The Autophagy-Related Organelle Autophagoproteasome Is Suppressed within Ischemic Penumbra |
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Authors: | Francesca Biagioni Federica Mastroiacovo Paola Lenzi Stefano Puglisi-Allegra Carla L. Busceti Larisa Ryskalin Rosangela Ferese Domenico Bucci Alessandro Frati Ferdinando Nicoletti Francesco Fornai |
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Affiliation: | 1.I.R.C.C.S. Neuromed, Via Atinense 18, 86077 Pozzilli, Italy; (F.B.); (F.M.); (S.P.-A.); (C.L.B.); (R.F.); (D.B.); (A.F.); (F.N.);2.Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Via Roma 55, 56126 Pisa, Italy; (P.L.); (L.R.);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 |
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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. |
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Keywords: | autophagy vacuoles proteasome LC3 P20S heat shock protein 70 (HSP70) ultrastructural morphometry stoichiometry compartmentalization |
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