Amelioration of LPS-Induced Inflammation Response in Microglia by AMPK Activation

Chen, Chin Chen; Lin, Jiun Tsai; Cheng, Yi; Kuo, Cheng Yi; Huang, Chun Fang; Kao, Shao‐Hsuan; Liang, Yao Jen; Cheng, Ching Yi; Chen, Han Min

doi:10.1155/2014/692061

Cited by 33 publications

(37 citation statements)

References 37 publications

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“…In fact, it has been demonstrated that in human vascular endothelial cells, the anti-inflammatory effect of adenine is mediated by its APRT-catalysed conversion into AMP and the subsequent activation of AMPK [96]. The same observation has been reported for murine microglial cells [97]. Adenine has also been demonstrated to cause cell cycle arrest and trigger autophagy in myelogenous leukaemia cells through the activation of AMPK.…”

Section: Adenine Phosphoribosyltransferasementioning

confidence: 59%

Interplay between adenylate metabolizing enzymes and AMP‐activated protein kinase

Camici¹,

Allegrini²,

Tozzi³

2018

The FEBS Journal

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Purine nucleotides are involved in a variety of cellular functions, such as energy storage and transfer, and signalling, in addition to being the precursors of nucleic acids and cofactors of many biochemical reactions. They can be generated through two separate pathways, the de novo biosynthesis pathway and the salvage pathway. De novo purine biosynthesis leads to the formation of IMP, from which the adenylate and guanylate pools are generated by two additional steps. The salvage pathways utilize hypoxanthine, guanine and adenine to generate the corresponding mononucleotides. Despite several decades of research on the subject, new and surprising findings on purine metabolism are constantly being reported, and some aspects still need to be elucidated. Recently, purine biosynthesis has been linked to the metabolic pathways regulated by AMP-activated protein kinase (AMPK). AMPK is the master regulator of cellular energy homeostasis, and its activity depends on the AMP : ATP ratio. The cellular energy status and AMPK activation are connected by AMP, an allosteric activator of AMPK. Hence, an indirect strategy to affect AMPK activity would be to target the pathways that generate AMP in the cell. Herein, we report an up-to-date review of the interplay between AMPK and adenylate metabolizing enzymes. Some aspects of inborn errors of purine metabolism are also discussed.

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Section: Adenine Phosphoribosyltransferasementioning

confidence: 59%

Interplay between adenylate metabolizing enzymes and AMP‐activated protein kinase

Camici¹,

Allegrini²,

Tozzi³

2018

The FEBS Journal

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“…The majority of the published data on the bioenergetics of polarization states has been generated in peripheral immune cells (Biswas and Mantovani, ; O'Neill and Hardie, ; Pearce and Pearce, ) with only a few studies examining microglia (Moss and Bates, ; Chenais et al ., ; Bernhart et al ., ; Sohn et al ., ; Voloboueva et al ., ; Gimeno‐Bayon et al ., ). The majority of microglia studies were related to the generation of ROS (Innamorato et al ., ; Ferger et al ., ; Bordt and Polster, ; Chen et al ., ). As in macrophages, microglia in the surveillance state are likely to rely on oxidative phosphorylation metabolism (Cherry et al ., ).…”

