Glia Maturation Factor Deficiency Suppresses 1-Methyl-4-Phenylpyridinium-Induced Oxidative Stress in Astrocytes

Khan, Mohammad Moshahid; Kempuraj, Duraisamy; Zaheer, Smita; Zaheer, Asgar

doi:10.1007/s12031-013-0225-z

Cited by 21 publications

(32 citation statements)

References 52 publications

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“…The reduced release of CCL2 from GMF-KO cells observed in the present study could be due to the inhibition of MAPKs and NF-κB activation as we reported previously (Zaheer et al, 2007). Further, we have also demonstrated that GMF-deficiency in astrocytes upregulates the antioxidant status and limits the extent of lipid peroxidation and production of ROS along with diminished NF-κB-mediated inflammations in MPP + -mediated toxicity (Khan et al, 2014). Our present study shows decreased neurodegeneration with reduced total neurite outgrowth in MPP + treated neuronal cultures obtained from GMF-KO mice brains than from Wt mice brains.…”

Section: Discussionmentioning

confidence: 96%

“…Therefore, we have used GMF-KO cells in only some experiments to study the effect of the mast cell proteases on brain cells. Our previous studies have demonstrated that GMF activates astrocytes through p38 MAPK and NF-κB signaling pathways (Zaheer et al, 2001; Zaheer et al, 2007) and inhibition of these pathways in GMF-KO glial cells also reduced the inflammatory mediator release in vitro (Khan et al, 2014). The reduced release of CCL2 from GMF-KO cells observed in the present study could be due to the inhibition of MAPKs and NF-κB activation as we reported previously (Zaheer et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

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Cross-Talk between Glia, Neurons and Mast Cells in Neuroinflammation Associated with Parkinson’s Disease

Kempuraj

Selvakumar

Zaheer

et al. 2017

J Neuroimmune Pharmacol

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Parkinson’s disease (PD) is a progressive movement disorder characterized by neuroinflammation and dopaminergic neurodegeneration in the brain. 1-methyl-4-phenylpyridinium (MPP+), a metabolite of the parkinsonian neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induces the release of inflammatory mediators from glial cells and neurons. Glia maturation factor (GMF), a brain proinflammatory protein, MPP+, and mast cell-derived inflammatory mediators induce neurodegeneration which eventually leads to PD. However, the precise mechanisms underlying interaction between glial cells, neurons and mast cells in PD still remain elusive. In the present study, mouse bone marrow-derived mast cells (BMMCs) and mouse fetal brain-derived mixed glia/neurons, astrocytes and neurons were incubated with MPP+, GMF and mast cell-derived inflammatory mediators mouse mast cell protease-6 (MMCP-6), MMCP-7 or tryptase/brain-specific serine protease-4 (tryptase/BSSP-4). Inflammatory mediators released from these cells in the culture medium were quantitated by enzyme-linked immunosorbent assay. Neurodegeneration was quantified by measuring total neurite outgrowth following microtubule-associated protein-2 immunocytochemistry. MPP+− induced significant neurodegeneration with reduced total neurite outgrowth. MPP+− induced the release of tryptase/BSSP-4 from the mouse mast cells, and tryptase/BSSP-4 induced chemokine (C-C motif) ligand 2 (CCL2) release from astrocytes and glia/neurons. Overall our results suggest that MPP+, GMF, MMCP-6 or MMCP-7 stimulate glia/neurons, astrocytes or neurons to release CCL2 and matrix metalloproteinase-3. Additionally, CD40L expression is increased in BMMCs after incubation with MPP+ in a co-culture system consisting of BMMCs and glia/neurons. We propose that mast cell interaction with glial cells and neurons during neuroinflammation can be explored as a new therapeutic target for PD.

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Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

Cross-Talk between Glia, Neurons and Mast Cells in Neuroinflammation Associated with Parkinson’s Disease

Kempuraj

Selvakumar

Zaheer

et al. 2017

J Neuroimmune Pharmacol

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“…Interestingly, several novel compounds have been patented for PD treatment based on their iNOS-inhibiting capacities (Zhang et al, 2011;Koppula et al, 2012). Previous studies have demonstrated that PYC has the ability to quench NO radicals and inhibit both iNOS mRNA expression and the iNOS activity (Khan et al, 2014), suggesting its potential application in neurodegenerative disease. In this study, we indeed found that PYC efficiently reduced Rot-induced iNOS/NO.…”

Section: Discussionmentioning

confidence: 99%

Pycnogenol Protects Against Rotenone-Induced Neurotoxicity in PC12 Cells Through Regulating NF-κB-iNOS Signaling Pathway

