15 results on '"Lin Liu"'
Search Results
2. Active intracellular domain of notch enhances transcriptional activation of CCAAT/enhancer binding protein beta on a rat pregnancy-specific glycoprotein gene
- Author
-
Hungwen Chen, Yichuen Chong, and Chia-Lin Liu
- Subjects
Biochemistry -- Research ,Carrier proteins -- Research ,Glycoproteins -- Research ,Placenta -- Research ,Gene expression -- Research ,Biological sciences ,Chemistry - Abstract
Research has been conducted on the pregnancy-specific glycoproteins expressed in the placenta. The characterization of the rodent PSG gene promoter elements is described.
- Published
- 2000
3. Redox reactions of the [alpha]-synuclein-[Cu.sup.2+] complex and their effects on neuronal cell viability
- Author
-
Chengshan Wang, Lin Liu, Lin Zhang, Yong Peng, and Feimeng Zhou
- Subjects
Mass spectrometry -- Usage ,Organocuprates -- Structure ,Organocuprates -- Chemical properties ,Oxidative stress -- Analysis ,Parkinson's disease -- Genetic aspects ,Parkinson's disease -- Physiological aspects ,Peptides -- Chemical properties ,Peptides -- Structure ,Biological sciences ,Chemistry - Abstract
Electrospray-mass spectrometry (ES?MS) was employed to confirm the formation of the [Cu.sup.2+] complex with [alpha]-syn or with an N-terminal peptide, [alpha]-synuclein which play an important role in neuropathology in ParkinsonEs disease (PD). The results provide insight into partial role of oxidative stress for the loss of dopaminergic cells in PD brain and the multifaceted role of the [alpha]-syn-[Cu.sup.2+] complex in oxidative stress associated with PD symptoms.
- Published
- 2010
4. Kinetics of inhibition of beta-amyloid aggregation by transthyretin
- Author
-
Lin Liu and Murphy, Regina M.
- Subjects
Alzheimer's disease -- Research ,Amyloid beta-protein -- Research ,Proteolysis -- Analysis ,Biological sciences ,Chemistry - Abstract
Results of the biophysical analysis of A(beta) aggregation kinetics in the presence of transthyretin are presented. The findings support a hypothesis wherein transthyretin preferentially binds to aggregated rather than monomeric A(beta), hampering the growth of the aggregates.
- Published
- 2006
5. Syntaxin 2 and SNAP-23 are required for regulated surfactant secretion
- Author
-
Abonyo, Barack O., Gou, Deming, Wang, Pengcheng, Narasaraju, Telugu, Lin, Liu, and Wang, Zhixi
- Subjects
Gene expression -- Research ,Biochemistry -- Research ,Pulmonary surfactant -- Research ,Biological sciences ,Chemistry - Abstract
The secretion of lung surfactant in alveolar type II cells is studied. Report depict syntaxin 2 and SNAP-23 expression in alveolar type II cells that are required for regulation of surfactant secretion.
