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AMPK is Activated During Sleep Deprivation in Caenorhabditis elegans Ryan Schuck, Edwin Li, Matthew D. Nelson Saint Joseph’s University, Department of Biology, Philadelphia, PA 19131
Author(s) -
Schuck Ryan James,
Li Edwin,
Nelson Matthew D.
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.05841
Subject(s) - ampk , caenorhabditis elegans , microbiology and biotechnology , protein kinase a , biology , amp activated protein kinase , oxidative stress , kinase , chemistry , biochemistry , gene
Sleep conserves energy and allows for its reallocation towards biosynthetic pathways, suggesting that one of sleep’s functions is cellular restoration. During times of sickness, cells are damaged and sleep is heightened, supporting an additional immune function for sleep. In some cases, sleep is directly induced by signaling mechanisms of the immune response. Work in model systems, such as Caenorhabditis elegans and Drosophila melanogaster , have identified a protective sleep state called stress‐induced sleep (SIS), which resembles sleep during sickness. SIS occurs following exposure to environmental stressors such as noxious temperatures, osmotic imbalances, physical damage and UV irradiation. While the signaling molecules regulating SIS have begun to be elucidated, the mechanisms linking sleep to cellular restoration are still unknown. A master regulator of nutrient/energy sensing, adenosine monophosphate‐activated protein kinase (AMPK), which is highly conserved from invertebrates to mammals, is a candidate for such a link. In mammalian cells, AMPK is activated by low levels of ATP and oxidative stressors, the latter occurring through the overproduction of reactive oxygen species. In both cases, activation of AMPK requires phosphorylation of a threonine residue (T172). We used CRISPR to make an AMPK mutant in C. elegans in which the predicted, homologous T172 site is changed to an alanine, to determine if this amino acid is conserved functionally. We find that these mutants live significantly shorter lives than wild type animals following exposure to paraquat, a known inducer of oxidative stress. Moreover, these animals provide us with an important control for testing our broader hypothesis that AMPK links sleep to cellular repair during SIS. To test this, we conducted a temporal western blot analysis, assessing AMPK’s phosphorylation levels during SIS in both wild type animals and those that are genetically sleep deprived. We find that AMPK is not significantly activated during times of normal SIS, however, mutant animals that lack sleep‐promoting neuropeptides, display increased AMPK activation 24 hours after stress exposure. These mutants also display reduced longevity in response to oxidative stress. We hypothesize that sleep deprivation promotes an increase in AMPK phosphorylation in an attempt to provide cellular protection/repair during SIS. Support or Funding Information NSF Award #1845020 (PI Nelson)