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Alpha-tocopherol-mediated long-lasting protection against oxidative damage involves an attenuation of calcium entry through TRP-like channels in cultured hippocampal neurons.

Abstract : We have reported that a transient treatment of hippocampal neurons with alpha-tocopherol induced a long-lasting protection against oxidative damage mediated by Fe(2+) ions. This protection required protein synthesis. Here, we have studied whether this "hyposensitivity" to oxidative stress could be linked to an altered Ca(2+) homeostasis. Fe(2+) ions triggered a Ca(2+) entry which was required for Fe(2+) ion-induced toxicity. This influx was sensitive to blockers of TRP-like nonspecific Ca(2+) channels, including Ruthenium Red, La(3+), and Gd(3+) ions which also prevented the Fe(2+) ion-induced toxicity and oxidative stress as revealed by protein carbonylation status. The pretreatment with alpha-tocopherol resulted in a reduction of the Ca(2+) increase induced by Fe(2+) ions and masked the blocking effect of La(3+) ions. Moreover, such a pretreatment reduced the capacitive Ca(2+) entries (CCE) observed after metabotropic glutamate receptor stimulation, which are known to involve TRP-like channels. By contrast, in a model of "hypersensitivity" to oxidative stress obtained by chronic stimulation of glucocorticoid receptors, we observed an exacerbation of the various effects of Fe(2+) ions, i.e., cellular toxicity and Ca(2+) increase, and the glutamate-stimulated CCE. Therefore, we conclude that the long-lasting neuroprotection induced by alpha-tocopherol pretreatment likely results from an attenuation of Ca(2+) entries via TRP-like channels.
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https://hal.archives-ouvertes.fr/hal-00397592
Contributor : Janique Guiramand <>
Submitted on : Monday, June 22, 2009 - 3:35:32 PM
Last modification on : Tuesday, May 28, 2019 - 5:04:05 PM

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Nadine Crouzin, Marie-Céleste de Jesus Ferreira, Catherine Cohen-Solal, Rose-France Aimar, Michel Vignes, et al.. Alpha-tocopherol-mediated long-lasting protection against oxidative damage involves an attenuation of calcium entry through TRP-like channels in cultured hippocampal neurons.. Free Radical Biology and Medicine, Elsevier, 2007, 42 (9), pp.1326-37. ⟨10.1016/j.freeradbiomed.2007.01.032⟩. ⟨hal-00397592⟩

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