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KMID : 1034820080040020157
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Molecular & Cellular Toxicology
2008 Volume.4 No. 2 p.157 ~ p.163
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Protective Effect of Citrate against -induced Neurotoxicity in PC12 Cells
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Yang Hyun-Duk
Son Il-Hong
Lee Sung-Soo
Park Yong-Hoon
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Abstract
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Formation of -amyloid fibrils has been identified as one of the major characteristics of Alzheimer’s disease (AD). Inhibition of fibril formation in the CNS would be attractive therapeutic targets for the treatment of AD. Several small compounds that inhibit amyloid formation or amyloid neurotoxicity in vitro have been known. Citrate has surfactant function effect because of its molecular structure having high anionic charge density, in addition to the well-known antibacterial and antioxidant properties. Therefore, we hypothesized that citrate might have the inhibitory effect against fibril formation in vitro and have the protective effect against -induced neurotoxicity in PC12 cells. We examined the effect of citrate against the formation of fibrils by measuring the intensity of fluorescence in thioflavin-T (Th-T) assay of between groups treated with citrate and the control with alone. The neuroprotective effect of citrate against -induced toxicity in PC12 cells was investigated using the WST-1 assay. Fluorescence spectroscopy showed that citrate inhibited dose-dependently the formation of fibrils from -amyloid peptides. The inhibition percentages of fibril formation by citrate (1, 2.5, and 5 mM) were 31%, 60%, and 68% at 7 days, respectively in thioflavin-T (Th-T) assay. WST-1 assay revealed that the toxic effect of was reduced, in a dose-dependent manner to citrate. The percentages of neuroprotection by citrate (1, 2.5, and 5 mM) against toxicity were 19%, 31 %, and 34%, respectively. We report that citrate inhibits the formation of fibrils in vitro and has neuroprotective effect against -induced toxicity in PC12 cells. Neuroprotective effects of citrate against might be, to some extent, attributable to its inhibition of fibril formation. Although the mechanism of anti-amyloidogenic activity is not clear, the possible mechanism is that citrate might have two effects, salting-in and surfactant effects. These results suggest that citrate could be of potential therapeutic value in Alzheimer’s disease.
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KEYWORD
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Citrate, Alzheimer’s disease-amyloid, PC12 cell, Fibril
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