Scorziello A, Florio T, Bajetto A, Thellung S, Schettini G
Institute of Pharmacology, School of Medicine, University of Genova, Italy.
J Neurosci Res. 1997 Sep 1;49(5):600-7. doi: 10.1002/(SICI)1097-4547(19970901)49:5<600::AID-JNR10>3.0.CO;2-Z.
HIV-1 infection frequently induces neuronal death responsible for the development of neurological deficits associated with AIDS. Several reports suggest that gp120, the HIV-1 envelope glycoprotein, is the main candidate as mediator of the HIV-1-dependent neurotoxicity. Here we report the effect of gp120 on the survival of cortical neurons in vitro and the possible mechanisms whereby it occurs. Mature cortical neurons, cultured on a feeder layer of astrocytes, were treated with gp120 in a defined culture medium in absence of serum. The treatment with gp120 induced time-dependent neuronal damage displaying apoptotic features, as revealed by in situ labelling of DNA fragmentation. TGF-beta1, a cytokine that has been previously shown to exert neuroprotective effects, prevented the cell death induced by exposure of cortical neurons to gp120. The prolonged treatment with gp120 also increased neuronal [Ca2+]i, while the coincubation with TGF-beta1 completely prevented the impairment of neuronal Ca2+ homeostasis. These data, taken together, demonstrate that gp120 induces apoptosis in cortical neurons, an effect that can be related to the impairment of Ca2+ homeostasis, and that TGF-beta1 pretreatment reverts both the neuronal death and the alterations in neuronal [Ca2+]i.
HIV-1感染常常导致神经元死亡，这是与艾滋病相关的神经功能缺损发展的原因。几份报告表明，HIV-1包膜糖蛋白gp120是HIV-1依赖性神经毒性介导因子的主要候选者。在此，我们报告gp120对体外培养的皮质神经元存活的影响以及其发生的可能机制。在无血清的特定培养基中，将在星形胶质细胞饲养层上培养的成熟皮质神经元用gp120处理。如DNA片段原位标记所示，gp120处理诱导了具有凋亡特征的时间依赖性神经元损伤。TGF-β1是一种先前已显示具有神经保护作用的细胞因子，它可预防皮质神经元暴露于gp120所诱导的细胞死亡。用gp120进行长时间处理也会增加神经元的细胞内钙离子浓度（[Ca2+]i），而与TGF-β1共同孵育则完全防止了神经元钙离子稳态的受损。综上所述，这些数据表明gp120诱导皮质神经元凋亡，这种效应可能与钙离子稳态受损有关，并且TGF-β1预处理可逆转神经元死亡以及神经元[Ca2+]i的改变。
