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Alterations in glutathione S-transferase pi expression following exposure to MPP+-induced oxidative stress in the blood of Parkinson’s disease patients

https://doi.org/10.1016/j.parkreldis.2011.06.026Get rights and content

Abstract

The major motor symptoms of Parkinson’s disease do not occur until a majority of the dopaminergic neurons in the midbrain SNpc have already died. For this reason, it is critical to identify biomarkers that will allow for the identification of presymptomatic individuals. In this study, we examine the baseline expression of the anti-oxidant protein glutathione S-transferase pi (GSTpi) in the blood of PD patients and environmentally- and age-matched controls and compare it to GSTpi levels following exposure to 1-methyl-4-phenylpyridinium (MPP+), an agent that has been shown to induce oxidative stress. We find that after 4 h of exposure to MPP+, significant increases in GSTpi levels can be observed in the leukocytes of PD patients. No changes were seen in other blood components. This suggests that GSTpi and potentially other members of this and other anti-oxidant families may be viable biomarkers for PD.

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Methods

Seventeen patients with PD (12 men, age 68 ± 9.4; 5 women, age 71 ± 10, range 51–81), and seventeen age-matched controls (12 women, age 66 ± 2.7; 5 men, age 66 ± 6.4, range 49–78) took part in the study. PD patients were at least stage II PD on the Hoehn and Yahr scale and were currently taking levodopa/carbidopa (with the exception of 1), and anti-inflammatory and/or anti-oxidant drugs (See Table 1). The study was performed at St. Jude Children’s Research Hospital in collaboration with the

Results

Examination of baseline GSTpi levels in whole blood, erythrocytes or leukocytes of PD patients, compared with their environmentally- and age-matched controls, demonstrated no differences (data not shown). To determine if GSTpi levels of PD patients reacted differently to oxidative stress, either 5 or 10 μM MPP+, an agent shown to induce parkinsonism in humans and mice through generation of oxidative stress (Supplementary Ref. 5) was added to the blood samples, and GSTpi expression was measured

Discussion

Parkinson’s disease generally develops in the 6th decade of life, and symptoms appear only after significant damage has already occurred in the basal ganglia. For this reason, the identification and development of biomarkers that predict who is at risk for developing the disease, at a time prior to the occurrence of these pathological events, would potentially have a significant impact on disease progression and management. At this time, only 1 biomarker has been approved for clinical use,

Acknowledgments

This work is supported by NS039006 (to RJS) and the American Lebanese Syrian Associated Charities (ALSAC).

References (12)

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Cited by (12)

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    Recent evidence showed that peripheral mitochondrial function in platelets and white blood cells (lymphocytes) is consistently impaired in PD patients compared to controls [16–18]. and that the erythrocytes of PD patients tend to undergo eryptosis [19] due to excessive oxidative stress [20], resulting in the decline of Hb levels. Systemic iron metabolism has also been investigated, and several studies found a protective effect of high serum iron levels on PD [21–23] and even on disease severity in patients with PD [24].

  • Changes in blood anti-oxidation enzyme levels in MPTP-treated monkeys

    2017, Neuroscience Letters
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    By systemic administration, the brain’s SN suffers from symmetrical injury, and this progression is similar to that in humans. According to clinical studies, parkinson’s symptoms may appear in different places such as the upper limb [2], lower limb [20] or equally in the upper and lower limbs [21]. In our study, most symptoms initially appeared in the upper limb.

  • Glutathione metabolism and Parkinson's disease

    2013, Free Radical Biology and Medicine
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    Maarouf et al. [223], also using a proteomic analysis, examined postmortem ventricular cerebrospinal fluid from PD patients and found a significant increase in GST Pi. Recently, Korff et al. [224] measured changes in GST Pi protein in blood, comparing GST Pi levels at baseline and at various times after addition of MPP+ as an inducer of oxidative stress. They demonstrated that 4 h after MPP+, GST Pi is significantly increased in the white blood cells of PD patients compared to control subjects, whereas no changes are seen when examining whole blood, plasma, or the red cell fraction.

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The review of this paper was entirely handled by an Associate Editor, R.L. Rodnitzky.

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