Jin H, Chen W Q, Tang X W, Chiang L Y, Yang C Y, Schloss J V, Wu J Y
Department of Molecular Biosciences, University of Kansas, Lawrence, Kansas 66045, USA.
J Neurosci Res. 2000 Nov 15;62(4):600-7. doi: 10.1002/1097-4547(20001115)62:4<600::AID-JNR15>3.0.CO;2-F.
Derivatives of C(60) have been shown to be effective free radical scavengers. Hence, many of the biological functions of fullerene are believed to be due to their antioxidant properties. Here we present evidence to show that fullerenols, that are caged fullerene oxides, exert their neuroprotective functions by blocking glutamate receptors and lowering the intracellular calcium, Ca(2+). In neuronal cultures, fullerenols reduce glutamate-induced neurotoxicity by about 80% at 50microM. No significant effect was observed on H(2)O(2)/Fe(2+)-induced neurotoxicity under the same conditions. Fullerenols were found to inhibit glutamate receptor binding in a dose-dependent manner inhibiting 50% of glutamate binding at 50 microM. Furthermore, AMPA receptors were found to be more sensitive to fullerenols than NMDA and KA receptors. On the other hand, GABA(A) receptors and taurine receptors were not significantly affected by fullerenols at the same concentrations used, suggesting that fullerenols inhibit primarily the glutamate receptors. In addition, fullerenols were also found to lower glutamate (Glu) receptor-induced elevation of Ca(2+), suggesting that the underlying mechanism of neuronal protective function of fullerenols is likely due to its ability to block the glutamate receptors and to reduce the level of Ca(2+).
C(60) 的衍生物已被证明是有效的自由基清除剂。因此，富勒烯的许多生物学功能被认为归因于其抗氧化特性。在此，我们提供证据表明，作为笼状富勒烯氧化物的富勒醇，通过阻断谷氨酸受体并降低细胞内钙浓度 Ca(2+) 来发挥其神经保护功能。在神经元培养物中，50μM 的富勒醇可将谷氨酸诱导的神经毒性降低约 80%。在相同条件下，未观察到对 H(2)O(2)/Fe(2+) 诱导的神经毒性有显著影响。发现富勒醇以剂量依赖性方式抑制谷氨酸受体结合，在 50μM 时抑制 50% 的谷氨酸结合。此外，发现 AMPA 受体比 NMDA 和 KA 受体对富勒醇更敏感。另一方面，在相同浓度下，GABA(A) 受体和牛磺酸受体未受到富勒醇的显著影响，这表明富勒醇主要抑制谷氨酸受体。此外，还发现富勒醇可降低谷氨酸 (Glu) 受体诱导的 Ca(2+) 升高，这表明富勒醇神经保护功能的潜在机制可能是由于其阻断谷氨酸受体并降低 Ca(2+) 水平的能力。
