Daidzin protects PC12 cells from serum deprivation-induced apoptosis

This article examines the effect of daidzin on PC12 cell apoptosis induced by serum-free medium. PC12 cell survival was measured by MTT assay. The DNA content and percentage of apoptosis were monitored by flow cytometry and DNA fragmentation was analyzed by agarose gel electrophoresis. The results showed that serum-free (12 h) medium induced apoptosis in PC12 cells. When the cells had been treated with daidzin (0.1, 1 μM) for 12 h, the percentage of PC12 cell apoptosis was significantly decreased to 12.21 and 4.24% from 91.94% in the group with serum deprivation, and DNA fragmentation was prevented. Daidzin (0.01-10 μM) attenuated the cytotoxic effect of sodium cyanide (20 mM), glutamate (0.5 mM) and sodium nitroprusside (0.5 mM) in a manner dependent on concentration. The results suggested that daidzin prevented PC12 cell from serum free-induced apoptosis.     

Inhibition of serum deprivation-induced PC12 cell apoptosis by tanshinone II A.

AIM: To study the effect of tanshinone II A (Tan II A) on PC12 cell apoptosis induced by serum deprivation. METHODS: PC12 cell survival was measured by MTT assay. The DNA content and percentage of apoptosis were monitored by flow cytometry and DNA fragmentation was analyzed by agarose gel electrophoresis. RESULTS: Serum-free (12 h) medium induced apoptosis in PC12 cells. When the cells had been treated with Tan II A (0.1 and 1 micromol . L-1) for 12 h, the percentage of PC12 cell apoptosis was greatly decreased to 25.71 % and 4.89 % from 96.07 % in serum deprivation alone group, and DNA fragmentation was prevented. Tan II A (0.01 - 10 micromol . L-1) attenuated the cytotoxic effect of sodium cyanide (20 mmol . L-1), glutamate (0.5 mmol . L-1), and sodium nitroprusside (0.5 mmol . L-1). CONCLUSION: Tan II A prevented PC12 cells from apoptosis induced by serum-free medium.     

Anti-apoptotic effect of memantine against staurosporine- and low-potassium-induced cell death in cerebellar granule cells: a development-dependent effect

Memantine, a NMDA receptor antagonist used in several experimental models of neuronal cell injury, is a neuroprotective agent that can attenuate neuronal apoptosis connected with over-stimulation of NMDA receptors. In the present study, we evaluated the impact of memantine on apoptosis in primary cerebellar granule cell (CGC) cultures at 7 and 12 day in vitro (DIV). Cell death was induced by staurosporine (St, 0.5 μM) or by decreasing the level of potassium in the culture medium (LP, 5 mM KCl). Both treatments induced cell death in CGC with higher cell-damaging effects at 12 DIV and 7 DIV neurons for St and LP, respectively._Memantine (0.1–2 μM) partially attenuated St-induced apoptosis only in 7 DIV CGC as assessed by DNA fragmentation and LDH release, but not caspase-3 activity. During LP-induced apoptosis, memantine decreased LDH release and DNA fragmentation, but not affected caspase-3 activity in 7 and 12 DIV CGC. Interestingly, we found no beneficial effects of other NMDA antagonists, including a competitive antagonist such as AP-5 (100 μM) and an uncompetitive antagonist such as MK-801, (1 μM). In conclusion, our data suggest that the anti-apoptotic effects of memantine in CGC are developmentally regulated and its neuroprotective action occurs through an NMDAR-independent mechanism.     

丁基苯酞抑制低氧低糖诱导的大鼠皮质神经细胞凋亡

目的：以原代培养的大鼠胎鼠皮质神经元低氧低糖再复氧为模型,研究丁基苯酞对神经细胞凋亡的抑制作用。方法：用流式细胞术检测DNA含量及凋亡细胞百分率,透射电镜观察细胞形态学变化,DNA琼脂糖凝胶电泳和原位末段标记(TUNEL)检测DNA断裂。 结果：丁基苯酞能减轻细胞核形态的改变,减少DNA断裂和阳性细胞数,使低氧低糖诱导的神经细胞凋亡百分率明显下降,凋亡峰显著降低。 结论：丁基苯酞对低氧低糖诱导的大鼠皮质神经细胞凋亡有抑制作用。     