- Published
- 2004
6. Characterization of Protein Kinase C θ Activation Loop Autophosphorylation and the Kinase Domain Catalytic Mechanism
- Author
-
Lin Liu, Ron Kriz, Rita Greco, Mark Stahl, Karl Malakian, Divya Chaudhary, Robert M. Czerwinski, Laura Lin, Scott Wolfrom, Ann Aulabaugh, Stephane Olland, and Ying Huang
- Subjects
Threonine ,Molecular Sequence Data ,Biology ,Mitogen-activated protein kinase kinase ,Binding, Competitive ,Biochemistry ,Catalysis ,Substrate Specificity ,MAP2K7 ,Adenosine Triphosphate ,Catalytic Domain ,Serine ,ASK1 ,Amino Acid Sequence ,c-Raf ,Phosphorylation ,Kinase activity ,Protein Kinase C ,MAP kinase kinase kinase ,Osmolar Concentration ,Autophosphorylation ,Phosphoproteins ,Recombinant Proteins ,Cell biology ,Adenosine Diphosphate ,Enzyme Activation ,Isoenzymes ,Kinetics ,Protein Kinase C-theta ,Mutagenesis, Site-Directed ,Cyclin-dependent kinase 9 - Abstract
Protein kinase C theta (PKCtheta), a member of the Ca(2+)-independent novel subfamily of PKCs, is required for T-cell receptor (TCR) signaling and IL2 production. PKCtheta-deficient mice have impaired Th2 responses in a murine ova-induced asthma model, while Th1 responses are normal. As an essential component of the TCR signaling complex, PKCtheta is a unique T-cell therapeutic target in the specific treatment of T-cell-mediated diseases. We report here the PKCtheta autophosphorylation characteristics and elucidation of the catalytic mechanism of the PKCtheta kinase domain using steady-state kinetics. Key phosphorylated residues of the active PKCtheta kinase domain expressed in Escherichia coli were characterized, and mutational analysis of the kinase domain was performed to establish the autophosphorylation and kinase activity relationships. Initial velocity, product inhibition, and dead-end inhibition studies provided assignments of the kinetic mechanism of PCKtheta(362)(-)(706) as ordered, wherein ATP binds kinase first and ADP is released last. Effects of solvent viscosity and ATPgammaS on PKCtheta catalysis demonstrated product release is partially rate limiting. Our studies provide important mechanistic insights into kinase activity and phosphorylation-mediated regulation of the novel PKC isoform, PKCtheta. These results should aid the design and discovery of PKCtheta antagonists as therapeutics for modulating T-cell-mediated immune and respiratory diseases.
- Published
- 2005
7. Active Intracellular Domain of Notch Enhances Transcriptional Activation of CCAAT/Enhancer Binding Protein β on a Rat Pregnancy-Specific Glycoprotein Gene
- Author
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Chia-Lin Liu, Yichuen Chong, and Hungwen Chen
- Subjects
Intracellular Fluid ,Transcriptional Activation ,Genetic Vectors ,Biology ,Biochemistry ,Genes, Reporter ,Animals ,Humans ,Electrophoretic mobility shift assay ,Cloning, Molecular ,Binding site ,Nuclear protein ,Promoter Regions, Genetic ,Gene ,Transcription factor ,chemistry.chemical_classification ,Receptors, Notch ,Ccaat-enhancer-binding proteins ,Pregnancy-Specific beta 1-Glycoproteins ,Binding protein ,Membrane Proteins ,Nuclear Proteins ,Molecular biology ,Peptide Fragments ,Rats ,DNA-Binding Proteins ,Enhancer Elements, Genetic ,chemistry ,Immunoglobulin J Recombination Signal Sequence-Binding Protein ,COS Cells ,CCAAT-Enhancer-Binding Proteins ,Trans-Activators ,Electrophoresis, Polyacrylamide Gel ,Glycoprotein - Abstract
Pregnancy-specific glycoproteins (PSGs) are primarily expressed in the placenta and become the major glycoproteins at term. To understand the regulation of PSG expression, we characterized the promoter elements of a rodent PSG gene, rnCGM3, and delineated three nuclear protein binding sites: FPI, -II, and -III in the 5'-flanking region of the gene. The FPII-binding factor is shown to be C/EBPbeta, which positively regulates rnCGM3 expression [Chen, H., et al. (1995) DNA Cell Biol. 14, 681-688]. In the current study, we used the yeast one-hybrid system to isolate transcription factors binding to the FPIII site and demonstrated that a rodent J kappa recombination signal sequence binding protein, rRBPJ kappa-2N, bound to the FPIII site. Electrophoretic mobility shift assay with rat placental nuclear proteins revealed a constitutive occupancy of the FPIII site by RBPJ kappa. By transient expression analyses, we demonstrated that rRBPJ kappa-2N repressed the expression from an FPIII-driven SV40 promoter. However, this repression effect was counteracted by the active intracellular domain of Notch (NotchIC). Using the native rnCGM3 promoter construct, we demonstrated that the promoter activity stimulated by C/EBP beta was also repressed by rRBPJ kappa-2N but enhanced by NotchIC. Additionally, we found that NotchIC can stimulate expression through another RBPJkappa site within the FPI site. A functional interaction between factors binding to the FPI, FPII, and FPIII sites is proposed.
