Max Mousseron Institute of Biomolecules, Montpellier, France.
Mol Nutr Food Res. 2010 Apr;54(4):496-505. doi: 10.1002/mnfr.200900188.
Pretreatment of cultured hippocampal neurons with a low concentration of alpha-tocopherol (alpha-TP), the major component of vitamin E, results in a long-lasting protection against oxidative damages, via genomic effects. This neuroprotection is associated with the attenuation of a calcium influx triggered by oxidative agents such as Fe(2+) ions. This Ca(2+) influx is supported by a TRP-like channel, also partly involved in capacitive calcium entry within neurons. Here, we evidence the contribution of TRPV1 channels in this mechanism. TRPV1 channels are activated by various agents including capsaicin, the pungent component of hot chili peppers and blocked by capsazepine (CPZ) or 5'-iodo-resiniferatoxin. Both TRPV1 inhibitors strongly reduced Fe(2+) ion-mediated toxicity and Ca(2+) influx, in the same way as to alpha-TP pretreatment. Moreover, CPZ also decreased capacitive calcium entry in hippocampal neurons. Finally, both CPZ and 5'-iodo-resiniferatoxin reduced spontaneous excitatory synaptic transmission; this depression of synaptic transmission being largely occluded in alpha-TP-pretreated neurons. In conclusion, in our experimental model, TRPV1 channels are involved in the Fe(2+) ion-induced neuronal death and a negative modulation of this channel activity by alpha-TP pretreatment may account, at least in part, for the long-lasting neuroprotection against oxidative stress.
用低浓度的 α-生育酚（α-TP）预处理培养的海马神经元，通过基因组效应，可产生长期的抗氧化损伤保护作用。这种神经保护作用与氧化应激剂（如 Fe(2+)离子）触发的钙内流的衰减有关。这种 Ca(2+)内流由一种类似于 TRP 的通道支持，该通道也部分参与神经元内的电容性钙内流。在这里，我们证明 TRPV1 通道在这种机制中的作用。TRPV1 通道可被各种物质激活，包括辣椒素，这是热辣椒的辣味成分，并用辣椒素（CPZ）或 5'-碘-Resiniferatoxin（5'-I-RTX）阻断。两种 TRPV1 抑制剂均强烈降低 Fe(2+)离子介导的毒性和 Ca(2+)内流，与 α-TP 预处理的方式相同。此外，CPZ 还减少了海马神经元中的电容性钙内流。最后，CPZ 和 5'-碘-Resiniferatoxin 均降低了自发性兴奋性突触传递；这种突触传递的抑制在经过 α-TP 预处理的神经元中被大量阻断。总之，在我们的实验模型中，TRPV1 通道参与 Fe(2+)离子诱导的神经元死亡，而 α-TP 预处理对该通道活性的负调控可能至少部分解释了对氧化应激的长期神经保护作用。
