The Potential Role of Peripheral Oxidative Stress on the Neurovascular Unit in Amyotrophic Lateral Sclerosis Pathogenesis: A Preliminary Report from Human and In Vitro Evaluations
Oxidative stress, the alteration of mitochondrial function, and changes in the neurovascular unit (NVU) could play a role in Amyotrophic Lateral Sclerosis (ALS) pathogenesis. Our aim was to analyze the plasma redox system and nitric oxide (NO) in 25 ALS new-diagnosed patients and five healthy contro...
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2022-03-01
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author | Elena Grossini Divya Garhwal Sakthipriyan Venkatesan Daniela Ferrante Angelica Mele Massimo Saraceno Ada Scognamiglio Jessica Mandrioli Amedeo Amedei Fabiola De Marchi Letizia Mazzini |
author_facet | Elena Grossini Divya Garhwal Sakthipriyan Venkatesan Daniela Ferrante Angelica Mele Massimo Saraceno Ada Scognamiglio Jessica Mandrioli Amedeo Amedei Fabiola De Marchi Letizia Mazzini |
author_sort | Elena Grossini |
collection | DOAJ |
description | Oxidative stress, the alteration of mitochondrial function, and changes in the neurovascular unit (NVU) could play a role in Amyotrophic Lateral Sclerosis (ALS) pathogenesis. Our aim was to analyze the plasma redox system and nitric oxide (NO) in 25 ALS new-diagnosed patients and five healthy controls and the effects of plasma on the peroxidation/mitochondrial function in human umbilical cord-derived endothelial vascular cells (HUVEC) and astrocytes. In plasma, thiobarbituric acid reactive substances (TBARS), glutathione (GSH), and nitric oxide (NO) were analyzed by using specific assays. In HUVEC/astrocytes, the effects of plasma on the release of mitochondrial reactive oxygen species (mitoROS) and NO, viability, and mitochondrial membrane potential were investigated. In the plasma of ALS patients, an increase in TBARS and a reduction in GSH and NO were found. In HUVEC/astrocytes treated with a plasma of ALS patients, mitoROS increased, whereas cell viability and mitochondrial membrane potential decreased. Our results show that oxidative stress and NVU play a central role in ALS and suggest that unknown plasma factors could be involved in the disease pathogenesis. Quantifiable changes in ALS plasma related to redox state alterations can possibly be used for early diagnosis. |
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language | English |
last_indexed | 2024-03-09T20:04:51Z |
publishDate | 2022-03-01 |
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spelling | doaj.art-76877be705934cd4b0c5e85248b0a8f42023-11-24T00:33:44ZengMDPI AGBiomedicines2227-90592022-03-0110369110.3390/biomedicines10030691The Potential Role of Peripheral Oxidative Stress on the Neurovascular Unit in Amyotrophic Lateral Sclerosis Pathogenesis: A Preliminary Report from Human and In Vitro EvaluationsElena Grossini0Divya Garhwal1Sakthipriyan Venkatesan2Daniela Ferrante3Angelica Mele4Massimo Saraceno5Ada Scognamiglio6Jessica Mandrioli7Amedeo Amedei8Fabiola De Marchi9Letizia Mazzini10Laboratory of Physiology, Department of Translational Medicine, University East Piedmont, 28100 Novara, ItalyLaboratory of Physiology, Department of Translational Medicine, University East Piedmont, 28100 Novara, ItalyLaboratory of Physiology, Department of Translational Medicine, University East Piedmont, 28100 Novara, ItalyStatistic Unit, Department of Translational Medicine, University East Piedmont, 28100 Novara, ItalyALS Center, Neurology Unit, Department of Translational Medicine, University East Piedmont, 28100 Novara, ItalyALS Center, Neurology Unit, Department of Translational Medicine, University East Piedmont, 28100 Novara, ItalyALS Center, Neurology Unit, Department of Translational Medicine, University East Piedmont, 28100 Novara, ItalyDepartment of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, 41125 Modena, ItalyDepartment of Experimental and Clinical Medicine, University of Florence, 50134 Florence, ItalyALS Center, Neurology Unit, Department of Translational Medicine, University East Piedmont, 28100 Novara, ItalyALS Center, Neurology Unit, Department of Translational Medicine, University East Piedmont, 28100 Novara, ItalyOxidative stress, the alteration of mitochondrial function, and changes in the neurovascular unit (NVU) could play a role in Amyotrophic Lateral Sclerosis (ALS) pathogenesis. Our aim was to analyze the plasma redox system and nitric oxide (NO) in 25 ALS new-diagnosed patients and five healthy controls and the effects of plasma on the peroxidation/mitochondrial function in human umbilical cord-derived endothelial vascular cells (HUVEC) and astrocytes. In plasma, thiobarbituric acid reactive substances (TBARS), glutathione (GSH), and nitric oxide (NO) were analyzed by using specific assays. In HUVEC/astrocytes, the effects of plasma on the release of mitochondrial reactive oxygen species (mitoROS) and NO, viability, and mitochondrial membrane potential were investigated. In the plasma of ALS patients, an increase in TBARS and a reduction in GSH and NO were found. In HUVEC/astrocytes treated with a plasma of ALS patients, mitoROS increased, whereas cell viability and mitochondrial membrane potential decreased. Our results show that oxidative stress and NVU play a central role in ALS and suggest that unknown plasma factors could be involved in the disease pathogenesis. Quantifiable changes in ALS plasma related to redox state alterations can possibly be used for early diagnosis.https://www.mdpi.com/2227-9059/10/3/691astrocytesendothelial cellsmitochondrianitric oxideoxidative stress |
spellingShingle | Elena Grossini Divya Garhwal Sakthipriyan Venkatesan Daniela Ferrante Angelica Mele Massimo Saraceno Ada Scognamiglio Jessica Mandrioli Amedeo Amedei Fabiola De Marchi Letizia Mazzini The Potential Role of Peripheral Oxidative Stress on the Neurovascular Unit in Amyotrophic Lateral Sclerosis Pathogenesis: A Preliminary Report from Human and In Vitro Evaluations Biomedicines astrocytes endothelial cells mitochondria nitric oxide oxidative stress |
title | The Potential Role of Peripheral Oxidative Stress on the Neurovascular Unit in Amyotrophic Lateral Sclerosis Pathogenesis: A Preliminary Report from Human and In Vitro Evaluations |
title_full | The Potential Role of Peripheral Oxidative Stress on the Neurovascular Unit in Amyotrophic Lateral Sclerosis Pathogenesis: A Preliminary Report from Human and In Vitro Evaluations |
title_fullStr | The Potential Role of Peripheral Oxidative Stress on the Neurovascular Unit in Amyotrophic Lateral Sclerosis Pathogenesis: A Preliminary Report from Human and In Vitro Evaluations |
title_full_unstemmed | The Potential Role of Peripheral Oxidative Stress on the Neurovascular Unit in Amyotrophic Lateral Sclerosis Pathogenesis: A Preliminary Report from Human and In Vitro Evaluations |
title_short | The Potential Role of Peripheral Oxidative Stress on the Neurovascular Unit in Amyotrophic Lateral Sclerosis Pathogenesis: A Preliminary Report from Human and In Vitro Evaluations |
title_sort | potential role of peripheral oxidative stress on the neurovascular unit in amyotrophic lateral sclerosis pathogenesis a preliminary report from human and in vitro evaluations |
topic | astrocytes endothelial cells mitochondria nitric oxide oxidative stress |
url | https://www.mdpi.com/2227-9059/10/3/691 |
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