AMPK-dependent and independent effects of AICAR and compound C on T-cell responses

Enyu Rao; Yuwen Zhang; Qiang Li; Jiaqing Hao; Nejat K Egilmez; Jill Suttles; Bing Li

doi:10.18632/oncotarget.9277

Back

AMPK-dependent and independent effects of AICAR and compound C on T-cell responses

Journal article

Open access

Peer reviewed

AMPK-dependent and independent effects of AICAR and compound C on T-cell responses

Enyu Rao, Yuwen Zhang, Qiang Li, Jiaqing Hao, Nejat K Egilmez, Jill Suttles and Bing Li

Oncotarget, Vol.7(23), pp.33783-33795

06/07/2016

DOI: 10.18632/oncotarget.9277

PMCID: PMC5085118

PMID: 27177226

Files and links (1)

url

https://doi.org/10.18632/oncotarget.9277View

Published (Version of record) Open Access

Abstract

As a master metabolic sensor, AMP-activated protein kinase (AMPK) is involved in different fundamental cellular processes. Regulation of AMPK activity either by agonists (e.g., AICAR) or by antagonists (e.g., Compound C) has been widely employed to study the physiological functions of AMPK. However, mounting evidence indicates AMPK-independent effects for these chemicals and how they regulate immune cell functions remains largely unknown. Herein, using T cells from AMPK conditional knockout mice and their wild type littermates, we demonstrate that AICAR and Compound C can, indeed, activate or inhibit AMPK activity in T cells, respectively. Specifically, AICAR inhibits, but Compound C promotes, Ca2+-induced T cell death in an AMPK-dependent manner. In contrast, our data also demonstrate that AICAR and Compound C inhibit T cell activation and cytokine production in an AMPK-independent manner. Moreover, we find that the AMPK-independent activity of AICAR and Compound Cis mediated via the mTOR signaling pathway in activated T cells. Our results not only reveal the critical role of AMPK in regulating T cell survival and function, but also demonstrate AMPK-dependent and independent rolesof AICAR/Compound C in regulating T cell responses, thus suggesting a context-dependent effect of these "AMPK regulators".

Phenotype

Aminoimidazole Carboxamide - analogs & derivatives

Aminoimidazole Carboxamide - pharmacology

AMP-Activated Protein Kinases - antagonists & inhibitors

AMP-Activated Protein Kinases - deficiency

AMP-Activated Protein Kinases - genetics

AMP-Activated Protein Kinases - metabolism

Animals

Calcium Signaling - drug effects

Cell Death - drug effects

Cells, Cultured

Cytokines - metabolism

Dose-Response Relationship, Drug

Enzyme Activation

Enzyme Activators - pharmacology

Genotype

Immunologic Factors - pharmacology

Lymphocyte Activation - drug effects

Mice, Knockout

Protein Kinase Inhibitors - pharmacology

Pyrazoles - pharmacology

Pyrimidines - pharmacology

Ribonucleosides - pharmacology

T-Lymphocytes - drug effects

T-Lymphocytes - enzymology

T-Lymphocytes - immunology

T-Lymphocytes - pathology

TOR Serine-Threonine Kinases - metabolism

Details

Title: Subtitle: AMPK-dependent and independent effects of AICAR and compound C on T-cell responses
Creators: Enyu Rao - University of Louisville
Yuwen Zhang - University of Louisville
Qiang Li - Shandong Provincial Hospital
Jiaqing Hao - University of Louisville
Nejat K Egilmez - University of Louisville
Jill Suttles - University of Louisville
Bing Li - University of Louisville
Resource Type: Journal article
Publication Details: Oncotarget, Vol.7(23), pp.33783-33795
DOI: 10.18632/oncotarget.9277
PMID: 27177226
PMCID: PMC5085118
NLM abbreviation: Oncotarget
ISSN: 1949-2553
eISSN: 1949-2553
Publisher: Impact Journals LLC
Grant note: R01 CA180986 / NCI NIH HHS R01 CA177679 / NCI NIH HHS R01 AI048850 / NIAID NIH HHS
Language: English
Date published: 06/07/2016
Academic Unit: Pathology; Surgery
Record Identifier: 9984696555502771

Metrics

14 Record Views

34 Times Cited - Web of Science