Protective effect of lignophenol derivative from beech (Fagus crenata Blume) on copper- and zinc-mediated cell death in PC12 cells

Lignophenol, prepared using a phase-separation system, is a derivative of lignin, which is one of the components in the plant cell wall, and possesses high phenolic function, high stability and antioxidant properties. However, little is known about the beneficial effect of lignophenol. In this study, we investigated the protective effect of lignophenol from the beech tree (Fagus crenata Blume) on copper- and zinc-mediated apoptosis in PC12 cells by using DNA fragmentation and TUNEL assays. In DNA fragmentation assays, the DNA ladder patterns in the PC12 cells treated with 200 microM Cu and 200 microM Zn were enhanced, whereas the DNA ladder pattern was hardly observed in these cells treated with 20 mM lignophenol. In the TUNEL assay, TUNEL signals increased significantly in the untreated PC12 cells exposed to 200 microM Cu compared with the control. In contrast, the degree of apoptosis in the 20 mM lignophenol-treated cells was significantly lower than in the untreated cells, indicating that lignophenol inhibited Cu-induced apoptotic cell death in PC 12 cells. In the 200 microM Zn-exposed group, the degree of apoptosis in the 20 mM lignophenol-treated cells was also low compared with the untreated cells. In conclusion, these results suggest that lignophenol plays a role in protecting against Cu- and Zn-mediated PC12 apoptotic cell death.     

Scutellarin protects PC12 cells from oxidative stress-induced apoptosis

The present study investigated the effects of scutellarin on oxidative stress-induced cell apoptosis in PC12 cells. Exposure of cells to hydrogen peroxide (H₂O₂) triggered a typical apoptosis, as evidenced by DNA fragmentation, DNA loss and externalization of phosphatidylserine (PS). This treatment also caused significant elevation of oxidative stress characterized by intracellular accumulations of reactive oxygen species (ROS) and malondialdehyde (MDA), a product of lipid peroxidation. Preincubation of cells with scutellarin significantly inhibited the fragmentation and loss of DNA, the externalization of PS, and decreased the percentage of cell apoptosis. Also, intracellular accumulations of ROS and MDA resulting from H₂O₂ exposure were significantly reduced by scutellarin. These findings suggest that scutellarin exerts significant protection against oxidative stress-induced apoptosis, which might be beneficial for the prevention and treatment of oxidative stress-mediated disorders.     

The role of dopamine transporter in selective toxicity of manganese and rotenone

The dopamine transporter has been shown to be the most relevant target site for the specificity of 1-methyl-4-phenylpyridinium ion (MPP+), a neurotoxin for dopaminergic neurons. In contrast, the mechanisms underlying the selective toxicity of manganese and rotenone, potentially toxic agents implicated in dopaminergic neuronal cell death, remain unknown. The aim of this study was to determine the cellular mechanisms of manganese or rotenone uptake in dopaminergic cells via the dopamine transporter. PC12 cells overexpressing the dopamine transporter, which were exposed to 10microM MPP+, showed extensive DNA fragmentation, a biochemical hallmark of apoptosis, whereas wild-type PC12 cells or vector-transfected PC12 cells, which were exposed to 5mM MPP+, did not show DNA fragmentation. In contrast, manganese and rotenone induced DNA fragmentation at slightly lower concentrations in PC12 cells overexpressing the dopamine transporter compared to control cells. Dopamine transporter inhibitors, such as mazindol, nomifensine, or GBR12909, inhibited MPP+-induced DNA fragmentation but did not affect manganese- and rotenone-induced DNA fragmentation in PC12 cells overexpressing the dopamine transporter. Finally, manganese accumulated to similar levels in PC12 cells overexpressing the dopamine transporter and control PC12 cells following incubation with manganese chloride. These results suggested that the dopamine transporter dose not confer cytotoxicity to manganese and rotenone.     

