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Article

The Bacterial Toxin CNF1 Protects Human Neuroblastoma SH-SY5Y Cells against 6-Hydroxydopamine-Induced Cell Damage: The Hypothesis of CNF1-Promoted Autophagy as an Antioxidant Strategy

1
Istituto Superiore di Sanità, 00161 Rome, Italy
2
University of Bologna, 40126 Bologna, Italy
3
Association for Research on Integrative Oncology Therapies (ARTOI), 00165 Rome, Italy
*
Author to whom correspondence should be addressed.
Equal author contribution.
Principal investigators.
Int. J. Mol. Sci. 2020, 21(9), 3390; https://doi.org/10.3390/ijms21093390
Received: 6 April 2020 / Revised: 29 April 2020 / Accepted: 8 May 2020 / Published: 11 May 2020
(This article belongs to the Special Issue Bacterial Protein Toxins: Enemies within or Unexpected Friends 2.0)
Several chronic neuroinflammatory diseases, including Parkinson’s disease (PD), have the so-called ‘redox imbalance’ in common, a dynamic system modulated by various factors. Among them, alteration of the mitochondrial functionality can cause overproduction of reactive oxygen species (ROS) with the consequent induction of oxidative DNA damage and apoptosis. Considering the failure of clinical trials with drugs that eliminate ROS directly, research currently focuses on approaches that counteract redox imbalance, thus restoring normal physiology in a neuroinflammatory condition. Herein, we used SH-SY5Y cells treated with 6-hydroxydopamine (6-OHDA), a neurotoxin broadly employed to generate experimental models of PD. Cells were pre-treated with the Rho-modulating Escherichia coli cytotoxic necrotizing factor 1 (CNF1), before the addition of 6-OHDA. Then, cell viability, mitochondrial morphology and dynamics, redox profile as well as autophagic markers expression were assessed. We found that CNF1 preserves cell viability and counteracts oxidative stress induced by 6-OHDA. These effects are accompanied by modulation of the mitochondrial network and an increase in macroautophagic markers. Our results confirm the Rho GTPases as suitable pharmacological targets to counteract neuroinflammatory diseases and evidence the potentiality of CNF1, whose beneficial effects on pathological animal models have been already proven to act against oxidative stress through an autophagic strategy. View Full-Text
Keywords: 6-hydroxydopamine; mitochondria; cytotoxic necrotizing factor type 1; oxidative stress; reactive oxygen species; macroautophagy; Rho GTP-binding proteins 6-hydroxydopamine; mitochondria; cytotoxic necrotizing factor type 1; oxidative stress; reactive oxygen species; macroautophagy; Rho GTP-binding proteins
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MDPI and ACS Style

Travaglione, S.; Loizzo, S.; Vona, R.; Ballan, G.; Rivabene, R.; Giordani, D.; Guidotti, M.; Dupuis, M.L.; Maroccia, Z.; Baiula, M.; Rimondini, R.; Campana, G.; Fiorentini, C. The Bacterial Toxin CNF1 Protects Human Neuroblastoma SH-SY5Y Cells against 6-Hydroxydopamine-Induced Cell Damage: The Hypothesis of CNF1-Promoted Autophagy as an Antioxidant Strategy. Int. J. Mol. Sci. 2020, 21, 3390. https://doi.org/10.3390/ijms21093390

AMA Style

Travaglione S, Loizzo S, Vona R, Ballan G, Rivabene R, Giordani D, Guidotti M, Dupuis ML, Maroccia Z, Baiula M, Rimondini R, Campana G, Fiorentini C. The Bacterial Toxin CNF1 Protects Human Neuroblastoma SH-SY5Y Cells against 6-Hydroxydopamine-Induced Cell Damage: The Hypothesis of CNF1-Promoted Autophagy as an Antioxidant Strategy. International Journal of Molecular Sciences. 2020; 21(9):3390. https://doi.org/10.3390/ijms21093390

Chicago/Turabian Style

Travaglione, Sara, Stefano Loizzo, Rosa Vona, Giulia Ballan, Roberto Rivabene, Danila Giordani, Marco Guidotti, Maria L. Dupuis, Zaira Maroccia, Monica Baiula, Roberto Rimondini, Gabriele Campana, and Carla Fiorentini. 2020. "The Bacterial Toxin CNF1 Protects Human Neuroblastoma SH-SY5Y Cells against 6-Hydroxydopamine-Induced Cell Damage: The Hypothesis of CNF1-Promoted Autophagy as an Antioxidant Strategy" International Journal of Molecular Sciences 21, no. 9: 3390. https://doi.org/10.3390/ijms21093390

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