Temporal relationship of autophagy and apoptosis in neurons challenged by low molecular weight β-amyloid peptide.
Bottom Line: On the other hand, Aβ activated autophagy by inducing autophagic vesicle formation and autophagy related gene 12 (ATG12), and up-regulated the lysoso-mal machinery for the degradation of autophagosomes.Moreover, we demonstrated that activation of autophagy by Aβ preceded that of apoptosis, with death associated protein kinase phosphorylation as the potential molecular link.More importantly, under Aβ toxicity, neurons exhibiting high level of autophagosome formation were absent of apoptotic features, and inhibition of autophagy by 3-methylade-nine advanced neuronal apoptosis, suggesting that autophagy can protect neurons from Aβ-induced apoptosis.
Affiliation: Laboratory of Neurodegenerative Diseases, Department of Anatomy, The University of Hong Kong, Pokfulam, Hong Kong, China.Show MeSH
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Mentions: To examine the toxicity of low MW Aβ in causing neuronal cell death, we demonstrated that low MW Aβ induced apoptosis in neurons, but not DMSO (vehicle)-treated control. By Western blot analysis, we showed that low MW Aβ induced cleavage of caspase 3 and PARP, which are typical apoptotic features . Cleavage of these two proteins was shown to be dose- and time-dependent. It first occurred at 18 hrs of Aβ treatment and became prominent from 24 hrs onwards (Fig. 2). We also examined the effect of Aβ on AIF expression and intracellular localization. Q-PCR did not show significant induction of AIF mRNA levels upon Aβ treatment from 4 to 30 hrs (Fig. 3). Immunofluorescent analysis of AIF showed that, in vehicle-treated control, AIF signals co-localized with Mito-GFP at 8 and 24 hrs (Fig. 4). When neurons were treated with Aβ, there was no significant induction of AIF immunoreactiv-ity and the localization of AIF was comparable to the vehicle-treated control at both time-points.
Affiliation: Laboratory of Neurodegenerative Diseases, Department of Anatomy, The University of Hong Kong, Pokfulam, Hong Kong, China.