, Volume 1, Issue 2, pp 127-132

Effects of homocysteine and homocysteinic acid on cerebellar granule cells

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Abstract

Homocysteine (HC) and homocysteinic acid (HCA) were capable of elevating the intracellular level of calcium ions and active oxygen forms (AOF) in rat cerebellum neurons similarly to NMDA. The NMDAreceptor antagonist, MK-801, prevented the rise of both indexes induced by HC or HCA, whereas α-methylcarboxyphenylglycine (an antagonist of metabotropic glutamate receptors of group I) did not interfere with the effect HC or HCA. Chelation of intracellular calcium by 1,2-bis(2-aminophenoxy)ethen-N,N,N′,N′-tetraacetic acid (the BAPTA intracellular calcium buffer) decreased AOF generation during neuron activation by HC or HCA to the control level. NMDA, HC, and HCA induced phosphatidylserine externalization in neurons, which was one of the early stages of apoptosis induced by AOF. Induction of apoptosis by HCA was partially prevented by BAPTA, N-acetylcysteine or cyclosporine A. These facts could be the basis of the neurotoxic effects of HC and its derivatives.

Original Russian Text © A.V. Makhro, E.R. Bulygina, A.A. Boldyrev, 2007, published in Neirokhimiya, 2006, vol. 23, No. 3, pp. 179–184.