The Autophagy-Related Organelle Autophagoproteasome Is Suppressed within Ischemic Penumbra

The peri-infarct region, which surrounds the irreversible ischemic stroke area is named ischemic penumbra. This term emphasizes the borderline conditions for neurons placed within such a critical region. Area penumbra separates the ischemic core, where frank cell loss occurs, from the surrounding he...

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Published in:International journal of molecular sciences 2021-10, Vol.22 (19), p.10364
Main Authors: Biagioni, Francesca, Mastroiacovo, Federica, Lenzi, Paola, Puglisi-Allegra, Stefano, Busceti, Carla L., Ryskalin, Larisa, Ferese, Rosangela, Bucci, Domenico, Frati, Alessandro, Nicoletti, Ferdinando, Fornai, Francesco
Format: Article
Language:English
Subjects:
Autophagy
autophagy vacuoles
Biochemical markers
Clearing
heat shock protein 70 (HSP70)
Heat shock proteins
Hsp70 protein
Ischemia
LC3
Localization
Magnetic resonance imaging
Metabolism
Microscopy
Neurons
Overexpression
P20S
Phagocytosis
proteasome
Proteins
ultrastructural morphometry
Vacuoles
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Summary:The peri-infarct region, which surrounds the irreversible ischemic stroke area is named ischemic penumbra. This term emphasizes the borderline conditions for neurons placed within such a critical region. Area penumbra separates the ischemic core, where frank cell loss occurs, from the surrounding healthy brain tissue. Within such a brain region, nervous matter, and mostly neurons are impaired concerning metabolic conditions. The classic biochemical marker, which reliably marks area penumbra is the over-expression of the heat shock protein 70 (HSP70). However, other proteins related to cell clearing pathways are modified within area penumbra. Among these, autophagy proteins like LC3 increase in a way, which recapitulates Hsp70. In contrast, components, such as P20S, markedly decrease. Despite apparent discrepancies, the present study indicates remarkable overlapping between LC3 and P20S redistribution within area penumbra. In fact, the amount of both proteins is markedly reduced within vacuoles. Specifically, a massive loss of LC3 + P20S immuno-positive vacuoles (autophagoproteasomes) is reported here. This represents the most relevant sub-cellular alteration here described in cell clearing pathways within area penumbra. The functional significance of these findings remains to be determined and it will take a novel experimental stream to decipher the fine-tuning of such a phenomenon.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms221910364