The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform

Karam F.a. Soliman - One of the best experts on this subject based on the ideXlab platform.

  • the role of phospholipid methylation in 1 methyl 4 phenyl pyridinium ion MPP induced neurotoxicity in pc12 cells
    Neurotoxicology, 2005
    Co-Authors: Hongtao Chen, Clivel G Charlton, Karam F.a. Soliman
    Abstract:

    Abstract Excessive methylation has been proposed to be involved in the pathogenesis of Parkinson's disease (PD), via mechanisms that involve phospholipid methylation. Meanwhile, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was found to stimulate phospholipid methylation via the oxidized metabolite, 1-methyl-4-phenyl-pyridinium (MPP+), in the rat brain and liver tissues. In the present study, we investigated the effect of MPP+ on phosphatidylethanolamine N-methyltransferases (PENMT) and the potential role of this pathway in MPP+-induced neurotoxicity using PC12 cells. The results obtained indicate that MPP+ stimulated phosphatidylethanolamine (PTE) methylation to phosphatidylcholine (PTC) and correspondingly increased the formation of lysophosphatidylcholine (lyso-PTC). Moreover, the addition of S-adenosylmethionine (SAM) to the cell culture medium increases MPP+-induced cytotoxicity. The incubation of 1 mM MPP+ and various concentrations of SAM (0–4 mM) decreased the viability of PC12 cells from 80% with MPP+ alone to 38% viability with 4 mM SAM for 4 days incubation. The data also revealed that the addition of S-adenosylhomocysteine (SAH), a methylation inhibitor, offered significant protection against MPP+-induced cytotoxicity, indicating that methylation plays a role in MPP+-induced cytotoxicity. Interestingly, lyso-PTC showed similar actions to MPP+ in causing many cytotoxic changes with at least 10 times higher potency. Lyso-PTC induced dopamine release and inhibited dopamine uptake in PC12 cells. Lyso-PTC also caused the inhibition of mitochondrial potential and increased the formation of reactive oxygen species in PC12 cells. These results indicate that phospholipid methylation pathway might be involved in MPP+ neurotoxicity and lyso-PTC might play a role in MPP+-induced neurotoxicity.

Ting Wang - One of the best experts on this subject based on the ideXlab platform.

  • chikusetsu saponin v attenuates MPP induced neurotoxicity in sh sy5y cells via regulation of sirt1 mn sod and grp78 caspase 12 pathways
    International Journal of Molecular Sciences, 2014
    Co-Authors: Ding Yuan, Changcheng Zhang, Lili Deng, Zhiyong Zhou, Jingzhi Wan, Chaoqi Liu, Yaoyan Dun, Yanwen Dai, Ting Wang
    Abstract:

    Studies have shown that saponins from Panax japonicus (SPJ) possess neuroprotective effects. However, whether Chikusetsu saponin V (CsV), the most abundant member of SPJ, can exert neuroprotective effects against 1-methyl-4-phenylpyridinium ion (MPP+)-induced cytotoxicity is not known. In this study, we aimed to investigate the neuroprotective effects of CsV on MPP+-induced cytotoxicity in human neuroblastoma SH-SY5Y cells and explore its possible mechanisms. Our results show that CsV attenuates MPP+-induced cytotoxicity, inhibits ROS accumulation, and increases mitochondrial membrane potential dose-dependently. We also found that levels of Sirt1 protein and Mn-SOD mRNA significantly decreased in MPP+-treated group but were restored with CsV treatment in a dose-dependent manner. Furthermore, GRP78 protein and Caspase-12 mRNA levels were elevated by MPP+ exposure but reversed by CsV treatment. CsV inhibited the MPP+-induced downregulation of Bcl-2 and up-regulation of Bax in a dose-dependent manner and, thus, increased the ratio of Bcl-2/Bax. Overall, these results suggest that Sirt1/Mn-SOD and GRP78/Caspase-12 pathways might be involved in the CsV-mediated neuroprotective effects.

