ArticleMolecular and cellular biology2010
Characterization of Puma-dependent and Puma-independent neuronal cell death pathways following prolonged proteasomal inhibition.
Article in Molecular and cellular biology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 19 citations in OpenAlex.
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- Proteasome and Neuroprotective Effect of Hyperbaric Oxygen Preconditioning in Experimental Global Cerebral Ischemia in Rats.Frontiers in neurology · 2022Article
- Anti-Oxidative, Anti-Inflammatory and Anti-Apoptotic Effects of Flavonols: Targeting Nrf2, NF-κB and p53 Pathways in Neurodegeneration.Antioxidants (Basel, Switzerland) · 2021Review
- Neuronal cell life, death, and axonal degeneration as regulated by the BCL-2 family proteins.Cell death and differentiation · 2021Review
- β-Ecdysterone Protects SH-SY5Y Cells Against 6-Hydroxydopamine-Induced Apoptosis via Mitochondria-Dependent Mechanism: Involvement of p38(MAPK)-p53 Signaling Pathway.Neurotoxicity research · 2016Article
- Targeting glutamine metabolism in multiple myeloma enhances BIM binding to BCL-2 eliciting synthetic lethality to venetoclax.Oncogene · 2016Article
- Bok Is Not Pro-Apoptotic But Suppresses Poly ADP-Ribose Polymerase-Dependent Cell Death Pathways and Protects against Excitotoxic and Seizure-Induced Neuronal Injury.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2016Article
- Uncoupling of PUMA Expression and Apoptosis Contributes to Functional Heterogeneity in Renal Cell Carcinoma - Prognostic and Translational Implications.Translational oncology · 2015Article
- Corticospinal Motor Neurons Are Susceptible to Increased ER Stress and Display Profound Degeneration in the Absence of UCHL1 Function.Cerebral cortex (New York, N.Y. : 1991) · 2015Article
- Tumor suppression by resistant maltodextrin, Fibersol-2.Cancer biology & therapy · 2015Article
- Article
- Optogenetic reporters: Fluorescent protein-based genetically encoded indicators of signaling and metabolism in the brain.Progress in brain research · 2012Review
- Loss of nuclear factor E2-related factor 1 in the brain leads to dysregulation of proteasome gene expression and neurodegeneration.Proceedings of the National Academy of Sciences of the United States of America · 2011Article
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Proteasomal stress and the accumulation of polyubiquitinated proteins are key features of numerous neurodegenerative disorders. Previously we demonstrated that stabilization of p53 and activation of its target gene, puma (p53-upregulated mediator of apoptosis), mediated proteasome inhibitor-induced apoptosis in cancer cells. Here we demonstrated that Puma also contributed to proteasome inhibitor-induced apoptosis in mouse neocortical neurons. Although protection afforded by puma gene deletion was incomplete, we found little evidence indicating contributions from other proapoptotic BH3-only proteins. Attenuation of bax expression did not further reduce Puma-independent apoptosis, suggesting that pathways other than the mitochondrial apoptosis pathway were activated. Real-time imaging experiments in wild-type and puma-deficient neurons using a fluorescence resonance energy transfer (FRET)-based caspase sensor confirmed the involvement of a second cell death pathway characterized by caspase activation prior to mitochondrial permeabilization and, more prominently, a third, caspase-independent and Puma-independent pathway characterized by rapid cell shrinkage and nuclear condensation. This pathway involved lysosomal permeabilization in the absence of autophagy activation and was sensitive to cathepsin but not autophagy inhibition. Our data demonstrate that proteasomal stress activates distinct cell death pathways in neurons, leading to both caspase-dependent and caspase-independent apoptosis, and demonstrate independent roles for Puma and lysosomal permeabilization in this model.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.