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Biomedical subjects

L Gu

Publications and source records attributed to L Gu.

At least 37 records · Page 2Linked to original sources
PubMed1999

Mismatch repair processing of carcinogen-DNA adducts triggers apoptosis.

The DNA mismatch repair pathway is well known for its role in correcting biosynthetic errors of DNA replication. We report here a novel role for mismatch repair in signaling programmed cell death in response to DNA damage induced by chemical carcinogens. Cells proficient in mismatch repair were highly sensitive to the cytotoxic effects of chemical carcinogens, while cells defective in either human MutS or MutL homologs were relatively insensitive. Since wild-type cells but not mutant cells underwent apoptosis upon treatment with chemical carcinogens, the apoptotic response is dependent on a functional mismatch repair system. By analyzing p53 expression in several pairs of cell lines, we found that the mismatch repair-dependent apoptotic response was mediated through both p53-dependent and p53-independent pathways. In vitro biochemical studies demonstrated that the human mismatch recognition proteins hMutSalpha and hMutSbeta efficiently recognized DNA damage induced by chemical carcinogens, suggesting a direct participation of mismatch repair proteins in mediating the apoptotic response. Taken together, these studies further elucidate the mechanism by which mismatch repair deficiency predisposes to cancer, i.e., the deficiency not only causes a failure to repair mismatches generated during DNA metabolism but also fails to direct damaged and mutation-prone cells to commit suicide.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
PubMed1999

Quantitative trait locus analysis of plasma lipoprotein levels in an autoimmune mouse model : interactions between lipoprotein metabolism, autoimmune disease, and atherogenesis.

The autoimmune MRL/lpr mouse strain, a model for systemic lupus erythematosus, exhibited an unusual plasma lipoprotein profile, suggesting a possible interaction of autoimmune disease and lipoprotein metabolism. In an effort to examine the genetic basis of such interactions, and to study their relationship to atherogenesis, we performed a quantitative trait locus analysis using a total of 272 (MRL/lprxBALB/cJ) second generation (F2) intercross mice. These mice were examined for levels of total plasma cholesterol, HDL cholesterol, VLDL and LDL cholesterol, unesterified cholesterol, autoantibodies, and aortic fatty streak lesions. Using a genome scan approach, we identified 4 quantitative trait loci controlling plasma lipoprotein levels on chromosomes (Chrs) 5, 8, 15, and 19. The locus on Chr 15 exhibited lod scores of 11.1 for total cholesterol and 6.7 for VLDL and LDL cholesterol in mice fed an atherogenic diet, and it contains a candidate gene, the sterol regulatory element binding protein-2. The locus on Chr 5 exhibited lod scores of 3.8 for total cholesterol and 4.1 for unesterified cholesterol in mice fed an atherogenic diet, and this locus has been observed in 2 previous studies. The locus on Chr 8 exhibited a lod score of 3.1 for unesterified cholesterol in mice fed a chow diet. This locus contains the lecithin-cholesterol acyltransferase gene, and decreased activity of the enzyme in the MRL strain suggests that this gene underlies the quantitative-trait locus. The locus on Chr 19 exhibited a lod score of 8.4 for HDL cholesterol and includes the Fas gene, which is mutated in MRL/lpr mice and is primarily responsible for the autoimmune phenotype in this cross. That the Fas gene is responsible for the HDL quantitative-trait loci is supported by the finding that autoantibody levels were strongly correlated with HDL cholesterol levels (rho=-0.37, P<0.0001) among the F2 mice. HDL cholesterol levels were in turn significantly associated with aortic fatty streak lesions among the F2 mice (rho=-0.17, P=0.006). Further, there was a threshold effect of autoantibody levels on the development of fatty streak lesions (rho=0.45, P=0.004 for 42 F2 mice with anti-dsDNA Ab over 0.5 OD). Our results support the concept that the high prevalence of coronary artery disease in systemic lupus erythematosus is due in part to a reduction of HDL cholesterol levels resulting from the autoimmune disease.

Animals↗
PubMed1999

MCP-1 deficiency reduces susceptibility to atherosclerosis in mice that overexpress human apolipoprotein B.

