AMPK in Pathogens

Mesquita, Inês; Moreira, Diana; Sampaio‐Marques, Belém; Laforge, Mireille; Cordeiro-da-Silva, Anabela; Ludovico, Paula; Estaquier, Jérǒme; Silvestre, Ricardo

doi:10.1007/978-3-319-43589-3_12

Cited by 9 publications

(9 citation statements)

References 183 publications

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“…AMPK functions as a modulator of host defenses against intracellular bacterial, viral, and parasitic infections [ 9 , 10 , 11 , 12 ]. Indeed, numerous viruses have the ability to trigger metabolic changes, thereby modulating AMPK activity and substrate selection [ 13 ], and AMPK signaling could facilitate or inhibit intracellular viral replication depending on the virus infection [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

AMP-Activated Protein Kinase and Host Defense against Infection

Silwal

Kim

Yuk

et al. 2018

IJMS

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5′-AMP-activated protein kinase (AMPK) plays diverse roles in various physiological and pathological conditions. AMPK is involved in energy metabolism, which is perturbed by infectious stimuli. Indeed, various pathogens modulate AMPK activity, which affects host defenses against infection. In some viral infections, including hepatitis B and C viral infections, AMPK activation is beneficial, but in others such as dengue virus, Ebola virus, and human cytomegaloviral infections, AMPK plays a detrimental role. AMPK-targeting agents or small molecules enhance the antiviral response and contribute to the control of microbial and parasitic infections. In addition, this review focuses on the double-edged role of AMPK in innate and adaptive immune responses to infection. Understanding how AMPK regulates host defenses will enable development of more effective host-directed therapeutic strategies against infectious diseases.

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Section: Introductionmentioning

confidence: 99%

AMP-Activated Protein Kinase and Host Defense against Infection

Silwal

Kim

Yuk

et al. 2018

IJMS

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“…Adenosine 5′-monophosphate-activated protein kinase has been extensively studied as a pivotal regulator of cellular energy metabolism ( 47 ). Recent studies have revealed that AMPK was involved in the regulation of virus replication ( 18 ). Inhibition of AMPK severely attenuated HCMV replication, suggesting that AMPK was required for HCMV replication ( 48 , 49 ).…”

Section: Discussionmentioning

confidence: 99%

“…Adenosine 5′-monophosphate-activated protein kinase (AMPK) is a heterotrimeric serine/threonine kinase ( 17 ), which is considered as pivotal regulator of host cellular metabolism via sensing cellular energy status ( 18 ). When the energy levels in cells decrease, AMPK is activated through phosphorylation by an upstream kinase ( 18 ). Activated AMPK thereby downregulates anabolic processes that consume ATP and upregulates catabolic processes that synthesize ATP ( 18 ).…”

Section: Introductionmentioning

confidence: 99%

“…When the energy levels in cells decrease, AMPK is activated through phosphorylation by an upstream kinase ( 18 ). Activated AMPK thereby downregulates anabolic processes that consume ATP and upregulates catabolic processes that synthesize ATP ( 18 ). Given the role of sensing changes of cellular energy status, it is not surprising that AMPK plays an important role in virus infection ( 19 ).…”

Section: Introductionmentioning

confidence: 99%

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MicroRNA miR-214 Inhibits Snakehead Vesiculovirus Replication by Promoting IFN-α Expression via Targeting Host Adenosine 5′-Monophosphate-Activated Protein Kinase

