Synonym | 5-amino-1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]imidazole-4-carboxamide |
Biochem/Physiol
Actions | Acadesine is a 5-aminoimidazole-4-carboxamide (AICA) riboside, a ribnucleoside analog, and a nucleotide biosynthesis precursor with B cell pro-apoptotic activity. Following cellular uptake, acadesine is phosphorylated to AICA ribotide (ZMP), which mimics 5'-adenosine monophosphate (AMP). Both AMP-activated protein kinase (AMPK) and AMPK kinase (AMPKK) are activated by ZMP, which appears to be necessary for the induction of apoptosis. Acadesine-induced apoptosis also appears to require cytochrome c release from mitochondria and caspase activation and is p53-independent. However, the exact mechanism of acadesine-induced apoptosis is unknown. T cells are significantly less susceptible than B cells to acadesine-induced apoptosis. AMPK regulates several cellular systems including the cellular uptake of glucose, the beta-oxidation of fatty acids, protein synthesis, and
the biogenesis of glucose transporter 4 (GLUT4) and mitochondria. Acadesine, an AMPK activator, results in accumulation of ZMP, which mimics the stimulating effect of AMP on AMPK and AMPK kinase. |
