Vesce S, Bezzi P, Rossi D, Meldolesi J, Volterra A
Institute of Pharmacological Sciences, University of Milan, Italy.
FEBS Lett. 1997 Jul 7;411(1):107-9. doi: 10.1016/s0014-5793(97)00674-1.
The mechanisms of HIV-1 neurotoxicity remain still undefined although the induction of signalling events and a modest inhibition of glutamate uptake induced by the envelope glycoprotein, gp120, have called attention to astrocytes. Here we demonstrate that the levels at which the viral glycoprotein affects glutamate homeostasis of astrocyte cultures are at least two: not only the inhibition of uptake, due to an effect at site(s) away from the transporters of the amino acid but also a slow stimulation of release. The combination of these two events accounts for a considerable steady increase of the extracellular concentration of the excitatory amino acid which could play an important role in the neurotoxicity often observed in AIDS patients.
尽管包膜糖蛋白gp120诱导的信号事件以及对谷氨酸摄取的适度抑制已引起人们对星形胶质细胞的关注，但HIV-1神经毒性的机制仍未明确。在此，我们证明病毒糖蛋白影响星形胶质细胞培养物中谷氨酸稳态的水平至少有两个：不仅是由于在远离氨基酸转运体的位点产生的作用而导致摄取受到抑制，而且还缓慢刺激了释放。这两个事件的结合导致兴奋性氨基酸细胞外浓度持续显著升高，这可能在艾滋病患者中经常观察到的神经毒性中起重要作用。
