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Increased Plasma Heme Oxygenase-1 Levels in Patients With Early-Stage Parkinson’s Disease

Introduction: Heme oxygenase-1 (HO-1) is a 32 kDa stress-response protein implicated in the pathogenesis of Parkinson’s disease (PD). Biliverdin is derived from heme through a reaction mediated by HO-1 and protects cells from oxidative stress. However, iron and carbon monoxide produced by the catabo...

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Autores principales: Sun, Wenhua, Zheng, Jinhua, Ma, Jianjun, Wang, Zhidong, Shi, Xiaoxue, Li, Mingjian, Huang, Shen, Hu, Shiyu, Zhao, Zhenxiang, Li, Dongsheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7906968/
https://www.ncbi.nlm.nih.gov/pubmed/33643023
http://dx.doi.org/10.3389/fnagi.2021.621508
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author Sun, Wenhua
Zheng, Jinhua
Ma, Jianjun
Wang, Zhidong
Shi, Xiaoxue
Li, Mingjian
Huang, Shen
Hu, Shiyu
Zhao, Zhenxiang
Li, Dongsheng
author_facet Sun, Wenhua
Zheng, Jinhua
Ma, Jianjun
Wang, Zhidong
Shi, Xiaoxue
Li, Mingjian
Huang, Shen
Hu, Shiyu
Zhao, Zhenxiang
Li, Dongsheng
author_sort Sun, Wenhua
collection PubMed
description Introduction: Heme oxygenase-1 (HO-1) is a 32 kDa stress-response protein implicated in the pathogenesis of Parkinson’s disease (PD). Biliverdin is derived from heme through a reaction mediated by HO-1 and protects cells from oxidative stress. However, iron and carbon monoxide produced by the catabolism of HO-1 exert detrimental effects on patients with PD. The purpose of this study was to determine whether plasma HO-1 levels represent a biomarker of PD and to further explore the underlying mechanism of increased HO-1 levels by applying voxel-based morphometry (VBM).Methods: We measured plasma HO-1 levels using an enzyme-linked immunosorbent assay (ELISA) in 156 subjects, including 81 patients with early- and advanced-stage PD and 75 subjects without PD. The analyses were adjusted to control for confounders such as age, sex, and medication. We analyzed T1-weighted magnetic resonance imaging (MRI) data from 74 patients with PD using VBM to elucidate the association between altered brain volumes and HO-1 levels. Then, we compared performance on MMSE sub-items between PD patients with low and high levels of HO-1 using Mann-Whitney U tests.Results: Plasma HO-1 levels were significantly elevated in PD patients, predominantly those with early-stage PD, compared with controls (p < 0.05). The optimal cutoff value for patients with early PD was 2.245 ng/ml HO-1 [area under the curve (AUC) = 0.654]. Plasma HO-1 levels were unaffected by sex, age, and medications (p > 0.05). The right hippocampal volume was decreased in the subset of PD patients with high HO-1 levels (p < 0.05). A weak correlation was observed between right hippocampal volume and plasma HO-1 levels (r = −0.273, p = 0.018). There was no difference in total MMSE scores between the low- and high-HO-1 groups (p > 0.05), but the high-HO-1 group had higher language scores than the low-HO-1 group (p < 0.05).Conclusions: Plasma HO-1 levels may be a promising biomarker of early PD. Moreover, a high plasma concentration of the HO-1 protein is associated with a reduction in right hippocampal volume.
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spelling pubmed-79069682021-02-27 Increased Plasma Heme Oxygenase-1 Levels in Patients With Early-Stage Parkinson’s Disease Sun, Wenhua Zheng, Jinhua Ma, Jianjun Wang, Zhidong Shi, Xiaoxue Li, Mingjian Huang, Shen Hu, Shiyu Zhao, Zhenxiang Li, Dongsheng Front Aging Neurosci Neuroscience Introduction: Heme oxygenase-1 (HO-1) is a 32 kDa stress-response protein implicated in the pathogenesis of Parkinson’s disease (PD). Biliverdin is derived from heme through a reaction mediated by HO-1 and protects cells from oxidative stress. However, iron and carbon monoxide produced by the catabolism of HO-1 exert detrimental effects on patients with PD. The purpose of this study was to determine whether plasma HO-1 levels represent a biomarker of PD and to further explore the underlying mechanism of increased HO-1 levels by applying voxel-based morphometry (VBM).Methods: We measured plasma HO-1 levels using an enzyme-linked immunosorbent assay (ELISA) in 156 subjects, including 81 patients with early- and advanced-stage PD and 75 subjects without PD. The analyses were adjusted to control for confounders such as age, sex, and medication. We analyzed T1-weighted magnetic resonance imaging (MRI) data from 74 patients with PD using VBM to elucidate the association between altered brain volumes and HO-1 levels. Then, we compared performance on MMSE sub-items between PD patients with low and high levels of HO-1 using Mann-Whitney U tests.Results: Plasma HO-1 levels were significantly elevated in PD patients, predominantly those with early-stage PD, compared with controls (p < 0.05). The optimal cutoff value for patients with early PD was 2.245 ng/ml HO-1 [area under the curve (AUC) = 0.654]. Plasma HO-1 levels were unaffected by sex, age, and medications (p > 0.05). The right hippocampal volume was decreased in the subset of PD patients with high HO-1 levels (p < 0.05). A weak correlation was observed between right hippocampal volume and plasma HO-1 levels (r = −0.273, p = 0.018). There was no difference in total MMSE scores between the low- and high-HO-1 groups (p > 0.05), but the high-HO-1 group had higher language scores than the low-HO-1 group (p < 0.05).Conclusions: Plasma HO-1 levels may be a promising biomarker of early PD. Moreover, a high plasma concentration of the HO-1 protein is associated with a reduction in right hippocampal volume. Frontiers Media S.A. 2021-02-12 /pmc/articles/PMC7906968/ /pubmed/33643023 http://dx.doi.org/10.3389/fnagi.2021.621508 Text en Copyright © 2021 Sun, Zheng, Ma, Wang, Shi, Li, Huang, Hu, Zhao and Li. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Sun, Wenhua
Zheng, Jinhua
Ma, Jianjun
Wang, Zhidong
Shi, Xiaoxue
Li, Mingjian
Huang, Shen
Hu, Shiyu
Zhao, Zhenxiang
Li, Dongsheng
Increased Plasma Heme Oxygenase-1 Levels in Patients With Early-Stage Parkinson’s Disease
title Increased Plasma Heme Oxygenase-1 Levels in Patients With Early-Stage Parkinson’s Disease
title_full Increased Plasma Heme Oxygenase-1 Levels in Patients With Early-Stage Parkinson’s Disease
title_fullStr Increased Plasma Heme Oxygenase-1 Levels in Patients With Early-Stage Parkinson’s Disease
title_full_unstemmed Increased Plasma Heme Oxygenase-1 Levels in Patients With Early-Stage Parkinson’s Disease
title_short Increased Plasma Heme Oxygenase-1 Levels in Patients With Early-Stage Parkinson’s Disease
title_sort increased plasma heme oxygenase-1 levels in patients with early-stage parkinson’s disease
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7906968/
https://www.ncbi.nlm.nih.gov/pubmed/33643023
http://dx.doi.org/10.3389/fnagi.2021.621508
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