Gao

Chang

Zhou

et al. 2015

DNA and Cell Biology

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Parkinson's disease (PD) is a common neurodegenerative disorder characterized by dopaminergic neurons degeneration and oxidative damage may underlie this process. However, there are still no efficient drugs to cure the disease. Pycnogenol (PYC) isolated from the procyanidin-rich French maritime pine (Pinus maritime) bark has shown various antioxidant activities in previous studies. In this study, we explored its effect against rotenone (Rot)-induced neurotoxicity and the underlying mechanisms in PC12 cells. Using Rot-induced cell model of PD, we found that PYC treatment significantly increased cell viability and decreased cell apoptosis in Rot-treated PC12 cells in a dose-dependent manner. Furthermore, data showed that PYC markedly reduced inducible nitric oxide synthase (iNOS)-nitric oxide (NO) signaling in Rot-treated PC12 cells. Pretreatment with the iNOS-specific inhibitor significantly attenuated Rot-induced neurotoxicity. Moreover, PYC was found to be capable of reducing Rot-induced NF-κB activation. Blocking NF-κB signaling with its inhibitor mimicked the biological effect of PYC on Rot-induced iNOS and NO expression levels, as well as neurotoxicity in PC12 cells, suggesting that the NF-κB-iNOS signaling pathway was likely to participate in the PYC-mediated protective progress. Our results suggest that PYC protects against Rot-induced neurotoxicity in PC12 cells, and the mechanism may be associated with the downregulation of NF-κB-iNOS signaling pathway.

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“…Dopaminergic neurotoxin 1- methyl -4- phenyl -1,2,3,6-tetrahydro pyridine (MPTP) administration induces PD in animals. 1-methyl-4-phenyl-pyridinium ion (MPP + ), metabolite of MPTP has been shown to induce oxidative stress, mitochondrial damage, glial activation, inflammatory cytokine/chemokine release and dopaminergic neuronal damage [6–8]. …”

Section: Introductionmentioning

confidence: 99%

Mast Cells Release Chemokine CCL2 in Response to Parkinsonian Toxin 1-Methyl-4-Phenyl-Pyridinium (MPP+)

et al. 2015

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Microglial activation and release of inflammatory cytokines and chemokines are crucial events in neuroinflammation. Microglial cells interact and respond to other inflammatory cells such as T cells and mast cells as well as inflammatory mediators secreted from these cells. Recent studies have shown that neuroinflammation causes and accelerates neurodegenerative disease such as Parkinson’s disease (PD) pathogenesis. 1-methyl-4-phenyl-pyridinium ion (MPP+), the active metabolite of neurotoxin 1- methyl -4- phenyl -1,2,3,6-tetrahydro pyridine (MPTP) activates glial cells and mediate neurodegeneration through release of inflammatory mediators. We have shown that glia maturation factor (GMF) activates glia and induces neuroinflammation and neurodegeneration and that MPP+ activates mast cells and release proinflammatory cytokines and chemokines. The chemokine (C-C motif) ligand 2 (CCL2) levels have been shown to be elevated and play a role in PD pathogenesis. In the present study, we analyzed if MPP+ activates mouse and human mast cells to release chemokine CCL2. Mouse bone marrow-derived mast cells (BMMCs) and human umbilical cord blood-derived cultured mast cells (hCBMCs) were incubated with MPP+ (10 μM) for 24 h and CCL2 levels were measured in the supernatant media by ELISA. MPP+-significantly-induced CCL2 release from BMMCs and hCBMCs. Additionally, GMF overexpression in BMMCs obtained from wild-type mice released significantly more CCL2, while BMMCs obtained from GMF-deficient mice showed less CCL2 release. Further, we show that MPP+-induced CCL2 release was greater in BMMCs-astrocyte co-culture conditions. Uncoupling protein 4 (UCP4) which is implicated in neurodegenerative diseases including PD was detected in BMMCs by immunocytochemistry. Our results suggest that mast cells may play role in PD pathogenesis.

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Glia Maturation Factor Deficiency Suppresses 1-Methyl-4-Phenylpyridinium-Induced Oxidative Stress in Astrocytes

Cited by 21 publications

References 52 publications

Cross-Talk between Glia, Neurons and Mast Cells in Neuroinflammation Associated with Parkinson’s Disease

Cross-Talk between Glia, Neurons and Mast Cells in Neuroinflammation Associated with Parkinson’s Disease

Pycnogenol Protects Against Rotenone-Induced Neurotoxicity in PC12 Cells Through Regulating NF-κB-iNOS Signaling Pathway

Mast Cells Release Chemokine CCL2 in Response to Parkinsonian Toxin 1-Methyl-4-Phenyl-Pyridinium (MPP+)

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