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Temporal relationship of autophagy and apoptosis in neurons challenged by low molecular weight β-amyloid peptide.

Cheung YT, Zhang NQ, Hung CH, Lai CS, Yu MS, So KF, Chang RC - J. Cell. Mol. Med. (2011)

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.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Neurodegenerative Diseases, Department of Anatomy, The University of Hong Kong, Pokfulam, Hong Kong, China.

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Low MW Aβ did not induce mito-chondrial release and nuclear entry of AIF. Neurons transfected with Mito-GFP were treated with low MW Aβ1–42 of indicated concentrations or DMSO (vehicle) for 8 or 24 hrs. The neurons were stained with anti-AIF antibody. Representative Z-stack confocal images from two independent experiments are shown. Scale bar, 10 μM.
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fig04: Low MW Aβ did not induce mito-chondrial release and nuclear entry of AIF. Neurons transfected with Mito-GFP were treated with low MW Aβ1–42 of indicated concentrations or DMSO (vehicle) for 8 or 24 hrs. The neurons were stained with anti-AIF antibody. Representative Z-stack confocal images from two independent experiments are shown. Scale bar, 10 μM.

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 [7]. 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.


Temporal relationship of autophagy and apoptosis in neurons challenged by low molecular weight β-amyloid peptide.

Cheung YT, Zhang NQ, Hung CH, Lai CS, Yu MS, So KF, Chang RC - J. Cell. Mol. Med. (2011)

Low MW Aβ did not induce mito-chondrial release and nuclear entry of AIF. Neurons transfected with Mito-GFP were treated with low MW Aβ1–42 of indicated concentrations or DMSO (vehicle) for 8 or 24 hrs. The neurons were stained with anti-AIF antibody. Representative Z-stack confocal images from two independent experiments are shown. Scale bar, 10 μM.
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Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3822792&req=5

fig04: Low MW Aβ did not induce mito-chondrial release and nuclear entry of AIF. Neurons transfected with Mito-GFP were treated with low MW Aβ1–42 of indicated concentrations or DMSO (vehicle) for 8 or 24 hrs. The neurons were stained with anti-AIF antibody. Representative Z-stack confocal images from two independent experiments are shown. Scale bar, 10 μM.
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 [7]. 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.

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.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Neurodegenerative Diseases, Department of Anatomy, The University of Hong Kong, Pokfulam, Hong Kong, China.

Show MeSH
Related in: MedlinePlus