The DOI matches its Crossref record; 10 of the 10 references it cites were found in a registry or an index.
Involvement of autophagy in hypoxic-excitotoxic neuronal death
Open accessAbstract
Neuronal autophagy is increased in numerous excitotoxic conditions including neonatal cerebral hypoxia-ischemia (HI). However, the role of this HI-induced autophagy remains unclear. To clarify this role we established an in vitro model of excitotoxicity combining kainate treatment (Ka, 30 µM) with hypoxia (Hx, 6% oxygen) in primary neuron cultures. KaHx rapidly induced excitotoxic death that was completely prevented by MK801 or EGTA. KaHx also stimulated neuronal autophagic flux as shown by a rise in autophagosome number (increased levels of LC3-II and punctate LC3 labeling) accompanied by increases in lysosomal abundance and activity (increased SQSTM1/p62 degradation, and increased LC3-II levels in the presence of lysosomal inhibitors) and fusion (shown using an RFP-GFP-LC3 reporter). To determine the role of the enhanced autophagy we applied either pharmacological autophagy inhibitors (3-methyladenine or pepstatinA/E64) or lentiviral vectors delivering shRNAs targeting Becn1 or Atg7. Both strategies reduced KaHx-induced neuronal death. A prodeath role of autophagy was also confirmed by the enhanced toxicity of KaHx in cultures overexpressing BECN1 or ATG7. Finally, in vivo inhibition of autophagy by intrastriatal injection of a lentiviral vector expressing a Becn1-targeting shRNA increased the volume of intact striatum in a rat model of severe neonatal cerebral HI. These results clearly show a death-mediating role of autophagy in hypoxic-excitotoxic conditions and suggest that inhibition of autophagy should be considered as a neuroprotective strategy in HI brain injuries.
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Guidelines for the use and interpretation of assays for monitoring autophagy
Klionsky, D. J., Abdalla, F. C., Abeliovich, H., Abraham, R. T., Acevedo-Arozena, A., Adeli, K., Agholme, L., Agnello, M., Agostinis, P., Aguirre-Ghiso, J. A., et al. (2012) · Autophagy · doi:10.4161/auto.19496 · Cited by 3,996 · cited 1×
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BackgroundSelf-citationSuppression of basal autophagy in neural cells causes neurodegenerative disease in mice
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Loss of autophagy in the central nervous system causes neurodegeneration in mice
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Chemical inhibitor of nonapoptotic cell death with therapeutic potential for ischemic brain injury
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Self-citationInhibition of Autophagy Prevents Hippocampal Pyramidal Neuron Death after Hypoxic-Ischemic Injury
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Tsc1 (hamartin) confers neuroprotection against ischemia by inducing autophagy
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Cited by
Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition) 1
Klionsky, D. J., Abdel-Aziz, A. K., Abdelfatah, S., Abdellatif, M., Abdoli, A., Abel, S., Abeliovich, H., Abildgaard, M. H., Abudu, Y. P., Acevedo-Arozena, A., et al. (2021) · Autophagy · doi:10.1080/15548627.2020.1797280 · Cited by 2,897
Self-citationSpinal Cord Injury: Pathophysiology, Multimolecular Interactions, and Underlying Recovery Mechanisms
Anjum, A., Yazid, M. D., Fauzi Daud, M., Idris, J., Ng, A. M. H., Selvi Naicker, A., Ismail, O. H. R., Athi Kumar, R. K., & Lokanathan, Y. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21207533 · Cited by 1,270
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Pharmacological modulation of autophagy: therapeutic potential and persisting obstacles
Galluzzi, L., Bravo-San Pedro, J. M., Levine, B., Green, D. R., & Kroemer, G. (2017) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2017.22 · Cited by 842
Cell Death Mechanisms in Stroke and Novel Molecular and Cellular Treatment Options
Sekerdag, E., Solaroglu, I., & Gursoy-Ozdemir, Y. (2018) · Current Neuropharmacology · doi:10.2174/1570159x16666180302115544 · Cited by 369
Metadata
- Authors
- Ginet, V., Spiehlmann, A., Rummel, C., Rudinskiy, N., Grishchuk, Y., Luthi-Carter, R., Clarke, P. G., Truttmann, A. C., & Puyal, J.
- Venue
- Autophagy
- Publisher
- Informa UK Limited
- Published
- 2014-03-11
- Volume
- 10
- Issue
- 5
- Pages
- 846-860
- ISSN
- 1554-8627 (ISSN-L)
- 1554-8635
- OpenAlex
- W2090831757
- Cited by
- 159
- References
- 10
- FWCI
- 10.56
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Ginet, V., Spiehlmann, A., Rummel, C., Rudinskiy, N., Grishchuk, Y., Luthi-Carter, R., Clarke, P. G., Truttmann, A. C., & Puyal, J. (2014). Involvement of autophagy in hypoxic-excitotoxic neuronal death. Autophagy. https://doi.org/10.4161/auto.28264
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