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Article

The Autophagy-Related Organelle Autophagoproteasome Is Suppressed within Ischemic Penumbra

by
Francesca Biagioni
1,†,
Federica Mastroiacovo
1,†,
Paola Lenzi
2,†,
Stefano Puglisi-Allegra
1,
Carla L. Busceti
1,
Larisa Ryskalin
2,
Rosangela Ferese
1,
Domenico Bucci
1,
Alessandro Frati
1,3,
Ferdinando Nicoletti
1,4 and
Francesco Fornai
1,2,*
1
I.R.C.C.S. Neuromed, Via Atinense 18, 86077 Pozzilli, Italy
2
Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Via Roma 55, 56126 Pisa, Italy
3
Neurosurgery Division, Human Neurosciences Department, Sapienza University, 00135 Rome, Italy
4
Department of Physiology and Pharmacology “V. Erspamer”, University Sapienza of Rome, 00185 Rome, Italy
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Int. J. Mol. Sci. 2021, 22(19), 10364; https://doi.org/10.3390/ijms221910364
Submission received: 5 August 2021 / Revised: 22 September 2021 / Accepted: 24 September 2021 / Published: 26 September 2021
(This article belongs to the Special Issue Autophagy in Cell Survival and Death)
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Abstract

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.
Keywords: autophagy vacuoles; proteasome; LC3; P20S; heat shock protein 70 (HSP70); ultrastructural morphometry; stoichiometry; compartmentalization autophagy vacuoles; proteasome; LC3; P20S; heat shock protein 70 (HSP70); ultrastructural morphometry; stoichiometry; compartmentalization

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MDPI and ACS Style

Biagioni, F.; Mastroiacovo, F.; Lenzi, P.; Puglisi-Allegra, S.; Busceti, C.L.; Ryskalin, L.; Ferese, R.; Bucci, D.; Frati, A.; Nicoletti, F.; et al. The Autophagy-Related Organelle Autophagoproteasome Is Suppressed within Ischemic Penumbra. Int. J. Mol. Sci. 2021, 22, 10364. https://doi.org/10.3390/ijms221910364

AMA Style

Biagioni F, Mastroiacovo F, Lenzi P, Puglisi-Allegra S, Busceti CL, Ryskalin L, Ferese R, Bucci D, Frati A, Nicoletti F, et al. The Autophagy-Related Organelle Autophagoproteasome Is Suppressed within Ischemic Penumbra. International Journal of Molecular Sciences. 2021; 22(19):10364. https://doi.org/10.3390/ijms221910364

Chicago/Turabian Style

Biagioni, Francesca, Federica Mastroiacovo, Paola Lenzi, Stefano Puglisi-Allegra, Carla L. Busceti, Larisa Ryskalin, Rosangela Ferese, Domenico Bucci, Alessandro Frati, Ferdinando Nicoletti, and et al. 2021. "The Autophagy-Related Organelle Autophagoproteasome Is Suppressed within Ischemic Penumbra" International Journal of Molecular Sciences 22, no. 19: 10364. https://doi.org/10.3390/ijms221910364

APA Style

Biagioni, F., Mastroiacovo, F., Lenzi, P., Puglisi-Allegra, S., Busceti, C. L., Ryskalin, L., Ferese, R., Bucci, D., Frati, A., Nicoletti, F., & Fornai, F. (2021). The Autophagy-Related Organelle Autophagoproteasome Is Suppressed within Ischemic Penumbra. International Journal of Molecular Sciences, 22(19), 10364. https://doi.org/10.3390/ijms221910364

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