Toxic levels of amyloid beta peptide do not induce VEGF synthesis.
Alzheimer's disease is a neurodegenerative disorder associated with progressive loss of cognitive function and memory. Amyloid beta peptide (Abeta) is the major component of senile plaques and is known to exert its cytotoxic effect mainly by producing H2O2. Vascular endothelial growth factor (VEGF) is elevated in the cerebrospinal fluid (CSF) and brain of AD patients, and H2O2 is one of the factors that induce VEGF. Therefore, we tested whether Abeta might be responsible for the increased VEGF synthesis. We found that Abeta induced the production of H2O2 in vitro. Comparison of the amount of H2O2 required to induce VEGF synthesis in HN33 cells and the amount of H2O2 produced by 10 muM Abeta1-42 in vitro suggested that a toxic concentration of Abeta might induce VEGF synthesis in these cells. However, toxic concentrations of Abeta failed to induce VEGF synthesis in several cell systems. They also had no effect on antioxidant enzymes such as glutathione peroxidase, catalase, and peroxiredoxin in HN33 cells. Cu2+, Zn2+ and Fe3+ are known to accumulate in the brains of AD patients and promote aggregation of Abeta, and Cu2+ by itself induces synthesis of VEGF. However, there was no synergistic effect between Cu2+ and Abeta1-42 in the induction of VEGF synthesis and Zn2+ and Fe3+ also had no effect on the synthesis of VEGF, alone or in combination with Abeta.
Park
Sun-Young
SY
Department of Life Science, Pohang Univerisity of Science and Technology, Pohang 790-784, Korea.
Chae
Chi-Bom
CB
D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D002374:Catalase / Q000096:biosynthesis; D002460:Cell Line; D002712:Chlorides / Q000494:pharmacology; D003300:Copper / Q000494:pharmacology; D005290:Ferric Compounds / Q000494:pharmacology; D005979:Glutathione Peroxidase / Q000096:biosynthesis; D005998:Glycine / Q000494:pharmacology; D006801:Humans; D006822:Hybrid Cells; D006861:Hydrogen Peroxide / Q000494:pharmacology; D051379:Mice; D041681:NIH 3T3 Cells; D009942:Organometallic Compounds / Q000494:pharmacology; D010544:Peroxidases / Q000096:biosynthesis; D054464:Peroxiredoxins; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis*; D017967:Zinc Compounds / Q000494:pharmacology
D016229:Amyloid beta-Peptides; D002712:Chlorides; D005290:Ferric Compounds; D009942:Organometallic Compounds; D042461:Vascular Endothelial Growth Factor A; D017967:Zinc Compounds; C467480:vascular endothelial growth factor A, mouse; C018493:cupric glycinate; D003300:Copper; C016837:zinc chloride; D006861:Hydrogen Peroxide; D010544:Peroxidases; D054464:Peroxiredoxins; D002374:Catalase; D005979:Glutathione Peroxidase; D005998:Glycine; C024555:ferric chloride