Prior Treatment with AICAR Causes the Selective Phosphorylation of mTOR Substrates in C2C12 Cells

Author:

Dedert Cass J.1ORCID,Bagdady Kazimir R.1,Fisher Jonathan S.1ORCID

Affiliation:

1. Department of Biology, Saint Louis University, St. Louis, MO 63103, USA

Abstract

Metabolic stress in skeletal muscle cells causes sustained metabolic changes, but the mechanisms of the prolonged effects are not fully known. In this study, we tested C2C12 cells with the AMP-activated protein kinase (AMPK) stimulator AICAR and measured the changes in the metabolic pathways and signaling kinases. AICAR caused an acute increase in the phosphorylation of the AMPK target ULK1, the mTORC1 substrate S6K, and the mTORC2 target Akt. Intriguingly, prior exposure to AICAR only decreased glucose-6 phosphate dehydrogenase activity when it underwent three-hour recovery after exposure to AICAR in a bicarbonate buffer containing glucose (KHB) instead of Dulbecco’s Minimum Essential Medium (DMEM). The phosphorylation of the mTORC1 target S6K was increased after recovery in DMEM but not KHB, although this appeared to be specific to S6K, as the phosphorylation of the mTORC1 target site on ULK1 was not altered when the cells recovered in DMEM. The phosphorylation of mTORC2 target sites was also heterogenous under these conditions, with Akt increasing at serine 473 while other targets (SGK1 and PKCα) were unaffected. The exposure of cells to rapamycin (an mTORC1 inhibitor) and PP242 (an inhibitor of both mTOR complexes) revealed the differential phosphorylation of mTORC2 substrates. Taken together, the data suggest that prior exposure to AICAR causes the selective phosphorylation of mTOR substrates, even after prolonged recovery in a nutrient-replete medium.

Funder

National Institute of Diabetes and Digestive and Kidney Diseases

Publisher

MDPI AG

Subject

Microbiology (medical),Molecular Biology,General Medicine,Microbiology

Reference52 articles.

1. 5-aminoimidazole-4-carboxamide ribonucleoside. A specific method for activating AMP-activated protein kinase in intact cells?;Corton;Eur. J. Biochem.,1995

2. AMPK: Sensing Glucose as well as Cellular Energy Status;Lin;Cell Metab.,2018

3. AICA riboside increases AMP-activated protein kinase, fatty acid oxidation, and glucose uptake in rat muscle;Merrill;Am. J. Physiol. Metab.,1997

4. Evidence for 5’ AMP-activated protein kinase mediation of the effect of muscle contraction on glucose transport;Hayashi;Diabetes,1998

5. AMP-activated protein kinase suppresses protein synthesis in rat skeletal muscle through down-regulated mammalian target of rapamycin (mTOR) signaling;Bolster;J. Biol. Chem.,2002

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