- Published
- 2000
8. Redox reactions of the α-synuclein-Cu(2+) complex and their effects on neuronal cell viability
- Author
-
Lin Zhang, Yong Peng, Feimeng Zhou, Chengshan Wang, and Lin Liu
- Subjects
inorganic chemicals ,Stereochemistry ,Cell Survival ,animal diseases ,Dopamine ,Peptide ,Ascorbic Acid ,medicine.disease_cause ,Biochemistry ,Redox ,Article ,chemistry.chemical_compound ,medicine ,Humans ,heterocyclic compounds ,Viability assay ,Hydrogen peroxide ,Alpha-synuclein ,chemistry.chemical_classification ,Neurons ,Parkinson Disease ,Hydrogen Peroxide ,Ascorbic acid ,nervous system diseases ,Oxidative Stress ,chemistry ,nervous system ,alpha-Synuclein ,Peptides ,Oxidation-Reduction ,Oxidative stress ,Copper ,medicine.drug - Abstract
α-Synuclein (α-syn), a presynaptic protein believed to play an important role in neuropathology in Parkinson's disease (PD), is known to bind Cu(2+). Cu(2+) has been shown to accelerate the aggregation of α-syn to form various toxic aggregates in vitro. Copper is also a redox-active metal whose complexes with amyloidogenic proteins/peptides have been linked to oxidative stress in major neurodegenerative diseases. In this work, the formation of the Cu(2+) complex with α-syn or with an N-terminal peptide, α-syn(1-19), was confirmed with electrospray-mass spectrometry (ES-MS). The redox potentials of the Cu(2+) complex with α-syn (α-syn-Cu(2+)) and α-syn(1-19) were determined to be 0.018 and 0.053 V, respectively. Furthermore, the Cu(2+) center(s) can be readily reduced to Cu(+), and possible reactions of α-syn-Cu(2+) with cellular species (e.g., O(2), ascorbic acid, and dopamine) were investigated. The occurrence of a redox reaction can be rationalized by comparing the redox potential of the α-syn-Cu(2+) complex to that of the specific cellular species. For example, ascorbic acid can directly reduce α-syn-Cu(2+) to α-syn-Cu(+), setting up a redox cycle in which O(2) is reduced to H(2)O(2) and cellular redox species is continuously exhausted. In addition, the H(2)O(2) generated was demonstrated to reduce viability of the neuroblastoma SY-HY5Y cells. Although our results ruled out the direct oxidation of dopamine by α-syn-Cu(2+), the H(2)O(2) generated in the presence of α-syn-Cu(2+) can oxidize dopamine. Our results suggest that oxidative stress is at least partially responsible for the loss of dopaminergic cells in PD brain and reveal the multifaceted role of the α-syn-Cu(2+) complex in oxidative stress associated with PD symptoms.
