title: Glycolytic enzyme upregulation and numbness of mitochondrial activity characterize the early phase of apoptosis in cerebellar granule cells.
abstract: Alzheimer's disease (AD) and cancer proceed via one or more common molecular mechanisms: a metabolic shift from oxidative phosphorylation to glycolysis-corresponding to the activation of the Warburg effect-occurs in both diseases. The findings reported in this paper demonstrate that, in the early phase of apoptosis, glucose metabolism is enhanced, i.e. key proteins which internalize and metabolize glucose-glucose transporter, hexokinase and phosphofructokinase-are up-regulated, in concomitance with a parallel decrease in oxygen consumption by mitochondria and increase of L-lactate accumulation. Reversal of the glycolytic phenotype occurs in the presence of dichloroacetate, inhibitor of the pyruvate dehydrogenase kinase enzyme, which speeds up apoptosis of cerebellar granule cells, reawakening mitochondria and then modulating glycolytic enzymes. Loss of the adaptive advantage afforded by aerobic glycolysis, which occurs in the late phase of apoptosis, exacerbates the pathological processes underlying neurodegeneration, leading inevitably the cell to death. In conclusion, the data propose that both aerobic, i.e. Warburg effect, essentially due to the protective numbness of mitochondria, and anaerobic glycolysis, rather due to the mitochondrial impairment, characterize the entire time frame of apoptosis, from the early to the late phase, which mimics the development of AD.
authors.affiliation: Institute of Biomembrane and Bioenergetics (IBBE) - CNR, Via Amendola 165/A, 70126, Bari, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Bobba
authors.forename: G
authors.initials: G
authors.lastname: Amadoro
authors.forename: G
authors.initials: G
authors.lastname: La Piana
authors.forename: P
authors.initials: P
authors.lastname: Calissano
authors.forename: A
authors.initials: A
authors.lastname: Atlante
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002531:Cerebellum / Q000166:cytology / Q000378:metabolism; D003999:Dichloroacetic Acid / Q000494:pharmacology; D051246:Glucose Transport Proteins, Facilitative / Q000378:metabolism; D006019:Glycolysis; D006593:Hexokinase / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism* / Q000648:ultrastructure; D010100:Oxygen / Q000378:metabolism; D025221:Phosphofructokinases / Q000378:metabolism; D061251:Primary Cell Culture; D017208:Rats, Wistar; D015854:Up-Regulation
chemical_list: D051246:Glucose Transport Proteins, Facilitative; D003999:Dichloroacetic Acid; D025221:Phosphofructokinases; D006593:Hexokinase; D010100:Oxygen