Evaluation of salivary heme oxygenase-1 as a potential biomarker of early Parkinson's disease

Herp is an endoplasmic reticulum- (ER-) resident membrane protein that plays a role in ER-associated degradation. We studied the expression of Herp and its effect on neurodegeneration in a mouse model of Parkinson’s disease (PD), in which both the oxidative stress and the ER stress are evoked. Eight hours after administering a PD-related neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), to mice, the expression of Herp increased at both the mRNA and the protein levels. Experiments usingHerpud1+/+andHerpud1−/−mice revealed that the status of acute degeneration of nigrostriatal neurons and reactive astrogliosis was comparable between two genotypes after MPTP injection. However, the expression of a potent antioxidant, heme oxygenase-1 (HO-1), was detected to a higher degree in the astrocytes ofHerpud1−/−mice than in the astrocytes ofHerpud1+/+mice 24 h after MPTP administration. Further experiments using cultured astrocytes revealed that the stress response against MPP+, an active form of MPTP, and hydrogen peroxide, both of which cause oxidative stress, was comparable between the two genotypes. These results suggest that deletion ofHerpud1may cause a slightly higher level of initial damage in the nigrastrial neurons after MPTP administration but is compensated for by higher induction of antioxidants such as HO-1 in astrocytes.

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

Frontiers in Aging Neuroscience ◽

10.3389/fnagi.2021.621508 ◽

2021 ◽

Vol 13 ◽

Author(s):

Wenhua Sun ◽

Jinhua Zheng ◽

Jianjun Ma ◽

Zhidong Wang ◽

Xiaoxue Shi ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Heme Oxygenase ◽

Early Stage ◽

Area Under The Curve ◽

Underlying Mechanism ◽

Hippocampal Volume ◽

Enzyme Linked Immunosorbent Assay ◽

Heme Oxygenase 1 ◽

Brain Volumes

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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Neural Heme Oxygenase-1 Expression in Idiopathic Parkinson's Disease

Experimental Neurology ◽

10.1006/exnr.1997.6752 ◽

1998 ◽

Vol 150 (1) ◽

pp. 60-68 ◽

Cited By ~ 204

Author(s):

H.M. Schipper ◽

A. Liberman ◽

E.G. Stopa

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Heme Oxygenase ◽

Heme Oxygenase 1 ◽

Idiopathic Parkinson’S Disease ◽

Idiopathic Parkinson's Disease

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Elevated Heme Oxygenase-1 Correlates With Increased Brain Iron Deposition Measured by Quantitative Susceptibility Mapping and Decreased Hemoglobin in Patients With Parkinson’s Disease

Frontiers in Aging Neuroscience ◽

10.3389/fnagi.2021.656626 ◽

2021 ◽

Vol 13 ◽

Author(s):

Jinghui Xu ◽

Chi Xiao ◽

Weizheng Song ◽

Xiangqin Cui ◽

Mengqiu Pan ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Heme Oxygenase ◽

Human Subjects ◽

Susceptibility Mapping ◽

Iron Deposition ◽

Heme Oxygenase 1 ◽

Brain Iron ◽

Quantitative Susceptibility Mapping ◽

Brain Iron Deposition

Background: Brain iron deposition, low hemoglobin (HGB), and increased heme oxygenase-1 (HO-1) have been implicated in Parkinson’s disease (PD). However, the association among them in PD is poorly studied.Objective: To explore the association of the level of HO-1 with brain iron deposition and low level of HGB in PD.Methods: A total of 32 patients with PD and 26 controls were recruited for this study. C57BL/6 male mice were used in generating 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced chronic PD model. The Levels of serum HO-1 and HGB of human subjects and mice were assayed by ELISA, blood routine test, respectively. Quantitative susceptibility mapping (QSM) was used to quantitatively analyze brain iron deposition in human subjects and mice. HO-1 inhibitor (Sn-protoporphyrin, SnPP) was used to suppress the function and expression of HO-1 in PD mice. Correlations between the concentration of serum HO-1 and iron deposition of the region of interests (ROIs), levels of HGB, between the three factors mentioned above, and scores of clinical scales were explored in PD patients.Results: This study revealed significant elevation of the serum HO-1 concentration, iron deposition within bilateral substantial nigra (SN), red nucleus (RN), and putamen (PUT) and decrease of HGB level in PD patients. There was a significantly positive correlation between the serum HO-1 concentration and iron deposition within SN, an inverse correlation between the serum HO-1 concentration and HGB level in PD patients. A significant increase in HO-1 expression of serum and iron deposition in SN was also observed in the PD mouse model, and the SnPP could significantly reduce iron deposition in the SN.Conclusions: The high level of HO-1 may be the common mechanism of iron deposition and low HGB in PD. Therefore, the findings presented in this study indicate that HO-1 correlates with brain iron deposition and anemia in PD.

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