Resveratrol Preconditioning Downregulates PARP1 Protein to Alleviate PARP1-Mediated Cell Death Following Cerebral Ischemia.

Autor: Jackson CW; Peritz Scheinberg Cerebral Vascular Disease Research Laboratories, University of Miami Leonard M. Miller School of Medicine, Miami, FL, 33136, USA.; Department of Neurology, University of Miami Leonard M. Miller School of Medicine, PO Box 016960, Miami, FL, 33136, USA.; Neuroscience Program, University of Miami Leonard M. Miller School of Medicine, Miami, FL, USA., Xu J; Peritz Scheinberg Cerebral Vascular Disease Research Laboratories, University of Miami Leonard M. Miller School of Medicine, Miami, FL, 33136, USA.; Department of Neurology, University of Miami Leonard M. Miller School of Medicine, PO Box 016960, Miami, FL, 33136, USA.; Neuroscience Program, University of Miami Leonard M. Miller School of Medicine, Miami, FL, USA., Escobar I; Peritz Scheinberg Cerebral Vascular Disease Research Laboratories, University of Miami Leonard M. Miller School of Medicine, Miami, FL, 33136, USA.; Department of Neurology, University of Miami Leonard M. Miller School of Medicine, PO Box 016960, Miami, FL, 33136, USA.; Neuroscience Program, University of Miami Leonard M. Miller School of Medicine, Miami, FL, USA., Saul I; Peritz Scheinberg Cerebral Vascular Disease Research Laboratories, University of Miami Leonard M. Miller School of Medicine, Miami, FL, 33136, USA.; Department of Neurology, University of Miami Leonard M. Miller School of Medicine, PO Box 016960, Miami, FL, 33136, USA., Fagerli E; Peritz Scheinberg Cerebral Vascular Disease Research Laboratories, University of Miami Leonard M. Miller School of Medicine, Miami, FL, 33136, USA.; Department of Neurology, University of Miami Leonard M. Miller School of Medicine, PO Box 016960, Miami, FL, 33136, USA.; Neuroscience Program, University of Miami Leonard M. Miller School of Medicine, Miami, FL, USA., Dave KR; Peritz Scheinberg Cerebral Vascular Disease Research Laboratories, University of Miami Leonard M. Miller School of Medicine, Miami, FL, 33136, USA.; Department of Neurology, University of Miami Leonard M. Miller School of Medicine, PO Box 016960, Miami, FL, 33136, USA.; Neuroscience Program, University of Miami Leonard M. Miller School of Medicine, Miami, FL, USA., Perez-Pinzon MA; Peritz Scheinberg Cerebral Vascular Disease Research Laboratories, University of Miami Leonard M. Miller School of Medicine, Miami, FL, 33136, USA. perezpinzon@med.miami.edu.; Department of Neurology, University of Miami Leonard M. Miller School of Medicine, PO Box 016960, Miami, FL, 33136, USA. perezpinzon@med.miami.edu.; Neuroscience Program, University of Miami Leonard M. Miller School of Medicine, Miami, FL, USA. perezpinzon@med.miami.edu.
Jazyk: angličtina
Zdroj: Translational stroke research [Transl Stroke Res] 2024 Feb; Vol. 15 (1), pp. 165-178. Date of Electronic Publication: 2023 Jan 12.
DOI: 10.1007/s12975-022-01119-z
Abstrakt: Stroke remains a leading cause of mortality; however, available therapeutics are limited. The study of ischemic tolerance, in paradigms such as resveratrol preconditioning (RPC), provides promise for the development of novel prophylactic therapies. The heavily oxidative environment following stroke promotes poly-ADP-ribose polymerase 1 (PARP1)-overactivation and parthanatos, both of which are major contributors to neuronal injury. In this study, we tested the hypothesis that RPC instills ischemic tolerance through decreasing PARP1 overexpression and parthanatos following in vitro and in vivo cerebral ischemia. To test this hypothesis, we utilized rat primary neuronal cultures (PNCs) and middle cerebral artery occlusion (MCAO) in the rat as in vitro and in vivo models, respectively. RPC was administered 2 days preceding ischemic insults. RPC protected PNCs against oxygen and glucose deprivation (OGD)-induced neuronal loss, as well as increases in total PARP1 protein, implying protection against PARP1-overactivation. Twelve hours following OGD, we observed reductions in NAD + /NADH as well as an increase in AIF nuclear translocation, but RPC ameliorated NAD + /NADH loss and blocked AIF nuclear translocation. MCAO in the rat induced AIF nuclear translocation in the ischemic penumbra after 24 h, which was ameliorated with RPC. We tested the hypothesis that RPC's neuroprotection was instilled through long-term downregulation of nuclear PARP1 protein. RPC downregulated nuclear PARP1 protein for at least 6 days in PNCs, likely contributing to RPC's ischemic tolerance. This study describes a novel mechanism by which RPC instills prophylaxis against ischemia-induced PARP1 overexpression and parthanatos, through a long-term reduction of nuclear PARP1 protein.
(© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
Databáze: MEDLINE
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