产品号 #72702_C
AMPK activator
概述
AICAR is an adenosine analog that selectively activates AMP-activated protein kinase (AMPK). AMPK regulates lipid and glucose metabolism to maintain cellular energy homeostasis (Hardie and Carling).
MAINTENANCE & SELF-RENEWAL
· Induces upregulation of the pluripotency network genes (Klf4, Klf2, Nanog, Oct4, Myc, Sox2) and epigenetic-associated proteins (Dnmt3a, Mbd3) in mouse ES cells, and inhibits retinoic acid-induced differentiation (Adamo et al.; Shi et al).
DIFFERENTIATION
· Promotes differentiation and mineralization of MC3T3-E1 osteoblastic cells (Kanazawa et al.).
· Inhibits proliferation and promotes osteogenic differentiation, while inhibiting adipogenic differentiation, of human amnion-derived mesenchymal stem cells (MSCs) and rabbit bone marrow-derived MSCs (Wu et al.).
· Suppresses proliferation and induces astroglial differentiation in neural stem cells (NSCs) and in the immortalized NSC line C17.2 (C17.2-NSC; Zang et al. 2008, 2009).
· Decreased proliferation and Nanog expression in mouse embryonic stem (ES) cells, with increased erythroid differentiation (Chae et al.)
Alternative Names
Acadesine; AICA Riboside; NSC 105823
Cell Type
Mesenchymal Stem and Progenitor Cells, Neural Stem and Progenitor Cells, Osteoblasts, Pluripotent Stem Cells
Species
Human, Mouse, Non-Human Primate, Other, Rat
Application
Differentiation, Maintenance
Area of Interest
Neuroscience, Stem Cell Biology
CAS Number
2627-69-2
Chemical Formula
C₉H₁₄N₄O₅
Molecular Weight
258.2 g/mol
Purity
≥ 98%
Pathway
AMPK
Target
AMPK
Protocols and Documentation
Find supporting information and directions for use in the Product Information Sheet or explore additional protocols below.
Applications
This product is designed for use in the following research area(s) as part of the highlighted workflow stage(s). Explore these workflows to learn more about the other products we offer to support each research area.
Resources and Publications
Educational Materials (2)
Publications (10)
AICAR sustains J1 mouse embryonic stem cell self-renewal and pluripotency by regulating transcription factor and epigenetic modulator expression. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 2013 JAN
Abstract
BACKGROUND/AIMS [corrected] Embryonic stem cells (ES cells) have the capacity to propagate indefinitely, maintain pluripotency, and differentiate into any cell type under defined conditions. As a result, they are considered to be the best model system for research into early embryonic development. AICA ribonucleotide (AICAR) is an activator of AMP-activated protein kinase (AMPK) that is thought to affect ES cell function, but its role in ES cell fate decision is unclear. METHODS In this study, we performed microarray analysis to investigate AICAR downstream targets and further understand its effect on ES cells. RESULTS Our microarray data demonstrated that AICAR can significantly up-regulate pluripotency-associated genes and down-regulate differentiation-associated transcription factors. Although AICAR cannot maintain ES cell identity without LIF, it can antagonize the action of RA-induced differentiation. Using those differentially expressed genes identified, we performed gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis with the Database for Annotation, Visualization and Integrated Discovery (DAVID) online system. AICAR was not only shown to influence the AMPK pathway, but also act on other signaling pathways such as BMP, MAPK and TGF-β, to maintain the stemness of J1 ES cells. Furthermore, AICAR modulated ES cell epigenetic modification by altering the expression of epigenetic-associated proteins, including Dnmt3a, Dnmt3b, Smarca2, Mbd3, and Arid1a, or through regulating the transcription of long intervening non-coding RNA (lincRNA). CONCLUSION Taken together, our work suggests that AICAR is capable of maintaining ES cell self-renewal and pluripotency, which could be useful in future medical treatment.
5-Aminoimidazole-4-carboxyamide ribonucleoside induces G(1)/S arrest and Nanog downregulation via p53 and enhances erythroid differentiation. Stem cells (Dayton, Ohio) 2012 FEB
Abstract
Molecular mechanisms of how energy metabolism affects embryonic stem cell (ESC) pluripotency remain unclear. AMP-activated protein kinase (AMPK), a key regulator for controlling energy metabolism, is activated in response to ATP-exhausting stress. We investigated whether cellular energy homeostasis is associated with maintenance of self-renewal and pluripotency in mouse ESCs (mESCs) by using 5-aminoimidazole-4-carboxyamide ribonucleoside (AICAR) as an activator of AMPK. We demonstrate that AICAR treatment activates the p53/p21 pathway and markedly inhibits proliferation of R1 mESCs by inducing G(1) /S-phase cell cycle arrest, without influencing apoptosis. Treatment with AICAR also significantly reduces pluripotent stem cell markers, Nanog and stage-specific embryonic antigen-1, in the presence of leukemia inhibitory factor, without affecting expression of Oct4. H9 human ESCs also responded to AICAR with induction of p53 activation and repression of Nanog expression. AICAR reduced Nanog mRNA levels in mESCs transiently, an effect not due to expression of miR-134 which can suppress Nanog expression. AICAR induced Nanog degradation, an effect inhibited by MG132, a proteasome inhibitor. Although AICAR reduced embryoid body formation from mESCs, it increased expression levels of erythroid cell lineage markers (Ter119, GATA1, Klf1, Hbb-b, and Hbb-bh1). Although erythroid differentiation was enhanced by AICAR, endothelial lineage populations were remarkably reduced in AICAR-treated cells. Our results suggest that energy metabolism regulated by AMPK activity may control the balance of self-renewal and differentiation of ESCs.
AICAR, a small chemical molecule, primes osteogenic differentiation of adult mesenchymal stem cells. The International journal of artificial organs 2011 DEC
Abstract
The chemical approach to controlling stem cell fates is emerging as a powerful tool, holding great promise in tissue engineering and regenerative medicine. Various small molecules have been demonstrated capable of modulating stem cell differentiation. In this paper, we studied the effects of 5-aminoimidazole-4-carboxamide-1-ß-riboside (AICAR), an activator of AMP-activated protein kinase (AMPK), on mesenchymal stem cells (MSCs). AICAR at high concentrations (1.0-2.0 mM) significantly inhibited proliferation of both human amnion-derived MSCs (hAMSCs) and rabbit bone marrow-derived MSCs (BM-MSCs). Most importantly, AICAR efficiently promoted the osteogenic differentiation of hAMSCs and BM-MSCs in both growth medium and osteogenic medium. However, Metformin, another AMPK activator, showed no such effects. Meanwhile, AICAR significantly inhibited adipogenic differentiation of hAMSCs and BM-MSCs. Our data suggests that AICAR represents a potent molecule, which can be applied in bone tissue regeneration.
PRODUCTS ARE FOR RESEARCH USE ONLY AND NOT INTENDED FOR HUMAN OR ANIMAL DIAGNOSTIC OR THERAPEUTIC USES UNLESS OTHERWISE STATED. FOR ADDITIONAL INFORMATION ON QUALITY AT STEMCELL, REFER TO WWW.STEMCELL.COM/COMPLIANCE.