Possible role of interleukin-6 in PC12 cell death induced by MPP+ and tetrahydroisoquinoline

Interleukin (IL)-6 has been shown to protect neuronal cells from cell death induced by various stimulants. Although neuronal cells including PC12 cells were shown to produce IL-6, little is known about the effects of dopaminergic neurotoxins, 1,2,3,4-tetrahydroisoquinoline (TIQ) and 1-methyl-4-phenylpyridinium ion (MPP(+)), on IL-6 expression in PC12 cells. In the present study, we investigated the role of IL-6 in the TIQ- and MPP(+)-induced cell death in PC12 cells. Treatment with 3.2 mM TIQ for 24 h caused a delayed cell death (lactate dehydrogenase (LDH) leakage and nuclear DNA fragmentation) markedly 72 h after the addition. Addition of 0.4 mM MPP(+) caused LDH leakage and nuclear DNA fragmentation 24 h after the addition. The cell death induced by MPP(+) was inhibited by an inhibitor of caspases, z-Val-Ala-Asp(OMe)-fluoromethylketone. The cell death induced by TIQ or MPP(+) was inhibited by nerve growth factor and 10% serum and significantly enhanced by the treatment with anti-IL-6 antibody. Both neurotoxins decreased the IL-6 mRNA level in PC12 cells without changing the other tested mRNA levels (IL-1 alpha, beta-actin, etc.). These findings suggest that dopaminergic neurotoxins cause cell death in PC12 cells at least partially by changing IL-6 expression.     

氧化型低密度脂蛋白对PC12细胞的毒性作用

目的 :探讨氧化型低密度脂蛋白 (oxLDL)对PC1 2细胞的毒性作用。方法 :通过HE染色、透射电镜、MTT实验、LDH释放实验、TUNEL实验及Caspase 3测定来观察oxLDL对PC1 2细胞形态、存活率、细胞膜通透性、细胞核及Caspase 3活性的影响。结果 :透射电镜及光镜下oxLDL作用的PC1 2细胞以坏死为主并伴少量凋亡细胞。细胞存活率随着ox LDL浓度及作用时间增加而下降 ;LDH释放率、TUNEL阳性细胞数及Caspase 3活性随着浓度增高而增高 ;LDL对上述各项指标无影响。结论 :oxLDL通过Caspase 3途径致PC1 2细胞的毒性作用主要以坏死细胞为主并伴少量凋亡细胞 ,并呈量效与时效关系 ;而LDL无细胞毒性作用     

Nonylphenol diethoxylate inhibits apoptosis induced in PC12 cells

Nonylphenol and short‐chain nonylphenol ethoxylates such as NP₂EO are present in aquatic environment as wastewater contaminants, and their toxic effects on aquatic species have been reported. Apoptosis has been shown to be induced by serum deprivation or copper treatment. To understand the toxicity of nonylphenol diethoxylate, we investigated the effects of NP₂EO on apoptosis induced by serum deprivation and copper by using PC12 cell system. Nonylphenol diethoxylate itself showed no toxicity and recovered cell viability from apoptosis. In addition, nonylphenol diethoxylate decreased DNA fragmentation caused by apoptosis in PC12 cells. This phenomenon was confirmed after treating apoptotic PC12 cells with nonylphenol diethoxylate, whereas the cytochrome c release into the cytosol decreased as compared to that in apoptotic cells not treated with nonylphenol diethoxylates. Furthermore, Bax contents in apoptotic cells were reduced after exposure to nonylphenol diethoxylate. Thus, nonylphenol diethoxylate has the opposite effect on apoptosis in PC12 cells compared to nonylphenol, which enhances apoptosis induced by serum deprivation. The difference in structure of the two compounds is hypothesized to be responsible for this phenomenon. These results indicated that nonylphenol diethoxylate has capability to affect cell differentiation and development and has potentially harmful effect on organisms because of its unexpected impact on apoptosis. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1389–1398, 2016.     

Comparison of the effects of valproic acid and levetiracetam on apoptosis in the human ovarian cancer cell line OVCAR-3

BackgroundWe have previously shown that due to its cytotoxic and cytostatic activities, valproic acid (VPA), but not levetiracetam (LEV), may have potential as a drug for treating human ovarian cancer. In the present study, we compare apoptotic mechanisms including gene and protein expression in the human ovarian cancer cell line, OVCAR-3, following exposure to VPA and LEV.MethodsCells were cultured with VPA or LEV at concentrations between 0.1 mM and 10 mM. Apoptosis was assessed by DNA fragmentation assay and expression of apoptosis-regulatory genes determined by real-time PCR and confirmed by western blotting. Time-dependent effects of VPA and LEV on activity of caspases (-3, -8 and -9) activity were evaluated by fluorescent assay and western blotting.ResultsExposure to VPA at concentrations above 5 mM resulted in an increase in DNA fragmentation, modulated expression of genes and proteins associated with apoptosis and activated caspase ca scade. Exposure to LEV, however, did not affect DNA fragmentation and modulation of the mechanisms of apoptosis was not observed in LEV-treated cells at all doses used.ConclusionsExposure to high concentrations of VPA significantly stimulated apoptosis, by modulating the expression of genes and proteins responsible for cell death and also by activation of caspases cascade. Such effects were not observed with LEV. These data suggest that VPA should be seriously evaluated as an anti-cancer drug for ovarian cancer.     

