Differential effects of "Advanced glycation endproducts" and beta-amyloid peptide on glucose utilization and ATP levels in the neuronal cell line SH-SY5Y.
Beta-amyloid peptide (Abeta) and "Advanced glycation endproducts" (AGEs) are components of the senile plaques in Alzheimer's disease patients. It has been proposed that both AGEs and Abeta exert many of their effects, which include the upregulation of pro-inflammatory cytokines, through RAGE ("receptor for advanced glycation endproducts"). To investigate whether Abeta and AGEs cause similar or identical effects on cell survival and energy metabolism, we have compared the effects of a model-AGE and Abeta on cell viability, ATP level, glucose consumption and lactate production in the neuroblastoma cell line SH-SY5Y. The results show that AGEs and Abeta increase glucose consumption and decrease ATP levels in a dose dependent manner. Furthermore, both compounds decrease mitochondrial activity measured by the MTT assay. However, only AGEs decrease the number of cells and significantly increase lactate production. These data indicate that both AGEs and Abeta can cause differential disturbances in neuronal metabolism, which may contribute to the pathophysiological findings in Alzheimer's disease. However, their signalling pathways are apparently quite distinct, a fact which should stimulate a more detailed investigation in this field, e.g. for the purpose of a rational design of potential "neuroprotective" RAGE antagonists.
Kuhla
B
B
Neuroimmunological Cell Biology Unit, IZKF Leipzig, Leipzig, Germany.
Loske
C
C
Garcia De Arriba
S
S
Schinzel
R
R
Huber
J
J
Münch
G
G
D000255:Adenosine Triphosphate / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000494:pharmacology / Q000502:physiology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D005947:Glucose / Q000378:metabolism*; D017127:Glycation End Products, Advanced / Q000494:pharmacology / Q000502:physiology*; D006801:Humans; D019344:Lactic Acid / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D010446:Peptide Fragments / Q000494:pharmacology; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000378:metabolism
D016229:Amyloid beta-Peptides; D017127:Glycation End Products, Advanced; D010446:Peptide Fragments; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; C078592:amyloid beta-protein (1-40); D019344:Lactic Acid; D000255:Adenosine Triphosphate; D005947:Glucose