5-amino-4-imidazolecarboxamide riboside confers strong tolerance to glucose starvation in a 5'-AMP-activated protein kinase-dependent fashion.
Acadesine, 5-amino-4-imidazolecarboxamide riboside (AICAR), has been claimed to protect the heart, lung, and small intestine against ischemic damage. The biochemical mechanisms of this effect of AICAR are not yet fully understood. To understand the mechanism, we examined the effect of AICAR on glucose starvation, since cellular responses to ischemia could be regarded as a protective response to an insufficient blood supply, cells might display adaptive reactions not only to oxygen deficiency but to nutrient deficiency. AICAR was found to confer strong tolerance to glucose starvation. By using antisense RNA expression vector for alpha subunit of 5'-AMP-activated protein kinase, the effect of AICAR was found to be dependent on 5'-AMP-activated protein kinase containing the alpha2 subunit. The AICAR effect was also dependent on the presence of amino acids, indicating an energy source switch from glucose to amino acids.
Hashimoto
Koichi
K
Investigative Treatment Division, National Cancer Center Research Institute East, 6-5-1, Kashiwanoha, Kashiwa, Chiba 277-8577, Japan.
Kato
Kazuyoshi
K
Imamura
Kazuhiro
K
Kishimoto
Atsuhiro
A
Yoshikawa
Hiroyuki
H
Taketani
Yuuji
Y
Esumi
Hiroyasu
H
D055372:AMP-Activated Protein Kinases; D000255:Adenosine Triphosphate / Q000378:metabolism; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives* / Q000378:metabolism*; D015152:Blotting, Northern; D002460:Cell Line; D002470:Cell Survival; D004268:DNA-Binding Proteins / Q000096:biosynthesis; D005347:Fibroblasts / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D000860:Hypoxia; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009097:Multienzyme Complexes / Q000378:metabolism*; D009687:Nuclear Proteins / Q000096:biosynthesis; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D010100:Oxygen / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D012313:RNA / Q000378:metabolism; D016372:RNA, Antisense / Q000378:metabolism; D012265:Ribonucleotides / Q000378:metabolism*; D013997:Time Factors; D014157:Transcription Factors; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; C497442:HIF1A protein, human; D007004:Hypoglycemic Agents; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009097:Multienzyme Complexes; D009687:Nuclear Proteins; D016376:Oligonucleotides, Antisense; D016372:RNA, Antisense; D012265:Ribonucleotides; D014157:Transcription Factors; D000620:Aminoimidazole Carboxamide; D012313:RNA; D000255:Adenosine Triphosphate; C526181:PRKAA2 protein, human; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases; C031143:AICA ribonucleotide; D005947:Glucose; D010100:Oxygen