University of Hertfordshire

Documents

View graph of relations
Original languageEnglish
Pages (from-to)844-854
Number of pages11
JournalNeurochemical research
Volume41
Issue4
Early online date11 Nov 2015
DOIs
Publication statusPublished - 1 Apr 2016

Abstract

Etidronate 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.

Notes

This 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.

ID: 9538179