lipolysis, acute AICAR-induced AMPK activation suppressed HSL phosphorylation/activation and exerted similar antilipolytic effects on both VC and SC adipocytes. ..
- Viscomi C, Bottani E, Civiletto G, Cerutti R, Moggio M, Fagiolari G, et al. In vivo correction of COX deficiency by activation of the AMPK/PGC-1? axis. Cell Metab. 2011;14:80-90 pubmed publisher..These results open new perspectives for therapy of mitochondrial disease. ..
- Sajan M, Bandyopadhyay G, Miura A, Standaert M, Nimal S, Longnus S, et al. AICAR and metformin, but not exercise, increase muscle glucose transport through AMPK-, ERK-, and PDK1-dependent activation of atypical PKC. Am J Physiol Endocrinol Metab. 2010;298:E179-92 pubmed publisher..On the other hand, although aPKC is activated by treadmill exercise, this activation is not required for exercise-induced increases in glucose transport, and therefore may be a redundant mechanism. ..
- Hattori Y, Suzuki K, Hattori S, Kasai K. Metformin inhibits cytokine-induced nuclear factor kappaB activation via AMP-activated protein kinase activation in vascular endothelial cells. Hypertension. 2006;47:1183-8 pubmed..Thus, it might be useful to target AMPK signaling in future efforts to prevent atherogenic and inflammatory vascular disease. ..
- Qiang W, Weiqiang K, Qing Z, Pengju Z, Yi L. Aging impairs insulin-stimulated glucose uptake in rat skeletal muscle via suppressing AMPKalpha. Exp Mol Med. 2007;39:535-43 pubmed..In conclusion, aging-related insulin resistance is associated with impaired AMPKalpha activity and could be ameliorated by AICAR, thus indicating a possible role of AMPK in aging-induced insulin resistance. ..
- Xie Z, Zhang J, Wu J, Viollet B, Zou M. Upregulation of mitochondrial uncoupling protein-2 by the AMP-activated protein kinase in endothelial cells attenuates oxidative stress in diabetes. Diabetes. 2008;57:3222-30 pubmed publisher..We conclude that AMPK activation increases UCP-2, resulting in the inhibition of both O(2).(-) and prostacyclin synthase nitration in diabetes. ..
- Robertson T, Mustard K, Lewis T, Clark J, Wyatt C, Blanco E, et al. AMP-activated protein kinase and hypoxic pulmonary vasoconstriction. Eur J Pharmacol. 2008;595:39-43 pubmed publisher..The results of the present study are consistent with the activation of AMPK being a key event in the initiation of the contractile response of pulmonary arteries to acute hypoxia. ..
- Lihn A, Pedersen S, Lund S, Richelsen B. The anti-diabetic AMPK activator AICAR reduces IL-6 and IL-8 in human adipose tissue and skeletal muscle cells. Mol Cell Endocrinol. 2008;292:36-41 pubmed publisher..In conclusion, AICAR inhibits the production of IL-6 and IL-8 human adipose tissue and in skeletal muscle cells. We suggest that decreased cytokine production might play a role for the AICAR-induced increase in insulin sensitivity. ..
- Fu X, Wan S, Lyu Y, Liu L, Qi H. Etoposide induces ATM-dependent mitochondrial biogenesis through AMPK activation. PLoS ONE. 2008;3:e2009 pubmed publisher..We propose that ATM-dependent mitochondrial biogenesis may play a role in DNA damage response and ROS regulation, and that defect in ATM-dependent mitochondrial biogenesis could contribute to the manifestations of A-T disease. ..
- Irrcher I, Ljubicic V, Kirwan A, Hood D. AMP-activated protein kinase-regulated activation of the PGC-1alpha promoter in skeletal muscle cells. PLoS ONE. 2008;3:e3614 pubmed publisher..Our data identify a novel AMPK-mediated regulatory pathway that regulates PGC-1alpha gene expression. This could represent a potential therapeutic target to control PGC-1alpha expression in skeletal muscle. ..
- Beckers A, Organe S, Timmermans L, Vanderhoydonc F, Deboel L, Derua R, et al. Methotrexate enhances the antianabolic and antiproliferative effects of 5-aminoimidazole-4-carboxamide riboside. Mol Cancer Ther. 2006;5:2211-7 pubmed
- Canabal D, Song Z, Potian J, Beuve A, McArdle J, Routh V. Glucose, insulin, and leptin signaling pathways modulate nitric oxide synthesis in glucose-inhibited neurons in the ventromedial hypothalamus. Am J Physiol Regul Integr Comp Physiol. 2007;292:R1418-28 pubmed..Finally, VMH neurons express soluble guanylyl cyclase, a downstream mediator of NO signaling. Thus NO may mediate, in part, glucose, leptin, and insulin signaling in VMH glucose-sensing neurons. ..
- Ma Z, Luo Y, Michailides T. Molecular characterization of the two-component histidine kinase gene from Monilinia fructicola. Pest Manag Sci. 2006;62:991-8 pubmed..Comparison of DNA sequences of the Mfos-1 from LIR mutants and the wild-type sensitive (S) isolate showed that LIR mutants had single point mutations in the coiled coil region of Mfos-1. ..
