Beta-amyloid peptides induces neuronal apoptosis via a mechanism independent of unfolded protein responses.
Accumulation of beta-amyloid (Abeta) peptides in senile plaques is one of the pathological hallmarks in Alzheimer's disease (AD), which can trigger apoptosis. We have previously demonstrated that Abeta triggered calcium release from the ER. Depletion of ER Ca(2+) ions has been reported leading to unfolded protein responses (UPR). While hypothesis has been made about UPR and neurodegeneration in AD, little is known about the effects of extracellular accumulation of Abeta on UPR. We have shown previously that activation of PKR in Abeta-triggered apoptosis. Since UPR can trigger PKR, our study aims to elucidate whether extracellular accumulation of Abeta peptides induce UPR in cultured neurons. Our results showed that Abeta could not trigger UPR signalings including phosphorylation of PERK, alternative cleavage of xbp-1 mRNA and induction of transcription of xbp-1 and Gadd153. Taken together, our results suggest that extracellular accumulation of Abeta peptides induce apoptosis via a mechanism independent of UPR.
Yu
Man-Shan
MS
Laboratory of Neurodegenerative Diseases, Department of Anatomy, Research Centre of Heart, Brain, Hormone and Healthy Aging, Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR.
Suen
Ka-Chun
KC
Kwok
Nga-Sze
NS
So
Kwok-Fai
KF
Hugon
Jacques
J
Chang
Raymond Chuen-Chung
RC
D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D050976:Basic-Leucine Zipper Transcription Factors / Q000378:metabolism; D018929:Cell Culture Techniques; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000196:embryology; D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D010446:Peptide Fragments / Q000494:pharmacology; D011489:Protein Denaturation / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D000071701:Regulatory Factor X Transcription Factors; D013997:Time Factors; D014157:Transcription Factors; D000071717:X-Box Binding Protein 1
D016229:Amyloid beta-Peptides; D050976:Basic-Leucine Zipper Transcription Factors; D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; D010446:Peptide Fragments; D012333:RNA, Messenger; D000071701:Regulatory Factor X Transcription Factors; D014157:Transcription Factors; D000071717:X-Box Binding Protein 1; C000605545:Xbp1 protein, rat; C075222:amyloid beta-protein (1-42); C407125:amyloid beta-protein (10-35)