  • Chikusetsu Saponin V Attenuates MPP+-Induced Neurotoxicity in SH-SY5Y Cells via Regulation of Sirt1/Mn-SOD and GRP78/Caspase-12 Pathways
    MDPI AG, 2014
    Co-Authors: Ding Yuan, Changcheng Zhang, Lili Deng, Zhiyong Zhou, Jingzhi Wan, Chaoqi Liu, Yaoyan Dun, Yanwen Dai, Ting Wang
    Abstract:

    Studies have shown that saponins from Panax japonicus (SPJ) possess neuroprotective effects. However, whether Chikusetsu saponin V (CsV), the most abundant member of SPJ, can exert neuroprotective effects against 1-methyl-4-phenylpyridinium ion (MPP+)-induced cytotoxicity is not known. In this study, we aimed to investigate the neuroprotective effects of CsV on MPP+-induced cytotoxicity in human neuroblastoma SH-SY5Y cells and explore its possible mechanisms. Our results show that CsV attenuates MPP+-induced cytotoxicity, inhibits ROS accumulation, and increases mitochondrial membrane potential dose-dependently. We also found that levels of Sirt1 protein and Mn-SOD mRNA significantly decreased in MPP+-treated group but were restored with CsV treatment in a dose-dependent manner. Furthermore, GRP78 protein and Caspase-12 mRNA levels were elevated by MPP+ exposure but reversed by CsV treatment. CsV inhibited the MPP+-induced downregulation of Bcl-2 and up-regulation of Bax in a dose-dependent manner and, thus, increased the ratio of Bcl-2/Bax. Overall, these results suggest that Sirt1/Mn-SOD and GRP78/Caspase-12 pathways might be involved in the CsV-mediated neuroprotective effects

Daniel A Linseman - One of the best experts on this subject based on the ideXlab platform.

  • calpain plays a central role in 1 methyl 4 phenylpyridinium MPP induced neurotoxicity in cerebellar granule neurons
    Neurotoxicity Research, 2011
    Co-Authors: Richard A Harbison, Kristen R Ryan, Heather M Wilkins, Emily K Schroeder, Alexandra F Loucks, Ron J Bouchard, Daniel A Linseman
    Abstract:

    1-Methyl-4-phenylpyridinium (MPP(+))-induced neurotoxicity has previously been attributed to either caspase-dependent apoptosis or caspase-independent cell death. In the current study, we found that MPP(+) induces a unique, non-apoptotic nuclear morphology coupled with a caspase-independent but calpain-dependent mechanism of cell death in primary cultures of rat cerebellar granule neurons (CGNs). Using a terminal deoxynucleotidyl transferase dUTP nick end-labeling (TUNEL) assay in CGNs exposed to MPP(+), we observed that these neurons are essentially devoid of caspase-dependent DNA fragments indicative of apoptosis. Moreover, proteolysis of a well recognized caspase-3 substrate, poly (ADP ribose) polymerase (PARP), was not observed in CGNs exposed to MPP(+). In contrast, calpain-dependent proteolysis of fodrin and pro-caspases-9 and -3 occurred in this model coupled with inhibition of caspase-3/-7 activities. Notably, several key members of the Bcl-2 protein family appear to be prominent calpain targets in MPP(+)-treated CGNs. Bid and Bax were proteolyzed to truncated forms thought to have greater pro-death activity at mitochondria. Moreover, the pro-survival Bcl-2 protein was degraded to a form predicted to be inactive at mitochondria. Cyclin E was also cleaved by calpain to an active low MW fragment capable of facilitating cell cycle re-entry. Finally, MPP(+)-induced neurotoxicity in CGNs was significantly attenuated by a cocktail of calpain and caspase inhibitors in combination with the antioxidant glutathione. Collectively, these results demonstrate that caspases do not play a central role in CGN toxicity induced by exposure to MPP(+), whereas calpain cleavage of key protein targets, coupled with oxidative stress, plays a critical role in MPP(+)-induced neurotoxicity. Our findings underscore the complexity of MPP(+)-induced neurotoxicity and suggest that calpain may play a fundamental role in causing neuronal death downstream of mitochondrial oxidative stress and dysfunction.

Yasuyuki Nomura - One of the best experts on this subject based on the ideXlab platform.