Propyl gallate-induced DNA fragmentation in isolated rat hepatocytes

Incubation of isolated rat hepatocytes with propyl gallate (PG) at concentrations of ≥1 mM induced cell killing, whereas PG at ≤0.5 mM did not cause cell death during a 3-h incubation. PG at ≥0.5 mM elicited the ladder formation of soluble low-molecular weight DNA fragments with integer multiples of approximately 180 bp and specific nuclear DNA cleavages detected cytopathologically by labeling of a digoxigenin-nucleotide complex to new 3′-OH ends. Both of these PG-induced changes observed in hepatocytes are characteristic features of apoptosis. In contrast, the pretreatment of N-acetylcysteine (4 mM), a precursor of intracellular glutathione (GSH) and antioxidant, prevented PG (0.5 mM)-induced formation of soluble DNA fragments and loss of cellular GSH, ATP, and formation of blebbing. These results suggest that when the concentration of PG is decreased, the effects of PG on hepatocytes change from acute necrotic to apoptotic mode, and that the onset of DNA fragmentation is associated with GSH depletion. Received: 23 June 1997 / Accepted: 18 August 1997     

Aspirin and sodium salicylate inhibit proliferation and induce apoptosis in rheumatoid synovial cells

Aspirin has been reported to induce apoptosis in a variety of cell lines. In this study, we examined whether aspirin and sodium salicylate inhibit cell growth and induce apoptosis in rheumatoid synovial cells. Synovial cells were obtained from patients with rheumatoid arthritis, and the cells were treated with aspirin or sodium salicylate (0.1-10 mM) for 24 h. Cell proliferation and viability were assessed by 5-bromo-2'-deoxyuridine incorporation and by 4-[3-(4-iodophenyl)-2-(4-nitrophenyl)-2H-5-tetrazolio]-1,3-benzene disulfonate (WST-1) assay, respectively. The apoptosis of synovial cells was identified by DNA fragmentation assay and terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (TUNEL) assay. Aspirin and sodium salicylate suppressed the proliferation (IC50 (concentration causing 50% inhibition of cell proliferation): 2.1 and 1.2 mM, respectively) and reduced the viability (IC50: 2.0 and 1.4 mM, respectively) of synovial cells in a concentration-dependent manner at 0.3-10 mM. Furthermore, they induced DNA fragmentation and increased the number of TUNEL-positive synovial cells. These results suggest that aspirin and sodium salicylate can inhibit the proliferation of rheumatoid synovial cells through induction of apoptosis.     

Reduced concentrations of serum enhance the antiproliferative activity of retinoid-related molecules and accelerate the onset of apoptosis

Retinoid-related molecules (RRMs) that are selective agonists for the retinoic acid receptor-gamma and one retinoid antagonist are potent inducers of apoptosis in various cancer cell lines. This cell-killing activity makes them promising candidates for their use as anticancer drugs. We have observed that reducing the amount of serum in the cell culture medium significantly increased the antiproliferative activity of these RRMs in a serum concentration dependent manner. The induction of caspase activity, DNA fragmentation, and externalization of phosphatidylserine by the RRMs was markedly reduced when cells were treated in medium containing 10% serum, as compared to cells treated in low serum. High concentrations of serum also inhibited the activation of stress kinases by RRMs and higher amounts of the retinoid derivatives were necessary to cause quantitatively similar effects as compared to treatments in medium containing low serum. We have demonstrated that high concentrations of serum in the culture medium prevented the intracellular accumulation of MX3350-1 (agonist). Moreover, pre-incubation of cells in low serum-containing medium accelerated the onset of apoptosis as evidenced by the rapid activation of caspases and formation of apoptotic bodies. The release of cytochrome c and Smac induced by RRMs occurred earlier in cells that had been pre-incubated in 0.5% serum, while the activation of JNK and p38 stress kinases was unaffected.     

