|
KMID : 0667720000370000396
|
|
Report Natlonal Institute of Health
2000 Volume.37 No. 0 p.396 ~ p.397
|
|
|
Role of neurotrophic factors in amyloid petide induced neurotoxicity
|
|
이미경/Lee, M. K.
강병학/박진실/안상미/Kang, B. H./Park, J. S./Ahn, S. M.
|
|
|
Abstract
|
|
|
Purpose: Alzheimer´s disease(AD) is a neurodegenerative disorder characterized by progressive cognitive ecline resulting from the loss of neurons. Senile plaques, deposit of beta-amyloid peptide (Aβ) are known as e hallmark of neuropathological feature of AD, but the role of Aβ in AD pathogenesis is not well understood. In this study, we investigated the mechanism of Aβ in neuronal cell death and the effect of eurotrophic factors on Aβ -mediated neurotoxicity.
Methods: The effect of Aβ on NO production in SHSY5Y, human neuronal cell lines. was determined. The amounts of NO produced were measured by an NO analyzer or by the Griess method and the expression nNOS and iNOS was determined by RT-PCR and Western blot. analyses Neurotoxicity was assessed by MTT assay.
Result. Treatment the neuronal cells with Aβ showed no the effect on nNOS protein and mRNA level as well as the No productlin, and the incubation with NOS inhibitor did not protect neuronal cells from Aβ toxicity. These results suggested that treatment of Aβ did not induce NO production and nNOS expression to ric level in neuronal cell lines. However, increased mRNA expression of protein inhibitor of nNOS (PIN) by Aβ treatment showed the possibility that Aβ might affect other regulatory factors related to nNOS NO ner, SIN showed dual effects on Aβ-induced toxicity: SIN showed the neuroprotective activity at the lower centrations than 5OμM but the toxic effect at the higher concentrations than 100μM. These results suggested that NO modalates the Aβ-induced nearonal cell respongs We also evaluated the effects showed protective effects. of neurotrophic factors. on Aβ-induced nearotoxicty. Of ten neurotrophic factors tested, DNF, NT-3 and bFGF. In addition, bFGF induced NO production in astrocyte via MAP kinase pathway. NO oduction bY bFGF was reduced by an cAMP analog and forskolin and potentiated bya. PI3 kinase inhibifor.
Conclusion: Our study suggested that the neurotoxicity of Aβ is not derived from NO produced by urons but mediated by NO produced in astrocyte. Neurotrophic factor such as bFGF showed neuroprotective effect but also activated astroglial cells to generate NO which night, intarn, be harmfal to neurons. Therefore, is necessary to reconsider the role of neurotrophic factor in neurological disease.
|
|
|
KEYWORD
|
|
|
|
|
|
FullTexts / Linksout information
|
|
|
|
|
|
Listed journal information
|
|
|
|
|