  • 1 methyl 4 phenyl pyridinium ion MPP causes dna fragmentation and increases the bcl 2 expression in human neuroblastoma sh sy5y cells through different mechanisms
    Brain Research, 1995
    Co-Authors: Yasuhiro Itano, Yasuyuki Nomura
    Abstract:

    Abstract Apoptosis has been shown to be induced by some pathological stimuli. MPP+ is a neurotoxin and an inducer of parkinsonism. When SH-SY5Y cells, human neuroblastoma cell line, were treated with MPP+, cell death estimated by lactate dehydrogenase (LDH) leakage assay occurred. The cell death was associated with the DNA fragmentation into nucleosomal fragments at 180 bp, suggesting that MPP+-induced cell death of SH-SY5Y cells occurs through apoptosis. Although SH-SY5Y cells natively express Bcl-2 protein, which inhibits apoptosis, the level of Bcl-2 protein in SH-SY5Y cells increased with increases in the treatment periods of MPP+. MPP+ inhibits the mitochondrial respiratory chain. The other inhibitors of the mitochondrial respiratory chain, antimycin A and oligomycin, also caused cell death associated with DNA fragmentation, but did not increase the Bcl-2 protein level, suggesting that an MPP+-induced apoptosis may be due to the inhibition of the mitochondrial respiratory chain but the MPP+-induced increase in the Bcl-2 protein level is not due to it. A protein kinase inhibitor, staurosporine, inhibited the MPP+-induced increase in the Bcl-2 protein level, but not the MPP+-induced cell death. These results also suggest that the mechanism by which MPP+ increases the Bcl-2 protein level is different from that of MPP+-induced cell death.

Yasumitsu Yamanaka - One of the best experts on this subject based on the ideXlab platform.

  • release of dopamine by perfusion with 1 methyl 4 phenylpyridinium ion MPP into the striatum is associated with hydroxyl free radical generation
    Brain Research, 2001
    Co-Authors: Toshio Obata, Hiroyasu Kinemuchi, Yasumitsu Yamanaka, Lars Oreland
    Abstract:

    Abstract In Parkinson’s disease (PD), the dopamine (DA) neuronal cell death in the nigrostriatal system has been proposed to be mediated by reactive oxygen radicals such as hydroxyl radicals (·OH). This ·OH production may cause lipid peroxidation of cell membranes leading to neuronal cell death. This paper report that the DA-selective neurotoxin, 1-methyl-4-phenylpyridinium ion (MPP+), (1 nmol/μl per min for 1 h) infusion into the striatum of rats induces elevation of extracellular DA and ·OH formation. These elevations seem to induce lipid peroxidation of striatum membranes, as detected by increases in non-enzymatic formation of 2,3-dihydroxybenzoic acid (DHBA) levels. To test the involvement of DA release in the ·OH generation and lipid peroxidation, the rats were pretreated with reserpine (5 mg/kg, i.v., 24 h before MPP+ or without MPP+) to deplete presynaptic DA. Reserpine treatment alone did not change the levels of DA or 2,3-DHBA, while the combined treatment with both MPP+ and reserpine clearly decreased 2,3-DHBA, as well as DA levels, compared to those in the group treated with MPP+ alone. After injection into reserpinized rats, DA at various doses (2, 5 and 10 μM) small increased 2,3-DHBA levels dose-dependently, as compared to the MPP+ alone-treated group. These results clearly indicate that MPP+ perfusion into the striatum increases extracellular DA levels and this increase may concomitantly induce the formation of reactive free oxygen radicals, such as ·OH free radicals. These events may contribute, at least in part, to the nigrostriatal neurons cell death after MPP+.

  • allopurinol suppresses para nonylphenol and 1 methyl 4 phenylpyridinium ion MPP induced hydroxyl radical generation in rat striatum
    Neuroscience Letters, 2001
    Co-Authors: Toshio Obata, Shunichiro Kubota, Yasumitsu Yamanaka
    Abstract:

    Abstract We recently demonstrated that para-nonylphenol, an environmental estrogen-like chemical, enhances hydroxyl radical ( OH) generation in the rat striatum. In the present study we have examined whether para-nonylphenol enhanced 1-methyl-4-phenylpyridinium ion (MPP + )-induced OH generation in the rat striatum using a microdialysis technique. Para-nonylphenol significantly enhanced MPP + -induced OH generation. Further, we studied the effect of allopurinol, a xanthine oxidase inhibitor, on para-nonylphenol and MPP + -induced OH generation. Allopurinol significantly suppressed para-nonylphenol and MPP + -induced OH generation. The results indicate that para-nonylphenol enhanced OH generation based on superoxide anion production, and allopurinol may have preventive effect on para-nonylphenol and MPP + -induced OH generation.