Scutellarin protects PC12 cells from oxidative stress-induced apoptosis

The present study investigated the effects of scutellarin on oxidative stress-induced cell apoptosis in PC12 cells. Exposure of cells to hydrogen peroxide (H₂O₂) triggered a typical apoptosis, as evidenced by DNA fragmentation, DNA loss and externalization of phosphatidylserine (PS). This treatment also caused significant elevation of oxidative stress characterized by intracellular accumulations of reactive oxygen species (ROS) and malondialdehyde (MDA), a product of lipid peroxidation. Preincubation of cells with scutellarin significantly inhibited the fragmentation and loss of DNA, the externalization of PS, and decreased the percentage of cell apoptosis. Also, intracellular accumulations of ROS and MDA resulting from H₂O₂ exposure were significantly reduced by scutellarin. These findings suggest that scutellarin exerts significant protection against oxidative stress-induced apoptosis, which might be beneficial for the prevention and treatment of oxidative stress-mediated disorders.     

Scutellarin protects PC12 cells from oxidative stress-induced apoptosis

The present study investigated the effects of scutellarin on oxidative stress-induced cell apoptosis in PC12 cells. Exposure of cells to hydrogen peroxide (H2O2) triggered a typical apoptosis, as evidenced by DNA fragmentation, DNA loss and externalization of phosphatidylserine (PS). This treatment also caused significant elevation of oxidative stress characterized by intracellular accumulations of reactive oxygen species (ROS) and malondialdehyde (MDA), a product of lipid peroxidation. Preincubation of cells with scutellarin significantly inhibited the fragmentation and loss of DNA, the externalization of PS, and decreased the percentage of cell apoptosis. Also, intracellular accumulations of ROS and MDA resulting from H2O2 exposure were significantly reduced by scutellarin. These findings suggest that scutellarin exerts significant protection against oxidative stress-induced apoptosis, which might be beneficial for the prevention and treatment of oxidative stress-mediated disorders.     

Prostanoids regulate proliferation of vascular smooth muscle cells induced by arginine vasopressin

We investigated the effects of low concentrations of nitric oxide (NO) on cell viability using NO donors, (+/-)-(E)-4-methyl-2-[(E)-hydroxyimino]-5-nitro-6-methoxy-3-hex enamid e (NOR1), (+/-)-(E)-4-methyl-2-[(E)-hydroxyimino]-5-nitro-3-hexenamide (NOR2), (+/-)-(E)-4-ethyl-2-[(E)-hydroxyimino]-5-nitro-3-hexenamide (NOR3) and (+/-)-N-[(E)-4-ethyl-2-[(Z)-hydroxyimino]-5-nitro-3-hexen-1- yl]-3-pyr idine (NOR4). The half-life times of the NO release from these four NOR analogs, NOR1, NOR2, NOR3 and NOR4, were determined (6.5, 84, 105 and 340 min, respectively) by using 4,5-diaminofluorescein (DAF-2), a newly developed indicator of NO. Exposure of undifferentiated PC12 cells to low concentrations of NO donors, NOR2 or NOR3 (1-100 microM), but not NOR1 nor NOR4, resulted in cell death in a dose- and time-dependent manner, as determined from cell viability assessed by 3-(4,5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H-tetrazolium (MTT) assay. After 24 h exposure to 50 microM NOR2 or NOR3, more than 90% of PC12 cells had died. Furthermore, while the toxic effect of NOR3 was attenuated by replacing the medium at 20 min, 1 or 2 h after drug addition, it was continued by replacing the medium at 3 h or later after drug addition. The cell death was characterized by DNA degradation, nuclear condensation and fragmentation, suggesting apoptosis-like cell death. Pretreatment with an antioxidant ascorbic acid (0.1-0.5 mM) completely prevented the cell death caused by NOR3, while glutathione (0.1-0.2 mM) and cysteine (0.2-0.4 mM) provided partial protection. These findings suggest that the cell toxicity induced by NO at low concentrations strongly depends upon the duration of expose to NO from NO donors, and these toxic effects are effectively prevented by the antioxidant, ascorbic acid.     

