Limits...
Glutathione Peroxidase 4 is associated with Neuromelanin in Substantia Nigra and Dystrophic Axons in Putamen of Parkinson's brain.

Bellinger FP, Bellinger MT, Seale LA, Takemoto AS, Raman AV, Miki T, Manning-Boğ AB, Berry MJ, White LR, Ross GW - Mol Neurodegener (2011)

Bottom Line: Overall GPX4 was significantly reduced in substantia nigra in Parkinson's vs. control subjects, but was increased relative to the cell density of surviving nigral cells.In putamen, GPX4 was concentrated within dystrophic dopaminergic axons in Parkinson's subjects, although overall levels of GPX4 were not significantly different compared to control putamen.Additionally, our findings suggest this enzyme may contribute to the production of neuromelanin.

View Article: PubMed Central - HTML - PubMed

Affiliation: Cell and Molecular Biology Department, John A, Burns School of Medicine, University of Hawaii, Honolulu, HI 96813 USA. fb@hawaii.edu.

ABSTRACT

Background: Parkinson's disease is a neurodegenerative disorder characterized pathologically by the loss of nigrostriatal dopamine neurons that project from the substantia nigra in the midbrain to the putamen and caudate nuclei, leading to the clinical features of bradykinesia, rigidity, and rest tremor. Oxidative stress from oxidized dopamine and related compounds may contribute to the degeneration characteristic of this disease.

Results: To investigate a possible role of the phospholipid hydroperoxidase glutathione peroxidase 4 (GPX4) in protection from oxidative stress, we investigated GPX4 expression in postmortem human brain tissue from individuals with and without Parkinson's disease. In both control and Parkinson's samples, GPX4 was found in dopaminergic nigral neurons colocalized with neuromelanin. Overall GPX4 was significantly reduced in substantia nigra in Parkinson's vs. control subjects, but was increased relative to the cell density of surviving nigral cells. In putamen, GPX4 was concentrated within dystrophic dopaminergic axons in Parkinson's subjects, although overall levels of GPX4 were not significantly different compared to control putamen.

Conclusions: This study demonstrates an up-regulation of GPX4 in neurons of substantia nigra and association of this protein with dystrophic axons in striatum of Parkinson's brain, indicating a possible neuroprotective role. Additionally, our findings suggest this enzyme may contribute to the production of neuromelanin.

No MeSH data available.


Related in: MedlinePlus

GPX4 is reduced overall but increased relative to cell density in PD SN. A. GPX4 (dark grey) is visibly reduced in SN of PD subjects (n = 12) compared to controls (n = 11). B. Total immunoreactivity of GPX4 is significantly reduced in SN of PD subjects compared to controls (P = 0.0398, Student's t-test). C. GPX4 immunoreactivity is increased relative to cell density (P = 0.0192, Student's t-test). Scale bars: 20 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3037910&req=5

Figure 4: GPX4 is reduced overall but increased relative to cell density in PD SN. A. GPX4 (dark grey) is visibly reduced in SN of PD subjects (n = 12) compared to controls (n = 11). B. Total immunoreactivity of GPX4 is significantly reduced in SN of PD subjects compared to controls (P = 0.0398, Student's t-test). C. GPX4 immunoreactivity is increased relative to cell density (P = 0.0192, Student's t-test). Scale bars: 20 μm.

Mentions: We investigated possible changes in GPX4 in PD brain by measuring area of immunoreactivity using unbiased stereology. Using a Cavalieri probe, we determined that GPX4 was significantly decreased in SN of PD brain compared with control SN (Figure 4A, B). The total volume fraction of GPX4 immunoreactivity in this region was reduced by nearly one third in PD brain, from 0.036 ± 0.004 in control SN (n = 11) to 0.024 ± 0.003 in PD SN (n = 12).


Glutathione Peroxidase 4 is associated with Neuromelanin in Substantia Nigra and Dystrophic Axons in Putamen of Parkinson's brain.

Bellinger FP, Bellinger MT, Seale LA, Takemoto AS, Raman AV, Miki T, Manning-Boğ AB, Berry MJ, White LR, Ross GW - Mol Neurodegener (2011)

GPX4 is reduced overall but increased relative to cell density in PD SN. A. GPX4 (dark grey) is visibly reduced in SN of PD subjects (n = 12) compared to controls (n = 11). B. Total immunoreactivity of GPX4 is significantly reduced in SN of PD subjects compared to controls (P = 0.0398, Student's t-test). C. GPX4 immunoreactivity is increased relative to cell density (P = 0.0192, Student's t-test). Scale bars: 20 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3037910&req=5

Figure 4: GPX4 is reduced overall but increased relative to cell density in PD SN. A. GPX4 (dark grey) is visibly reduced in SN of PD subjects (n = 12) compared to controls (n = 11). B. Total immunoreactivity of GPX4 is significantly reduced in SN of PD subjects compared to controls (P = 0.0398, Student's t-test). C. GPX4 immunoreactivity is increased relative to cell density (P = 0.0192, Student's t-test). Scale bars: 20 μm.
Mentions: We investigated possible changes in GPX4 in PD brain by measuring area of immunoreactivity using unbiased stereology. Using a Cavalieri probe, we determined that GPX4 was significantly decreased in SN of PD brain compared with control SN (Figure 4A, B). The total volume fraction of GPX4 immunoreactivity in this region was reduced by nearly one third in PD brain, from 0.036 ± 0.004 in control SN (n = 11) to 0.024 ± 0.003 in PD SN (n = 12).

Bottom Line: Overall GPX4 was significantly reduced in substantia nigra in Parkinson's vs. control subjects, but was increased relative to the cell density of surviving nigral cells.In putamen, GPX4 was concentrated within dystrophic dopaminergic axons in Parkinson's subjects, although overall levels of GPX4 were not significantly different compared to control putamen.Additionally, our findings suggest this enzyme may contribute to the production of neuromelanin.

View Article: PubMed Central - HTML - PubMed

Affiliation: Cell and Molecular Biology Department, John A, Burns School of Medicine, University of Hawaii, Honolulu, HI 96813 USA. fb@hawaii.edu.

ABSTRACT

Background: Parkinson's disease is a neurodegenerative disorder characterized pathologically by the loss of nigrostriatal dopamine neurons that project from the substantia nigra in the midbrain to the putamen and caudate nuclei, leading to the clinical features of bradykinesia, rigidity, and rest tremor. Oxidative stress from oxidized dopamine and related compounds may contribute to the degeneration characteristic of this disease.

Results: To investigate a possible role of the phospholipid hydroperoxidase glutathione peroxidase 4 (GPX4) in protection from oxidative stress, we investigated GPX4 expression in postmortem human brain tissue from individuals with and without Parkinson's disease. In both control and Parkinson's samples, GPX4 was found in dopaminergic nigral neurons colocalized with neuromelanin. Overall GPX4 was significantly reduced in substantia nigra in Parkinson's vs. control subjects, but was increased relative to the cell density of surviving nigral cells. In putamen, GPX4 was concentrated within dystrophic dopaminergic axons in Parkinson's subjects, although overall levels of GPX4 were not significantly different compared to control putamen.

Conclusions: This study demonstrates an up-regulation of GPX4 in neurons of substantia nigra and association of this protein with dystrophic axons in striatum of Parkinson's brain, indicating a possible neuroprotective role. Additionally, our findings suggest this enzyme may contribute to the production of neuromelanin.

No MeSH data available.


Related in: MedlinePlus