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dc.contributor.authorLi, Wen
dc.contributor.authorCheong, Yuen-Ki
dc.contributor.authorWang, Hui
dc.contributor.authorRen, Guogang
dc.contributor.authorYang, Zhuo
dc.date.accessioned2017-08-17T15:55:31Z
dc.date.available2017-08-17T15:55:31Z
dc.date.issued2016-04-01
dc.identifier.citationLi , W , Cheong , Y-K , Wang , H , Ren , G & Yang , Z 2016 , ' Neuroprotective Effects of Etidronate and 2,3,3-Trisphosphonate Against Glutamate-Induced Toxicity in PC12 Cells ' , Neurochemical research , vol. 41 , no. 4 , pp. 844-854 . https://doi.org/10.1007/s11064-015-1761-4
dc.identifier.issn0364-3190
dc.identifier.otherPURE: 9538179
dc.identifier.otherPURE UUID: 2b0892be-0346-4fab-820b-397251f9e718
dc.identifier.otherScopus: 84946771662
dc.identifier.otherPubMed: 26559687
dc.identifier.otherScopus: 84946771662
dc.identifier.urihttp://hdl.handle.net/2299/19234
dc.descriptionThis document is the Accepted Manuscript version of the following article: Wen Li, Yuen-Ki Cheong, Hui Wang, Guogang Ren and Zhuo Yang, ‘Neuroprotective Effects of Etidronate and 2,3,3-Trisphosphonate Against Glutamate-Induced Toxicity in PC12 Cells’, Neurochemical Research, Vol. 41 (4): 844-854, April 2016. The final publication is available at Springer via https://doi.org/10.1007/s11064-015-1761-4.
dc.description.abstractEtidronate is one of the best known bisphosphonates (BP) derivatives. It is often used as a reference drug in research related to hypercalcaemia and other common bone diseases. 2,3,3-trisphosphonate (TrisPP) is brand new analogue of BP, that also contains a ‘germinal bisphosphonate’ unit with an additional phosphoryl group attached in proximity to the BP unit. It is known that BPs bind to calcium by chemisorptions to form Ca-BP complexes through (O)P–C–P(O) moiety and hydrogen coordinations, and so they suppress calcium flow by interfering with Ca2+ channel operations. The mechanistic actions of BP, involving interactions and regulations of Ca2+, are somewhat similar to the pathogenesis of well-known neurodegenerative disorders, such as Alzheimer’s disease, Parkinson’s disease and Huntington’s disease. To investigate if neuroprotective effects are exhibited by the compounds of interests, we used a rat adrenal pheochromocytoma cell line (PC12) as our in vitro model to observe any occurrence of neuron inter-reflection. We pre-treated these PC12 cells with etidronate and TrisPP before challenging the cells with a high concentration of the neurotoxin, glutamate. Our data showed that pre-treatment with 100 μM etidronate partially ameliorated the glutamate-induced decrease in cell viability (47 %), whereas pre-treating cells with 10–100 μM TrisPP showed remarkable cell protection (78–86 %). Moreover, pre-treatments of the cells with etidronate or TrisPP attenuated cell apoptosis, reactive oxygen species generation, Ca2+ overloading and caspase-3 protein expression, which were associated with a remarkable increase in superoxide dismutase activity in our glutamate-injured PC12 cells. Therefore, this study supports the notion that etidronate and TrisPP may be promising neuroprotective agents.en
dc.format.extent11
dc.language.isoeng
dc.relation.ispartofNeurochemical research
dc.rightsEmbargoed
dc.subject2,3,3-Trisphosphonate
dc.subjectEtidronate
dc.subjectGlutamate
dc.subjectNeuroprotection
dc.subjectPC12 cells
dc.subjectCellular and Molecular Neuroscience
dc.subjectBiochemistry
dc.titleNeuroprotective Effects of Etidronate and 2,3,3-Trisphosphonate Against Glutamate-Induced Toxicity in PC12 Cellsen
dc.contributor.institutionSchool of Engineering and Technology
dc.contributor.institutionCentre for Engineering Research
dc.contributor.institutionMaterials and Structures
dc.description.statusPeer reviewed
dc.date.embargoedUntil2016-11-11
dc.relation.schoolSchool of Engineering and Technology
dc.description.versiontypeFinal Accepted Version
dcterms.dateAccepted2016-04-01
rioxxterms.versionAM
rioxxterms.versionofrecordhttps://doi.org/10.1007/s11064-015-1761-4
rioxxterms.licenseref.startdate2016-11-11
rioxxterms.typeJournal Article/Review
herts.preservation.rarelyaccessedtrue
herts.date.embargo2016-11-11
herts.rights.accesstypeEmbargoed


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