High-glucose toxicity is mediated by AICAR-transformylase/IMP cyclohydrolase and mitigated by AMP-activated protein kinase in Caenorhabditis elegans.

ABSTRACT: The enzyme AICAR-transformylase/IMP cyclohydrolase (ATIC) catalyzes the last two steps of purine de novo synthesis. It metabolizes 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR), which is an AMP analogue, leading to activation of AMP-activated kinase (AMPK). We investigated whether the AICAR-ATIC pathway plays a role in the high glucose (HG)-mediated DNA damage response and AICAR-mediated AMPK activation, explaining the detrimental effects of glucose on neuronal damage and shortening of the lifespan. HG up-regulated the expression and activity of the Caenorhabditis elegans homologue of ATIC, C55F2.1 (atic-1), and increased the levels of reactive oxygen species and methylglyoxal-derived advanced glycation end products. Overexpression of atic-1 decreased th

SUBMITTER: Riedinger C 

PROVIDER: S-EPMC5880143 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature