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L Z Liu

Publications and source records attributed to L Z Liu.

At least 19 recordsLinked to original sources
PubMed2001

Peroxisome proliferator-activated receptor agonists prevent 25-OH-cholesterol induced c-jun activation and cell death.

BACKGROUND: Cholesterol oxides, the oxygenated derivatives of cholesterol, have been shown to cause programmed cell death in a variety of cell types. Using N9 microglia, this study was designed to investigate the molecular events induced by cholesterol oxides prior to the execution of programmed cell death. RESULTS: Microglia were very sensitive to 25-OH-cholesterol, such that a 2-day treatment of the cells with 5 microM 25-OH-cholesterol reduced cell viability to 5-10% of controls. There was a dose- and time-dependent increase in c-jun and phospho-c-jun levels in microglia prior to this 25-OH-cholesterol induced cell death. In contrast, 7-beta-OH-cholesterol, which was relatively non-toxic to microglia, did not increase phospho-c-jun levels. Peroxisome proliferator-activated receptors (PPARs) are a group of nuclear receptors that have important roles in atherogenesis. Results from this study indicate that PPAR agonists such as 15d-PGJ2, indomethacin and WY14643 can attenuate cholesterol oxide induced c-jun activation and cell death in microglia. CONCLUSIONS: Peroxisome proliferator-activated receptor agonists may be useful in future development of pharmacological agents against cholesterol oxide induced cytotoxicity.

Animals↗
PubMed2001

Polymer-assisted formation of giant polyoxomolybdate structures.

A highly ordered, porous nanoscale network structure of polyoxomolybdate was prepared from the slow decomposition of an unstable precursor compound MoO(2)(OH)(OOH) in the presence of PEO-containing triblock copolymer gels or semidilute/concentrated poly(ethylene oxide) (PEO) homopolymer solutions. Small-angle X-ray scattering (SAXS) and wide-angle X-ray diffraction (WAXD) measurements of the 1-microm size crystals revealed an extremely ordered primitive cubic (pc) structure made of polyoxomolybdates. Scanning electron microscopy (SEM) measurements showed that the overall size of these single crystals was close to 1 microm, in agreement with estimates from the scattering peak widths. Evidence from both scattering measurements and transmission electron microscope (TEM) measurements suggested that the system formed a highly porous primitive cubic network similar to that of certain zeolite structures. However, the observed lattice constant of 5 nm was much larger. The function of the PEO-containing polymer network was found to be very subtle and complex. Presumably, PEO acted simultaneously as a weak reducing agent and as a viscous matrix to ensure sufficient time for the formation of long-range ordered structures, resulting in the growth of extremely uniform but probably hollow "nanospheres". We suggest that this new material may find unique applications as a high-efficiency absorbent or catalyst. Furthermore, the current synthetic method may open up new pathways to prepare similar functional nanomaterials.

Journal Article↗
PubMed2000

Catecholamines inhibit microglial nitric oxide production.

Viral infection in the central nervous system can induce nitric oxide production, which serves as a major host defense against viral infection. Under stress, catecholamine secretion is enhanced and immune responses are diminished in animals. Using N9 microglial cells, this study tested the effect of catecholamines on microglial nitric oxide production. Results indicated that each member of the catecholamine family (dopamine, norepinephrine and epinephrine) was a potent inhibitor of the microglial nitric oxide production. In contrast, dopa, the immediate precursor of the catecholamine biosynthesis pathway, was a weak inhibitor, except at very high concentrations. The inhibitory effect of catecholamines was mimicked by an alpha-adrenergic receptor agonist (phenylephrine) and by a beta-adrenergic receptor agonist (isoproterenol), but not by forskolin or analogs of cyclic adenosine monophosphate. Western blot analysis indicated that catecholamines caused a slight decrease in the formation of inducible nitric oxide synthase. These results suggest that catecholamines have the ability to block nitric oxide production by microglia, which could partially explain the impaired immune protection against viral infection in the central nervous system in stressed animals.

Adrenergic Agonists↗
PubMed2000

Inhibition of microglial nitric oxide production by hydrocortisone and glucocorticoid precursors.

Viral and bacterial infection in the central nervous system can induce nitric oxide production, which serves as a major host defense against invading microorganisms. Glucocorticoids secretion is enhanced and immune responses are diminished in stressed animals or in patients suffering depression. Using N9 microglial cells, this study tested the hypothesis that glucocorticoids and their precursors caused an impaired immune defense in animals because these compounds could inhibit microglial nitric oxide production. Results indicated that both hydrocortisone and the synthetic glucocorticoid, dexamethasone, were potent inhibitors of the microglial nitric oxide production. While glucocorticoid precursors were not as potent as hydrocortisone, the potency of these precursors increased linearly as they advanced on the biosynthesis pathway. Northern and Western blot analyses indicated that hydrocortisone and dexamethasone might interfere with the inducible nitric oxide synthase at either the transcription or at the post-translational level, depending on the concentrations used. These results suggest that glucocorticoids have the ability to block nitric oxide production by microgila, which could partially explain the impaired immune protection against infection in the central nervous system in stressed animals.

Animals↗
PubMed1999

Manganese potentiates nitric oxide production by microglia.

Manganese toxicity has been associated with clinical symptoms of neurotoxicity which are similar to the symptoms observed in Parkinson's disease. Earlier reports indicated that reactive microglia was present in the substantia nigra of patients with Parkinson's disease. Using N9 microglial cells, the current study was designed to determine whether high levels of manganese were associated with microglial activation. Results indicated that manganese significantly increased the bacterial lipopolysaccharide-induced nitric oxide production. This potent activity of manganese was not shared by other transition metals tested, including iron, cobalt, nickel, copper and zinc. Immunohistochemical staining and Western blot analysis indicated that manganese increased the cellular production of inducible nitric oxide synthase. Northern blot analysis indicated that manganese likely increased iNOS gene transcription since this agent increased the mRNA level of the inducible nitric oxide synthase. In contrast to other transition metals tested, manganese did not appear to be cytotoxic to microglial cells. These results suggested that manganese could induce sustained production of neurotoxic nitric oxide by activated microglial cells, which might cause detrimental consequences to surrounding neurons.

Animals↗
PubMed1998

Cholesterol oxides induce programmed cell death in microglial cells.

N9 microglial cells were used as a model to examine the effect of cholesterol oxides on central nervous system microglia. Results indicated that 25-OH-cholesterol was the most cytotoxic agent among the cholesterol oxides tested. During the process of cell death, this agent caused prominent nuclei condensation and significant DNA fragmentation, a phenomenon association with programmed cell death. Cholesterol oxides were able to potentiate the bacterial lipopolysaccharide (LPS)-induced nitric oxide production to various degrees. Consistent with this finding, Northern blot analysis indicated that 25-OH-cholesterol potentiated the LPS-induced nitric oxide synthase RNA levels. The cytotoxicity of 25-OH-cholesterol could be prevented by methyl-beta-cyclodextrin, a glucose polymer known to cause cholesterol oxide efflux from cells. While much attention has been focused on the cytotoxicity of cholesterol oxides on immune cells within the blood, including lymphocytes and macrophages, the results from this study indicated for the first time that these agents are toxic to microglial cells derived from the central nervous system.

Animals↗
PubMed1998

Neurotoxicity of cholesterol oxides on cultured cerebellar granule cells.

Cultured rat cerebellar granule cells were used to determine the potential neurotoxicity of cholesterol oxides. The cholesterol oxides tested included: 7-beta-OH-, 7-keto-, 19-OH-, 22(R)-OH-, 22(S)-OH- and 25-OH- cholesterol. Among them, 7-beta-OH- and 7-keto-cholesterol were the most efficacious in causing neuronal death such that 20 microg/ml (50 microM) of these agents killed more than 80% of cells in 2 days. 7-beta-OH-cholesterol at this concentration killed 50% of cells in approximately 7 h. A number of pharmacological agents were tested for their abilities to prevent neuronal death induced by cholesterol oxides. Among them, aurintricarboxylic acid, vitamin E and methyl-beta-cyclodextrin were able to prevent cholesterol oxide-induced neurotoxicity in a dose-dependent manner. These results suggest that, in addition to causing pathological changes in cells directly involved in atherosclerosis, cholesterol oxides may induce toxicity in neurons of the central nervous system.

Animals↗
PubMed1998

Neurotoxicity of 25-OH-cholesterol on NGF-differentiated PC12 cells.

PC12 cells induced to differentiate with nerve growth factor were used to study the neurotoxicity of 25-OH-cholesterol. This agent induced a dose- and time-dependent cell death in neuronal PC12 cells. Cells treated with this agent showed condensed nuclei, a morphology similar to that of cells dying of programmed cell death. However, agents known to prevent neuronal programmed cell death (cyclic AMP, KCl, aurintricarboxylic acid, and cycloheximide) failed to prevent the 25-OH-cholesterol-mediated cytotoxicity. On the other hand, cell death induced by 25-OH-cholesterol was prevented by treatment with vitamin E and methyl-beta-cyclodextrin. In contrast to observations made in other cell types, whole-cell patch clamp recording of neuronal PC12 cells revealed that treatment with 25-OH-cholesterol did not significantly alter calcium influx through voltage-dependent channels. These results provide the first characterization of the toxicity of cholesterol oxides toward neuronal PC12 cells, which should be useful in future studies on the interactions between cholesterol oxides and cells from the nervous system.

Animals↗
PubMed1998

Toxicity of cholesterol oxides on cultured neuroretinal cells.

PURPOSE: By using nerve growth factor-differentiated PC12 cells as a model for sympathetic neurons, we have recently shown that cholesterol oxides are toxic to cells of neural origin. Since lipid metabolism is known to be involved in some pathological conditions associated with the visual system, we sought to extend this line of research by studying the potential cytotoxicity of cholesterol oxides on primary cultures derived from neuroretinas. METHODS: Dissociated cultures derived from neuroretinas of 1-day-old Sprague-Dawley rats were used in this series of studies. Immunohistochemical staining was used to identify neuronal and glial cell types in these cultures. MTT assay was used to determine the cytotoxicity of cholesterol oxides, including 7-beta-OH-, 7-keto-, 19-OH-, 22(R)-OH-, 22(S)-OH- and 25-OH-cholesterol. RESULTS: Among the cholesterol oxides tested, 7-beta-OH- and 7-keto-cholesterol were the most effective in causing cell death, such that 20 micrograms/ml (50 microM) of these agents killed approximately 80% of cells in 3 days. A time-dependent experiment indicated that 10 micrograms/ml of 7-beta-cholesterol was able to kill 50% of cells in approximately 5 h. A number of pharmacological agents were tested for their ability to prevent cell death induced by cholesterol oxides. Among them, vitamin E and methyl-beta-cyclodextrin were able to prevent cholesterol oxide-induced cell death in a dose-dependent manner. CONCLUSIONS: These results suggest that, in addition to causing pathological changes in cells directly involved in atherosclerosis, cholesterol oxides may be toxic to cells derived from neuroretinas.

Animals↗
PubMed1997

Establishment of two morphologically distinct PC12 cell lines resistant to 25-OH-cholesterol toxicity.

Two novel populations of spontaneous PC12 cell mutants resistant to a toxic concentration of 25-OH-cholesterol (5 microg/ml, 12.5 microM) were isolated and designated as R25R and F25R based on cell morphology. R25R consisted of round cells that were morphologically similar to the parent PC12 cells, and responded to nerve growth factor by extending neurites. F25R was a group of process-bearing flat cells that did not assume a neuronal morphology in the presence of nerve growth factor. These two cell lines also acquired some cross-resistance toward other cholesterol oxides. Nerve growth factor induced prominent voltage-dependent calcium currents in parent PC12 cells and in R25R, but not in F25R. Further experiments indicated that the parent PC12 cells, R25R and F25R exhibited different properties when challenged with a variety of toxic insults, including amphotericin B, serum withdrawal and beta-amyloid protein treatment.

Amyloid beta-Peptides↗
PubMed1997

25-Hydroxycholesterol causes death but does not prevent nerve growth factor-induced neurite outgrowth in PC12 cells.

The effects of cholesterol oxides on regular and neuronal PC12 cells were examined. Among the cholesterol oxides tested, 7-beta-, 22(R)- and 25-OH-cholesterol were very toxic to regular PC12 cells such that approximately 80% of cells were killed after a 3 day incubation with 20 micrograms/ml (50 microM) of these agents. Cholesterol oxides caused cytotoxicity in neuronal PC12 cells at concentrations higher than those observed for regular PC12 cells. The nerve growth factor (NGF)-induced neurite outgrowth and nitric oxide synthase expression appeared normal in PC12 cells treated with a sublethal dose of 25-OH-cholesterol. Neurite regeneration from established neuronal PC12 cells was not inhibited by the presence of a toxic dose of 25-OH-cholesterol. Given the fact that 25-OH-cholesterol is a potent inhibitor of cholesterol synthesis pathway, these results suggest that the de novo synthesis of cholesterol may not be required for NGF-induced neurite outgrowth in PC12 cells.

Animals↗
PubMed1996

The enzymatic activity of Drosophila AWD/NDP kinase is necessary but not sufficient for its biological function.

The Drosophila abnormal wing discs (awd) gene encodes the subunit of a protein that has nucleoside diphosphate kinase (NDP kinase) activity. Null mutations of the awd gene cause lethality after puparium formation. Larvae homozygous for such mutations have small imaginal discs, lymph glands, and brain lobes. Neither the imaginal discs nor the ovaries from such null mutant larvae are capable of further growth or normal differentiation when transplanted into suitable host larvae. This null mutant phenotype can be entirely rescued by one copy of a transgene that has 750 bp of awd upstream regulatory DNA fused to a full-length awd cDNA. Tissue-specific expression of AWD protein from this rescue transgene is identical to tissue-specific expression of beta-galactosidase from a reporter transgene that has the same regulatory region fused to the bacterial lac Z gene. However, this rescue transgene or reporter transgene expression pattern is only a subset of the endogenous pattern of expression detected by either in situ hybridization or immunohistochemistry. This suggests that awd is normally expressed in some tissues where it is not required. The null mutant phenotype cannot be rescued at all by a transgene that has 750 bp of awd upstream regulatory DNA fused to a full-length awd cDNA with a mutation that eliminates NDP kinase activity by replacement of the active site histidine with alanine. This suggests that the enzymatic activity of the AWD protein is necessary for its biological function. The human genes nm23-H1 and nm23-H2 encode NDP kinase A and B subunits, respectively. The protein subunit encoded by either human nm23 gene is 78% identical to that encoded by the Drosophila awd gene. Transgenes that have the 750-bp awd upstream regulatory DNA fused to human nm23-H2 cDNA but not to nm23-H1 cDNA can rescue the imaginal disc phenotype and the zygotic lethality caused by homozygosis for an awd null mutation as efficiently as an awd transgene. However, rescue of female sterility requires twice as much nm23-H2 expression as awd expression. This implies that the enzymatic activity of the AWD protein is not sufficient for its biological function. The biological function may require nonconserved residues of the AWD protein that allow it to interact with other proteins.