The Involvement of Microtubular Disruption in Methylmercury-Induced Apoptosis in Neuronal and Nonneuronal Cell Lines

Methylmercury (MeHg) is known to interfere with cell cycle progression by disruption of microtubules. The relationship between the changes in cell cycle and the induction of apoptosis caused by MeHg was investigated in cultured mammalian cells. MeHg caused nuclear fragmentation and DNA ladder formation in rat pheochromocytoma (PC12) and mouse neuroblastoma cells exposed to MeHg. Flow cytometric analysis revealed that the occurrence of apoptosis was preceded by the accumulation of cells in G2/M after MeHg treatment. Exposure to colchicine, a well-characterized mitotic inhibitor, also caused G2/M-phase arrest followed by the appearance of apoptotic cells. These results suggest that G2/M-phase arrest through the disruption of microtubules is an important event in the development of apoptosis by MeHg. MeHg treatment led to G2/M-phase arrest followed by apoptosis in nonneuronal HeLa cells also. Bcl-2 was phosphorylated by MeHg treatment in HeLa cells but not in PC12 cells; however, p53 expression was not changed in either cell line. Thus, MeHg induces apoptosis via a p53-independent pathway in both cell lines, however, different pathways may be activated after the disruption of microtubules in PC12 and HeLa cells.     

A superoxide anion-scavenger, 1,3-selenazolidin-4-one suppresses serum deprivation-induced apoptosis in PC12 cells by activating MAP kinase

Synthetic organic selenium compounds, such as ebselen, may show glutathione peroxidase-like antioxidant activity and have a neurotrophic effect. We synthesized 1,3-selenazolidin-4-ones, new types of synthetic organic selenium compounds (five-member ring compounds), to study their possible applications as antioxidants or neurotrophic-like molecules. Their superoxide radical scavenging effects were assessed using the quantitative, highly sensitive method of real-time kinetic chemiluminescence. At 166 μM, the O₂⁻ scavenging activity of 1,3-selenazolidin-4-ones ranged from 0 to 66.2%. 2-[3-(4-Methoxyphenyl)-4-oxo-1,3-selenazolidin-2-ylidene]malononitrile (compound b) showed the strongest superoxide anion-scavenging activity among the 6 kinds of 2-methylene-1,3-selenazolidin-4-ones examined. Compound b had a 50% inhibitory concentration (IC₅₀) at 92.4 μM and acted as an effective and potentially useful O₂⁻ scavenger in vitro. The effect of compound b on rat pheochromocytome cell line PC12 cells was compared with that of ebselen or nerve growth factor (NGF) by use of the MTT [3-(4, 5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide] assay. When ebselen was added at 100 μM or more, toxicity toward PC12 cells was evident. On the contrary, compound b suppressed serum deprivation-induced apoptosis in PC12 cells more effectively at a concentration of 100 μM. The activity of compound b to phosphorylate mitogen-activated protein kinase/extracellular signal-regulated protein kinase (ERK) 1/2 (MAP kinase) in PC12 cells was higher than that of ebselen, and the former at 100 μM induced the phosphorylation of MAP kinase to a degree similar to that induced by NGF. From these results, we conclude that this superoxide anion-scavenger, compound b, suppressed serum deprivation-induced apoptosis by promoting the phosphorylation of MAP kinase.     

gp120 of HIV-1 induces apoptosis in rat cortical cell cultures: prevention by memantine.

After incubation of rat cortical cell cultures with the human immunodeficiency virus type 1 (HIV-1) coat protein gp120 for 12 h, cells showed fragmentation of DNA at internucleosomal linkers, the characteristic feature of apoptosis. In a quantitative approach, it was determined that the percentage of DNA fragmentation increased from 7%, in the absence of gp120, to 62% following incubation with 24 ng/ml of gp120. Simultaneously, the percentage of viable cells decreased from 94% to 33%. Memantine (1-amino-3,5-dimethyladamantane), a drug currently used in the therapy of spasticity and Parkinson's disease as well as the NMDA antagonist MK-801 both prevented the effects of gp120 at micromolar concentrations. In human cultured astrocytes, gp120 was ineffective with respect to DNA fragmentation and cell toxicity. From these data, we conclude that the gp120-induced apoptosis may contribute to the neurological complications frequently associated with the immunodeficiency syndrome. The cytoprotective effect of memantine in cortical cell cultures may qualify the drug for the treatment of AIDS-related dementia.