- Published
- 2010
9. Kinetics of inhibition of beta-amyloid aggregation by transthyretin
- Author
-
Regina M. Murphy and Lin Liu
- Subjects
Genetically modified mouse ,Light ,Kinetics ,macromolecular substances ,Plasma protein binding ,Fibril ,medicine.disease_cause ,Biochemistry ,Microscopy, Electron, Transmission ,mental disorders ,medicine ,Amyloid precursor protein ,Humans ,Prealbumin ,Scattering, Radiation ,Mutation ,Amyloid beta-Peptides ,biology ,Chemistry ,P3 peptide ,nervous system diseases ,Transthyretin ,Spectrometry, Fluorescence ,Models, Chemical ,Biophysics ,biology.protein ,Protein Binding - Abstract
Deposition of beta-amyloid (Abeta) fibrils is an early event in the neurodegenerative processes associated with Alzheimer's disease. According to the "amyloid cascade" hypothesis, Abeta aggregation, and its subsequent deposition as fibrils, is the underlying cause of disease. Abeta is a proteolytic product of amyloid precursor protein (APP); several mutations in APP have been identified that are associated with early onset of disease. Transgenic mice overexpressing APP with the Swedish mutation develop numerous plaques but, surprisingly, lack the neurofibrillary tangles and neuronal loss characteristic of Alzheimer's disease, in apparent contradiction of the amyloid cascade hypothesis. However, recent studies suggest that coproduction of sAPPalpha, an alternative proteolytic product of APP, increases synthesis of transthyretin that, in turn, interacts directly with Abeta to inhibit its toxicity. Here we report results from biophysical analysis of Abeta aggregation kinetics in the presence of transthryetin. At substoichiometric ratios, transthyretin drastically decreased the rate of aggregation without affecting the fraction of Abeta in the aggregate pool. Detailed analysis of the data using a mathematical model demonstrated that the decrease in aggregation rate was due to both a decrease in the rate of elongation relative to the rate of initiation of filaments and a decrease in lateral association of filaments to fibrils. Tryptophan quenching data indicated that transthyretin binds weakly to Abeta, with an estimated apparent KS of 2300 M-1. Taken together, the data support a hypothesis wherein transthyretin preferentially binds to aggregated rather than monomeric Abeta and arrests further growth of the aggregates.
- Published
- 2006
10. Syntaxin 2 and SNAP-23 are required for regulated surfactant secretion
- Author
-
Pengcheng Wang, Barack O. Abonyo, Zhixi Wang, Deming Gou, Lin Liu, and Telugu Narasaraju
- Subjects
Male ,Cell Membrane Permeability ,Molecular Sequence Data ,Vesicular Transport Proteins ,Syntaxin 1 ,Nerve Tissue Proteins ,Lamellar granule ,Biology ,Biochemistry ,Exocytosis ,Rats, Sprague-Dawley ,Pulmonary surfactant ,Syntaxin ,Animals ,Secretion ,Amino Acid Sequence ,Qc-SNARE Proteins ,RNA, Messenger ,Cells, Cultured ,Vesicle ,Immune Sera ,Membrane Proteins ,Pulmonary Surfactants ,Oligonucleotides, Antisense ,Qb-SNARE Proteins ,Syntaxin 3 ,Peptide Fragments ,Cell biology ,Rats ,Pulmonary Alveoli ,nervous system ,Antigens, Surface ,Carrier Proteins ,SNARE Proteins ,Subcellular Fractions - Abstract
The secretion of lung surfactant in alveolar type II cells is a complex process involving the fusion of lamellar bodies with the plasma membrane. This process is somewhat different from the exocytosis of hormones and neurotransmitters. For example, it is a relatively slower process, and lamellar bodies are very large vesicles with a diameter of approximately 1 microm. SNARE proteins are the conserved molecular machinery of exocytosis in the majority of secretory cells. However, their involvement in surfactant secretion has not been reported. Here, we showed that syntaxin 2 and SNAP-23 are expressed in alveolar type II cells. Both proteins are associated with the plasma membrane, and to some degree with lamellar bodies. An antisense oligonucleotide complementary to syntaxin 2 decreased its mRNA and protein levels. The same oligonucleotide also inhibited surfactant secretion, independent of secretagogues. A peptide derived from the N-terminus of syntaxin 2 or the C-terminus of SNAP-23 significantly inhibited Ca(2+)- and GTPgammaS-stimulated surfactant secretion from permeabilized type II cells in a dose-dependent manner. Furthermore, introduction of anti-syntaxin 2 or anti-SNAP-23 antibodies into permeabilized type II cells also inhibited surfactant release. Our results suggest that syntaxin 2 and SNAP-23 are required for regulated surfactant secretion.
