These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Inhibition of alpha-mannosidase attenuates endoplasmic reticulum stress-induced neuronal cell death.
    Author: Miyake K, Nagai K.
    Journal: Neurotoxicology; 2009 Jan; 30(1):144-50. PubMed ID: 19028522.
    Abstract:
    N-glycosylation is crucial for proper folding of most of the proteins in the endoplasmic reticulum (ER). The N-glycans in the ER are mainly constructed of mannose. In this study, we examined whether inhibition of mannose trimming in the ER affects the susceptibility of PC-12 cells to ER stress. Pretreatment with 100 microM alpha-mannosidase inhibitor 1-deoxymannojirimycin (DMJ) in PC-12 cells significantly attenuated the cytotoxicity by ER stressors tunicamycin (TM), thapsigargin (TG), and amyloid beta1-42 (Abeta1-42), and reduced caspase-3 activation by TM and TG. Pretreatment with DMJ also protected primary cultured mouse cortical neurons from Abeta1-42 toxicity. With regard to the effect of DMJ pretreatment on ER stress signaling in PC-12 cells, DMJ attenuated TM- and TG-induced CHOP expression and TG stimulated JNK phosphorylation, which is associated with ER stress dependent cell death. Next, we examined the effect of mannose oligosaccharides, which have similar structures to N-glycans in the ER, on amyloidogenesis of Abeta1-42 that causes ER stress dependent neuronal cell death. Mannopentaose (M5) and Man9GlcNAc2 (M9) oligosaccharides significantly inhibited the amyloidogenesis of Abeta1-42. Our data suggests that inhibition of N-glycan processing in the ER attenuates ER stress-induced cell death by increasing high-mannose type oligosaccharides that reduce protein aggregation, such as amyloidogenesis.
    [Abstract] [Full Text] [Related] [New Search]