Animals↗
PubMed1993

The expression of the Drosophila awd gene during normal development and in neoplastic brain tumors caused by lgl mutations.

The abnormal wing discs (awd) gene of Drosophila is homologous to the nm23 gene of mammals, a gene whose expression is altered in metastatic tumors. Both awd and nm23 encode nucleoside diphosphate kinases (NDP kinases). We have examined the accumulation of AWD/NDP kinase during normal development by assaying enzyme activity in extracts. There is a nearly constant level of activity throughout larval and pupal development. We have examined the tissue-specific transcription of the awd gene by RNA in situ hybridization and by reporter gene expression. In imaginal discs and brains there is no detectable awd gene expression until the beginning of the third larval instar, despite the constant level of enzyme activity measured in extracts of larvae and pupae. The most intense awd gene expression in imaginal discs and brains occurs after the end of larval development. We have also examined awd gene expression in neoplastic brain tumors caused by mutations in the lethal giant larvae (lgl) gene. In lgl mutant brains, as in normal brains, awd gene expression begins during the third larval instar. No tumors form in brains from lgl-; awd- double mutant larva, so awd gene expression is required for tumor formation and/or proliferation. There is more accumulation of AWD/NDP kinase in lgl- mutant brains than there is in normal brains. Using an awd reporter gene, we show that this is a consequence of an increased proportion of awd gene-expressing cells in mutant brains. Using the same awd reporter gene as a marker of donor cells, we have confirmed the invasiveness of lgl-induced neuroblastomas.

Animals↗
PubMed1991

The gene for von Recklinghausen neurofibromatosis (NF1) maps to the pericentromeric region of chromosome 17 in Chinese families.

Linkage analysis of six Chinese families with neurofibromatosis type 1 (NF1) confirms the location of the NF1 gene to the region of the proximal long arm of chromosome 17, as in Caucasian populations. The diagnosis of NF1 was made according to internationally accepted criteria. The markers used were D17S71, D17S58, D17S33, and EVI2A. The overall odds in favor of NF1 lying within this linkage group in the families studied are over 150,000:1, with a maximum location score of 5.112 for the interval D17S58-EVI2A.

Centromere↗
PubMed1989

[Chemical studies on the constituents of radix Ophiopogonis].

In this paper four compounds isolated from Radix Ophiopogonis are described. Their structures have been identified as beta-sitosterol (I), 6-aldehydo-7-methoxy-isoophiopogonanone B (II), beta-sitosterol-beta-D-glucopyranoside (III) and 1-borneol-beta-D-apisyl-beta-D-glucopyranoside (IV) on the basis of spectral data and hydrolytic reaction.

Camphanes↗
PubMed1989

[Comparison in susceptibility of Anopheles dirus and Anopheles stephensi to B strain of Plasmodium cynomolgi].

This paper reports on the comparative susceptibility of A. dirus (Hainan strain) and A. stephensi (Hor strain) to the B strain of P. cynomolgi in paired feeding experiments. In the most susceptible infective period, the infection rate in midgut and salivary gland of the two species was over 90%, the difference is not statistically significant. In relatively infective period, three experiments were performed, the infection rate in midgut of A. dirus was 24.4-60.4% with an average of 46.5% (53/114), and that of A. stephensi was 11.5-21.1% with an average of 14.2% (16/113). Statistically, experiment I showed no significant difference, the difference in experiment II was highly significant (P less than 0.01), and that in experiment III was significant (P less than 0.05). The number of oocysts in A. dirus was three times over that in A. stephensi. The infection rate of salivary gland in A. dirus was 18.2-55.0% with an average of 30.6% (19/62) and that of A. stephensi was 6.7-14.3% with an average of 9.5% (6/63). Statistically, only one of the three experiments showed significant difference (P less than 0.01). The result suggests that the susceptibility of A. dirus is higher than that of A. stephensi to the B strain of Plasmodium cynomolgi.

Animals↗