- Published
- 2004
11. Nitration of annexin II tetramer
- Author
-
William H. Rowan, Lin Liu, and Peng Sun
- Subjects
inorganic chemicals ,Protein subunit ,Blotting, Western ,Biochemistry ,Nitric oxide ,Cell Line ,chemistry.chemical_compound ,Biopolymers ,Tetramer ,Nitration ,Animals ,Humans ,Tyrosine ,Lung ,Annexin A2 ,Nitrates ,Superoxide ,Molecular biology ,Precipitin Tests ,chemistry ,Liposomes ,cardiovascular system ,Cattle ,Electrophoresis, Polyacrylamide Gel ,Peroxynitrite - Abstract
Annexin II tetramer (AII(t)) is a member of the Ca(2+)- and phospholipid-binding protein family and is implicated in membrane fusion during surfactant secretion. It had previously been shown that high concentrations of nitric oxide (NO) inhibit surfactant secretion from lung type II cells. NO reacts with superoxide (O(2)(-)) to form peroxynitrite (ONOO(-)), a tyrosine nitrating agent, which is found in lungs under certain pathological conditions. It is therefore hypothesized that nitration of AII(t) by ONOO(-) may be a mechanism for the NO inhibition of regulated exocytosis. We therefore performed in vitro studies to test effects of ONOO(-) on AII(t). Western blot analysis using anti-nitrotyrosine antibodies showed a dose-dependent nitration of tyrosine residues in AII(t) treated with ONOO(-). Nitration occurred on the core domain of the p36 subunit, as well as on the p11 subunit. ONOO(-) also caused the formation of dimers between p36 and p11 subunits which were stable in the presence of heating, SDS, and beta-mercaptoethanol. AII(t)-mediated liposome aggregation was inhibited by ONOO(-) with an IC(50) of approximately 30 microM. The inhibition was abolished by urate (a scavenger of ONOO(-) and *OH), but not by mannitol (a scavenger of *OH) or superoxide dismutase (a scavenger of O(2)(-)) and appeared to be specific to AII(t), since ONOO(-) only slightly influenced annexin I-mediated liposome aggregation. The conformational change of AII(t) induced by Ca(2+) had no effect on the inhibition. Furthermore, ONOO(-) only partially inhibited the binding of AII(t) to membranes. Nitration of AII(t) also occurred in intact A549 cells, a lung epithelial cell line, treated with ONOO(-). The results of this study suggest that AII(t)-mediated liposome aggregation was inhibited by nitration of the protein.