et al. 2017

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BackgroundSnakehead vesiculovirus (SHVV), a new rhabdovirus isolated from diseased hybrid snakehead, has emerged as an important pathogen during the past few years in China with great economical losses in snakehead fish cultures. However, little is known about the mechanism of its pathogenicity. MicroRNAs are small noncoding RNAs that posttranscriptionally modulate gene expression and have been indicated to regulate almost all cellular processes. Our previous study has revealed that miR-214 was downregulated upon SHVV infection.ResultsThe overexpression of miR-214 in striped snakehead (SSN-1) cells inhibited SHVV replication and promoted IFN-α expression, while miR-214 inhibitor facilitated SHVV replication and reduced IFN-α expression. These findings suggested that miR-214 negatively regulated SHVV replication probably through positively regulating IFN-α expression. Further investigation revealed that adenosine 5′-monophosphate-activated protein kinase (AMPK) was a target gene of miR-214. Knockdown of AMPK by siRNA inhibited SHVV replication and promoted IFN-α expression, suggesting that cellular AMPK positively regulated SHVV replication and negatively regulated IFN-α expression. Moreover, we found that siAMPK-mediated inhibition of SHVV replication could be partially restored by miR-214 inhibitor, indicating that miR-214 inhibited SHVV replication at least partially via targeting AMPK.ConclusionThe findings of this study complemented our early study, and provide insights for the mechanism of SHVV pathogenicity. SHVV infection downregulated miR-214, and in turn, the downregulated miR-214 increased the expression of its target gene AMPK, which promoted SHVV replication via reducing IFN-α expression. It can therefore assume that cellular circumstance with low level of miR-214 is beneficial for SHVV replication and that SHVV evades host antiviral innate immunity through decreasing IFN-α expression via regulating cellular miR-214 expression.

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“…It is most likely that T. cruzi profits from the stress generated from ROS, and this might provide an adaptive evolutionary advantage for the parasite. Many evidences point towards that direction: parasites can proliferate in response to H 2 O 2 [ 47 ] and the increased growth of epimastigotes in response to H 2 O 2 involves a calmodulin-dependent protein kinase II CAMKII-like enzyme in the proliferation pathway and a cascade of events including AMP kinase in the host [ 38 , 56 , 57 ] and also the mitochondrial ROS produced into the mitochondria, which results from heme metabolism and enhances the parasite growth [ 49 ]. As mentioned earlier, heme also controls the activity of TcK2 and in turn the process of translation in the parasite.…”

Section: Introductionmentioning

confidence: 99%

Dual and Opposite Roles of Reactive Oxygen Species (ROS) in Chagas Disease: Beneficial on the Pathogen and Harmful on the Host

Maldonado

Rojas

Morales

et al. 2020

Oxidative Medicine and Cellular Longevity

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Chagas disease is a neglected tropical disease, which affects an estimate of 6-7 million people worldwide. Chagas disease is caused by Trypanosoma cruzi, which is a eukaryotic flagellate unicellular organism. At the primary infection sites, these parasites are phagocytized by macrophages, which produce reactive oxygen species (ROS) in response to the infection with T. cruzi. The ROS produce damage to the host tissues; however, macrophage-produced ROS is also used as a signal for T. cruzi proliferation. At the later stages of infection, mitochondrial ROS is produced by the infected cardiomyocytes that contribute to the oxidative damage, which persists at the chronic stage of the disease. The oxidative damage leads to a functional impairment of the heart. In this review article, we will discuss the mechanisms by which T. cruzi is able to deal with the oxidative stress and how this helps the parasite growth at the acute phase of infection and how the oxidative stress affects the cardiomyopathy at the chronic stage of the Chagas disease. We will describe the mechanisms used by the parasite to deal with ROS and reactive nitrogen species (RNS) through the trypanothione and the mechanisms used to repair the damaged DNA. Also, a description of the events produced by ROS at the acute and chronic stages of the disease is presented. Lastly, we discuss the benefits of ROS for T. cruzi growth and proliferation and the possible mechanisms involved in this phenomenon. Hypothesis is put forward to explain the molecular mechanisms by which ROS triggers parasite growth and proliferation and how ROS is able to produce a long persisting damage on cardiomyocytes even in the absence of the parasite.

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AMPK in Pathogens

Cited by 9 publications

References 183 publications

AMP-Activated Protein Kinase and Host Defense against Infection

AMP-Activated Protein Kinase and Host Defense against Infection

MicroRNA miR-214 Inhibits Snakehead Vesiculovirus Replication by Promoting IFN-α Expression via Targeting Host Adenosine 5′-Monophosphate-Activated Protein Kinase

Dual and Opposite Roles of Reactive Oxygen Species (ROS) in Chagas Disease: Beneficial on the Pathogen and Harmful on the Host

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