- Weigert C, Dufer M, Simon P, Debre E, Runge H, Brodbeck K, et al. Upregulation of IL-6 mRNA by IL-6 in skeletal muscle cells: role of IL-6 mRNA stabilization and Ca2+-dependent mechanisms. Am J Physiol Cell Physiol. 2007;293:C1139-47 pubmed..The data suggest that IL-6 could act as autocrine factor upregulating its mRNA levels, thereby supporting its function as an exercise-activated factor in skeletal muscle cells. ..
- Steinberg G, McAinch A, Chen M, O Brien P, Dixon J, Cameron Smith D, et al. The suppressor of cytokine signaling 3 inhibits leptin activation of AMP-kinase in cultured skeletal muscle of obese humans. J Clin Endocrinol Metab. 2006;91:3592-7 pubmed
- Dash P, Orsi S, Moore A. Spatial memory formation and memory-enhancing effect of glucose involves activation of the tuberous sclerosis complex-Mammalian target of rapamycin pathway. J Neurosci. 2006;26:8048-56 pubmed..Together, these findings suggest that memory formation requires the mTOR cascade and that the memory-enhancing effect of glucose involves its ability to activate this pathway. ..
- Thomson D, Herway S, Fillmore N, Kim H, Brown J, Barrow J, et al. AMP-activated protein kinase phosphorylates transcription factors of the CREB family. J Appl Physiol (1985). 2008;104:429-38 pubmed..We conclude that CREB and related proteins are direct downstream targets for AMPK and are therefore likely involved in mediating some effects of AMPK on expression of genes having a CRE in their promoters. ..
- Stuck B, Lenski M, Bohm M, Laufs U. Metabolic switch and hypertrophy of cardiomyocytes following treatment with angiotensin II are prevented by AMP-activated protein kinase. J Biol Chem. 2008;283:32562-9 pubmed publisher..Stimulation with the AMPK activator AICAR reverses these metabolic changes, increases fatty acid utilization, and inhibits cardiomyocyte hypertrophy. ..
- Jørgensen S, Treebak J, Viollet B, Schjerling P, Vaulont S, Wojtaszewski J, et al. Role of AMPKalpha2 in basal, training-, and AICAR-induced GLUT4, hexokinase II, and mitochondrial protein expression in mouse muscle. Am J Physiol Endocrinol Metab. 2007;292:E331-9 pubmed..However, the alpha2-KO did not reduce training-induced increases in HKII, GLUT4, COX-1, HAD, or CS protein in WG, suggesting that AMPKalpha2 may not be essential for metabolic adaptations of skeletal muscles to exercise training. ..
- Ouedraogo R, Wu X, Xu S, Fuchsel L, Motoshima H, Mahadev K, et al. Adiponectin suppression of high-glucose-induced reactive oxygen species in vascular endothelial cells: evidence for involvement of a cAMP signaling pathway. Diabetes. 2006;55:1840-6 pubmed..Thus, adiponectin suppresses excess ROS production under high-glucose conditions via a cAMP/PKA-dependent pathway, an effect that has implications for vascular protection in diabetes. ..
- Zhang L, Li J, Young L, Caplan M. AMP-activated protein kinase regulates the assembly of epithelial tight junctions. Proc Natl Acad Sci U S A. 2006;103:17272-7 pubmed..These results suggest that AMPK plays a role in the regulation of tight junction assembly. ..
- Towler M, Hardie D. AMP-activated protein kinase in metabolic control and insulin signaling. Circ Res. 2007;100:328-41 pubmed..It is a key player in the development of new treatments for obesity, type 2 diabetes, and the metabolic syndrome. ..
- Jensen T, Rose A, Jørgensen S, Brandt N, Schjerling P, Wojtaszewski J, et al. Possible CaMKK-dependent regulation of AMPK phosphorylation and glucose uptake at the onset of mild tetanic skeletal muscle contraction. Am J Physiol Endocrinol Metab. 2007;292:E1308-17 pubmed
- Cuthbertson D, Babraj J, Mustard K, Towler M, Green K, Wackerhage H, et al. 5-aminoimidazole-4-carboxamide 1-beta-D-ribofuranoside acutely stimulates skeletal muscle 2-deoxyglucose uptake in healthy men. Diabetes. 2007;56:2078-84 pubmed..3 +/- 0.6 to 10 +/- 0.6 mg x kg(-1) x min(-1) (P < 0.05). In healthy people, AICAR acutely stimulates muscle 2DG uptake with a minor effect on whole-body glucose disposal. ..
- Horike N, Sakoda H, Kushiyama A, Ono H, Fujishiro M, Kamata H, et al. AMP-activated protein kinase activation increases phosphorylation of glycogen synthase kinase 3beta and thereby reduces cAMP-responsive element transcriptional activity and phosphoenolpyruvate carboxykinase C gene expression in the liver. J Biol Chem. 2008;283:33902-10 pubmed publisher..Reduced CREB phosphorylation (Ser-129) associated with inactivation of GSK3beta by Ser-9 phosphorylation may be the major mechanism underlying PEPCK-C gene suppression by AMPK-activating agents such as biguanide. ..