Section: Introductionmentioning

confidence: 99%

Microglial M1/M2 polarization and metabolic states

Orihuela

McPherson

Harry

2015

British J Pharmacology

1,543

1,279

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Microglia are critical nervous system-specific immune cells serving as tissue-resident macrophages influencing brain development, maintenance of the neural environment, response to injury and repair. As influenced by their environment, microglia assume a diversity of phenotypes and retain the capability to shift functions to maintain tissue homeostasis. In comparison with peripheral macrophages, microglia demonstrate similar and unique features with regards to phenotype polarization, allowing for innate immunological functions. Microglia can be stimulated by LPS or IFN-γ to an M1 phenotype for expression of pro-inflammatory cytokines or by IL-4/IL-13 to an M2 phenotype for resolution of inflammation and tissue repair. Increasing evidence suggests a role of metabolic reprogramming in the regulation of the innate inflammatory response. Studies using peripheral immune cells demonstrate that polarization to an M1 phenotype is often accompanied by a shift in cells from oxidative phosphorylation to aerobic glycolysis for energy production. More recently, the link between polarization and mitochondrial energy metabolism has been considered in microglia. Under these conditions, energy demands would be associated with functional activities and cell survival and thus, may serve to influence the contribution of microglia activation to various neurodegenerative conditions. This review examines the polarization states of microglia and their relationship to mitochondrial metabolism. Additional supporting experimental data are provided to demonstrate mitochondrial metabolic shifts in primary microglia and the BV-2 microglia cell line induced under LPS (M1) and IL-4/IL-13 (M2) polarization. Abbreviations2-DG, 2-deoxy-glucose; AMPK, AMP-activated PK; BBB, blood-brain barrier; CD172 (SIRP1A), signal-regulatory protein; CD206, mannose receptor; EAE, experimental autoimmune encephalomyelitis; FA, fatty acid; Fizz1, found in inflammatory zone 1; HK, hexokinase; iNOS, inducible NOS; MHC-II, major histocompatibility complex-II; NLRP, nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing; NODs, nucleotide-binding oligomerization domains; PPP, pentose phosphate pathway; RNS, reactive nitrogen species; ROS, reactive oxygen species; SR, scavenger receptor; TCA, tricarboxylic acid cycle; TLR, Toll-like receptor. DOI:10.1111/bph.13139 www.brjpharmacol.org Published 2015. This article is a U.S. Government work and is in the public domain in the USA Themed Section: Inflammation: maladies, models, mechanisms and molecules LINKED ARTICLESThis article is part of a themed section on Inflammation: maladies, models, mechanisms and molecules. IntroductionThe innate immune response of the body recruits a number of different cells to initiate a response to a novel stimulus such as a pathogen. These various cells of the immune system communicate and cooperate in a complex fashion to successfully complete their assigned tasks to clear the invading factor and return the system back to homeostasis. Such cells include ...

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“…They associate closely with the vasculature and play a key role in retinal vascular development [6,7], remodeling [8] and repair [9]. Activated microglia can cause tissue damage by the production of an array of cytotoxic factors including superoxide, nitric oxide [10,11], TNF-α [12,13], andIL1-β [14]. Microglia become activated in response to diverse stimuli, including neuronal damage, disease proteins and environmental toxins.…”

Section: Introductionmentioning

confidence: 99%

Treatment with polyamine oxidase inhibitor reduces microglial activation and limits vascular injury in ischemic retinopathy

Patel

Shosha

et al. 2016

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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Retinal vascular injury is a major cause of vision impairment in ischemic retinopathies. Insults such as hyperoxia, oxidative stress and inflammation contribute to this pathology. Previously, we showed that hyperoxia-induced retinal neurodegeneration is associated with increased polyamine oxidation. Here, we are studying the involvement of polyamine oxidases in hyperoxia-induced injury and death of retinal vascular endothelial cells. Newborn C57BL6/J mice were exposed to hyperoxia (70% O2) from postnatal day (P) 7 to 12 and were treated with the polyamine oxidase inhibitor MDL 72527 or vehicle starting at P6. Mice were sacrificed after different durations of hyperoxia and their retinas were analyzed to determine the effects on vascular injury, microglial cell activation, and inflammatory cytokine profiling. The results of this analysis showed that MDL 72527 treatment significantly reduced hyperoxia-induced retinal vascular injury and enhanced vascular sprouting as compared with the vehicle controls. These protective effects were correlated with significant decreases in microglial activation as well as levels of inflammatory cytokines and chemokines. In order to model the effects of polyamine oxidation in causing microglial activation in vitro, studies were performed using rat brain microvascular endothelial cells treated with conditioned-medium from rat retinal microglia stimulated with hydrogen peroxide. Conditioned-medium from activated microglial cultures induced cell stress signals and cell death in microvascular endothelial cells. These studies demonstrate the involvement of polyamine oxidases in hyperoxia-induced retinal vascular injury and retinal inflammation in ischemic retinopathy, through mechanisms involving cross-talk between endothelial cells and resident retinal microglia.

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Amelioration of LPS-Induced Inflammation Response in Microglia by AMPK Activation

Cited by 33 publications

References 37 publications

Interplay between adenylate metabolizing enzymes and AMP‐activated protein kinase

Interplay between adenylate metabolizing enzymes and AMP‐activated protein kinase

Microglial M1/M2 polarization and metabolic states

Treatment with polyamine oxidase inhibitor reduces microglial activation and limits vascular injury in ischemic retinopathy

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