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High School Student Local to the Baltimore Area

HS Poster

Poster 9 - AMPK Activator AICAR Modulates Cellular Responses Across Various Stress-Induced Conditions

Saturday, October 26, 2024
10:00 AM - 12:00 PM EST
Location: Exhibit Hall E, F & G

    Presenting Author(s)

  • Bahar Demirekler

    Student
    River Hill High School
    Clarksville, Maryland, United States

    • Co-Author(s)

  • JP

    Junseong Park, MS (he/him/his)

    Research Assistant
    Johns Hopkins School Of Medicine, United States

    • Primary Investigator(s)

  • Mark Ranek, PhD

    Assistant Professor
    Johns Hopkins School Of Medicine
    Baltimore, Maryland, United States


Introduction: 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR) is an adenosine monophosphate -activated protein kinase (AMPK) activator. In cells, AICAR is converted into 5-aminoimidazole-4-carboxamide ribonucleotide (ZMP), which imitates adenosine monophosphate (AMP) and activates AMPK. When AICAR activates AMPK, it causes increased fatty acid oxidation and decreased glycolysis. This study aims to observe AMPK activator AICAR in different stress-induced conditions.

Materials and

Methods: This study aims to observe the role of AICAR in different stress-induced conditions. We seeded neonatal rat ventricular myocytes (NRVMs) on 6-well plates, and treated half of them with AICAR. Then, we placed both AICAR and non-AICAR plates in five different conditions: control, carbobenzoxy-l-leucyl-l-leucyl-l-leucinal (MG132), simulated ischemia, ultraviolet (UV), and carbonyl cyanide m-chlorophenyl hydrazone (CCCP). We then ran quantitative polymerase chain reaction (qPCR) and Western Blots for all the conditions and compared them.

Results, Conclusions, and Discussions: NRVMs exposed to AICAR express higher levels of homologous to E6-AP carboxyl terminus (HECT), C-terminal ubiquitin-associated (UBA), and tryptophan-tryptophan-glutamate (WWE) domain-containing E3 ubiquitin ligase 1 (HUWE1) in ischemic conditions, while also expressing lower levels of Phosphodiesterase 9A (PDE9A) in CCCP. These observations are significant because they suggest that HUWE1 may play a role in how cells adapt to ischemic stress, potentially influenced by AICAR’s impact on stress response pathways. Targeting HUWE1 and AMPK pathways might improve the outcomes in ischemic conditions. In addition, AICAR’s activation of AMPK influences PDE9A expression, which could be positively affecting cyclic guanosine monophosphate (cGMP) signaling and the cellular stress responses. This may be helping cells adapt to disrupted mitochondria and stress, which shows AICAR potential making cells more resilient.

Acknowledgements (Optional):

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