Alpha-tocopherol-mediated long-lasting protection against oxidative damage involves an attenuation of calcium entry through TRP-like channels in cultured hippocampal neurons.
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.
Crouzin
Nadine
N
Oxidative Stress and Neuroprotection, IBMM UMR-5247 CNRS, University Montpellier II, Place E. Bataillon, 34095 Montpellier cedex 05, France.
de Jesus Ferreira
Marie-Céleste
MC
Cohen-Solal
Catherine
C
Aimar
Rose-France
RF
Vignes
Michel
M
Guiramand
Janique
J
D000818:Animals; D001692:Biological Transport; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D004249:DNA Damage / Q000187:drug effects*; D006624:Hippocampus / Q000166:cytology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D050052:TRPC Cation Channels / Q000187:drug effects / Q000502:physiology*; D024502:alpha-Tocopherol / Q000494:pharmacology*
D015220:Calcium Channels; D050052:TRPC Cation Channels; D024502:alpha-Tocopherol; D002118:Calcium