- Published
- 2002
12. Redox Reactions of the α-Synuclein-Cu2+ Complex and Their Effects on Neuronal Cell Viability.
- Author
-
Chengshan Wang, Lin Liu, Lin Zhang, Yong Peng, and Feimeng Zhou
- Subjects
- *
OXIDATION-reduction reaction , *NEUROLOGICAL disorders , *PARKINSON'S disease , *COPPER , *PEPTIDES , *NEUROBLASTOMA , *DOPAMINE - Abstract
α-Synuclein (α-syn), a presynaptic protein believed to play an important role in neuropathology in Parkinson's disease (PD), is known to bind Cu2+. Cu2+ has been shown to accelerate the aggregation of α-syn to form various toxic aggregates in vitro. Copper is also a redox-active metal whose complexes with amyloidogenic proteins/peptides have been linked to oxidative stress in major neurodegenerative diseases. In this work, the formation of the Cu2+ complex with α-syn or with an N-terminal peptide, α-syn(1-19), was confirmed with electrospray-mass spectrometry (ES-MS). The redox potentials of the Cu2+ complex with α-syn (α-syn-Cu2+) and α-syn(1-19) were determined to be 0.018 and 0.053 V, respectively. Furthermore, the Cu2+ center(s) can be readily reduced to Cu+, and possible reactions of α-syn-Cu2+ with cellular species (e.g., O2, ascorbic acid, and dopamine) were investigated. The occurrence of a redox reaction can be rationalized by comparing the redox potential of the α-syn-Cu2+ complex to that of the specific cellular species. For example, ascorbic acid can directly reduce α-syn-Cu2+ to α-syn-Cu+, setting up a redox cycle in which O2 is reduced to H2O2 and cellular redox species is continuously exhausted. In addition, the H2O2 generated was demonstrated to reduce viability of the neuroblastoma SY-HY5Y cells. Although our results ruled out the direct oxidation of dopamine by α-syn-Cu2+, the H2O2 generated in the presence of α-syn-Cu2+ can oxidize dopamine. Our results suggest that oxidative stress is at least partially responsible for the loss of dopaminergic cells in PD brain and reveal the multifaceted role of the α-syn-Cu2+ complex in oxidative stress associated with PD symptoms. [ABSTRACT FROM AUTHOR]
- Published
- 2010
- Full Text
- View/download PDF
13. Kinetics of Inhibition of β-Amyloid Aggregation by Transthyretin.
- Author
-
Lin Liu and Murphy, Regina M.
- Subjects
- *
AMYLOID , *CELL proliferation , *CANCER cells , *ALZHEIMER'S disease , *LABORATORY mice , *ANIMAL models in research , *BIOCHEMICAL genetics , *BIOCHEMISTRY - Abstract
Deposition of β-amyloid (Aβ) fibrils is an early event in the neurodegenerative processes associated with Alzheimer's disease. According to the ‘amyloid cascade’ hypothesis, Aβ aggregation, and its subsequent deposition as fibrils, is the underlying cause of disease. Aβ is a proteolytic product of amyloid precursor protein (APP); several mutations in APP have been identified that are associated with early onset of disease. Transgenic mice overexpressing APP with the Swedish mutation develop numerous plaques but, surprisingly, lack the neurofibrillary tangles and neuronal loss characteristic of Alzheimer's disease, in apparent contradiction of the amyloid cascade hypothesis. However, recent studies suggest that coproduction of sAPPα, an alternative proteolytic product of APP, increases synthesis of transthyretin that, in turn, interacts directly with Aβ to inhibit its toxicity. Here we report results from biophysical analysis of Aβ aggregation kinetics in the presence of transthryetin. At substoichiometric ratios, transthyretin drastically decreased the rate of aggregation without affecting the fraction of Aβ in the aggregate pool. Detailed analysis of the data using a mathematical model demonstrated that the decrease in aggregation rate was due to both a decrease in the rate of elongation relative to the rate of initiation of filaments and a decrease in lateral association of filaments to fibrils. Tryptophan quenching data indicated that transthyretin binds weakly to Aβ, with an estimated apparent Ks of 2300 M-1. Taken together, the data support a hypothesis wherein transthyretin preferentially binds to aggregated rather than monomeric Aβ and arrests further growth of the aggregates. [ABSTRACT FROM AUTHOR]
- Published
- 2006
- Full Text
- View/download PDF
14. Characterization of Protein Kinase C θ Activation Loop Autophosphorylation and the Kinase Domain Catalytic Mechanism.
- Author
-
Czerwinski, Robert, Aulabaugh, Ann, Greco, Rita M., Olland, Stephane, Malakian, Karl, Wolfrom, Scott, Lin, Laura, Kriz, Ron, Stahl, Mark, Ying Huang, Lin Liu, and Chaudhary, Divya
- Published
- 2005
- Full Text
- View/download PDF
15. Nitration of Annexin II Tetramer.
- Author
-
Rowan III, William H., Sun, Peng, and Lin Liu
- Published
- 2002
- Full Text
- View/download PDF
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