ArticleScientific reports2016
AMPK-independent inhibition of human macrophage ER stress response by AICAR.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 28 citations in OpenAlex.
- 5-Aminoimidazole-4-carboxamide riboside, an AMPK activator, enhances TRAIL-mediated apoptosis in human bladder cancer cells in a p38 MAPK-dependent manner.Genes & genomics · 2026Article
- Endoplasmic Reticulum Stress and Its Impact on Adipogenesis: Molecular Mechanisms Implicated.Nutrients · 2023Review
- AICAR Ameliorates Non-Alcoholic Fatty Liver Disease via Modulation of the HGF/NF-κB/SNARK Signaling Pathway and Restores Mitochondrial and Endoplasmic Reticular Impairments in High-Fat Diet-Fed Rats.International journal of molecular sciences · 2023Article
- Engineering synthetic microbial consortium for cadaverine biosynthesis from glycerol.Biotechnology letters · 2022Article
- Virus-like particles displaying conserved toxin epitopes stimulate polyspecific, murine antibody responses capable of snake venom recognition.Scientific reports · 2022Article
- Roux-en-Y Gastric Bypass Modulates AMPK, Autophagy and Inflammatory Response in Leukocytes of Obese Patients.Biomedicines · 2022Article
- Contribution of endoplasmic reticulum stress, MAPK and PI3K/Akt pathways to the apoptotic death induced by a penicillin derivative in melanoma cells.Apoptosis : an international journal on programmed cell death · 2022Article
- Ginkgolide B‑induced AMPK pathway activation protects astrocytes by regulating endoplasmic reticulum stress, oxidative stress and energy metabolism induced by Aβ1‑42.Molecular medicine reports · 2021Article
- Melatonin inhibits oxalate-induced endoplasmic reticulum stress and apoptosis in HK-2 cells by activating the AMPK pathway.Cell cycle (Georgetown, Tex.) · 2020Article
- Review
- Acadesine suppresses TNF-α induced complement component 3 (C3), in retinal pigment epithelial (RPE) cells.PloS one · 2020Article
- Dysregulation of Lipid Metabolism in Macrophages Is Responsible for Severe Endotoxin Tolerance in FcgRIIB-Deficient Lupus Mice.Frontiers in immunology · 2020Article
- Metformin: A Prospective Alternative for the Treatment of Chronic Pain.Frontiers in pharmacology · 2020Review
- 5-Amino-1-β-D-Ribofuranosyl-Imidazole-4-Carboxamide (AICAR) Reduces Peripheral Inflammation by Macrophage Phenotype Shift.International journal of molecular sciences · 2019Article
- Activation of the integrated stress response in nociceptors drives methylglyoxal-induced pain.Pain · 2019Article
- Regulation of hepatic glucose production and AMPK by AICAR but not by metformin depends on drug uptake through the equilibrative nucleoside transporter 1 (ENT1).Diabetes, obesity & metabolism · 2018Article
- AXER is an ATP/ADP exchanger in the membrane of the endoplasmic reticulum.Nature communications · 2018Article
- AICAR inhibits NFκB DNA binding independently of AMPK to attenuate LPS-triggered inflammatory responses in human macrophages.Scientific reports · 2018Article
- Stearate-to-palmitate ratio modulates endoplasmic reticulum stress and cell apoptosis in non-B non-C hepatoma cells.Cancer science · 2018Article
- AICAR suppresses TNF-α-induced complement factor B in RPE cells.Scientific reports · 2017Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
Obesity-associated insulin resistance is driven by inflammatory processes in response to metabolic overload. Obesity-associated inflammation can be recapitulated in cell culture by exposing macrophages to saturated fatty acids (SFA), and endoplasmic reticulum (ER) stress responses essentially contribute to pro-inflammatory signalling. AMP-activated protein kinase (AMPK) is a central metabolic regulator with established anti-inflammatory actions. Whether pharmacological AMPK activation suppresses SFA-induced inflammation in a human system is unclear. In a setting of hypoxia-potentiated inflammation induced by SFA palmitate, we found that the AMP-mimetic AMPK activator 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR) potently suppressed upregulation of ER stress marker mRNAs and pro-inflammatory cytokines. Furthermore, AICAR inhibited macrophage ER stress responses triggered by ER-stressors thapsigargin or tunicamycin. Surprisingly, AICAR acted independent of AMPK or AICAR conversion to 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranosyl monophosphate (ZMP) while requiring intracellular uptake via the equilibrative nucleoside transporter (ENT) ENT1 or the concentrative nucleoside transporter (CNT) CNT3. AICAR did not affect the initiation of the ER stress response, but inhibited the expression of major ER stress transcriptional effectors. Furthermore, AICAR inhibited autophosphorylation of the ER stress sensor inositol-requiring enzyme 1α (IRE1α), while activating its endoribonuclease activity in vitro. Our results suggest that AMPK-independent inhibition of ER stress responses contributes to anti-inflammatory and anti-diabetic effects of AICAR.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.