The earliest recognizable atherosclerotic lesions are fatty streaks composed of lipid-laden macrophages (foam cells). Circulating monocytes are the precursors of these foam cells, but the molecular mechanisms that govern macrophage trafficking through the vessel wall are poorly understood. Monocyte chemoattractant protein-1 (MCP-1), a member of the chemokine (chemotactic cytokine) family, is a potent monocyte agonist that is upregulated by oxidized lipids. Recent studies in hypercholesterolemic mice lacking apo E or the low-density lipoprotein receptor have suggested a role for MCP-1 in monocyte recruitment to early atherosclerotic lesions. To determine if MCP-1 is critically involved in atherogenesis in the setting of elevated physiological plasma cholesterol levels, we deleted the MCP-1 gene in transgenic mice expressing human apo B. Here we report that the absence of MCP-1 provides dramatic protection from macrophage recruitment and atherosclerotic lesion formation in apo B transgenic mice, without altering lipoprotein metabolism. Taken together with the results of earlier studies, these data provide compelling evidence that MCP-1 plays a critical role in the initiation of atherosclerosis.

Animals↗
PubMed1998

Genetic determinants of autoimmune disease and coronary vasculitis in the MRL-lpr/lpr mouse model of systemic lupus erythematosus.

MRL-lpr/lpr (MRL/lpr) mice are a model of human autoimmune disease. They exhibit a number of characteristics of systemic lupus erythematosus, including anti-DNA Abs, anti-cardiolipin Abs, immune complex-mediated vasculitis, lymphadenopathy, and severe glomerulonephritis. Although the autoimmune disorder is mediated primarily by mutation of the Fas gene (lpr), which interferes with lymphocyte apoptosis, MRL/lpr mice also have other predisposing genetic factors. In an effort to identify these additional factors, we have applied quantitative trait locus (QTL) mapping using an intercross between MRL/lpr mice and the nonautoimmune inbred strain BALB/cJ. A complete linkage map spanning the entire genome was constructed for 189 intercross progeny, and genetic loci contributing to features of the autoimmunity were identified using statistical analytic procedures. As expected, the primary genetic determinant of autoimmune disease in this cross was the Fas gene on mouse chromosome 19, exhibiting a lod score of 60. In addition, two novel loci, one on chromosome 2 (lod score, 4.3) and one on chromosome 11 (lod score, 3.1), were found to contribute to levels of anti-DNA Abs. Interestingly, the chromosome 19 and chromosome 11 QTLs, but not the chromosome 2 QTL, also exhibited associations with anti-cardiolipin Abs (lod scores, 38.4 and 2.6). We further examined the effects of these QTLs on the development of coronary vasculitis in the F2 mice. Our results indicate that the QTLs on chromosomes 11 and 19 also control the development of vasculitis, demonstrating common genetic determinants of autoantibody levels and vasculitis.

Animals↗
PubMed1998

Mice lacking serum paraoxonase are susceptible to organophosphate toxicity and atherosclerosis.

Serum paraoxonase (PON1) is an esterase that is associated with high-density lipoproteins (HDLs) in the plasma; it is involved in the detoxification of organophosphate insecticides such as parathion and chlorpyrifos. PON1 may also confer protection against coronary artery disease by destroying pro-inflammatory oxidized lipids present in oxidized low-density lipoproteins (LDLs). To study the role of PON1 in vivo, we created PON1-knockout mice by gene targeting. Compared with their wild-type littermates, PON1-deficient mice were extremely sensitive to the toxic effects of chlorpyrifos oxon, the activated form of chlorpyrifos, and were more sensitive to chlorpyrifos itself. HDLs isolated from PON1-deficient mice were unable to prevent LDL oxidation in a co-cultured cell model of the artery wall, and both HDLs and LDLs isolated from PON1-knockout mice were more susceptible to oxidation by co-cultured cells than the lipoproteins from wild-type littermates. When fed on a high-fat, high-cholesterol diet, PON1-null mice were more susceptible to atherosclerosis than their wild-type littermates.

Animals↗
PubMed1998

ZO-3, a novel member of the MAGUK protein family found at the tight junction, interacts with ZO-1 and occludin.

A 130-kD protein that coimmunoprecipitates with the tight junction protein ZO-1 was bulk purified from Madin-Darby canine kidney (MDCK) cells and subjected to partial endopeptidase digestion and amino acid sequencing. A resulting 19-amino acid sequence provided the basis for screening canine cDNA libraries. Five overlapping clones contained a single open reading frame of 2,694 bp coding for a protein of 898 amino acids with a predicted molecular mass of 98,414 daltons. Sequence analysis showed that this protein contains three PSD-95/SAP90, discs-large, ZO-1 (PDZ) domains, a src homology (SH3) domain, and a region similar to guanylate kinase, making it homologous to ZO-1, ZO-2, the discs large tumor suppressor gene product of Drosophila, and other members of the MAGUK family of proteins. Like ZO-1 and ZO-2, the novel protein contains a COOH-terminal acidic domain and a basic region between the first and second PDZ domains. Unlike ZO-1 and ZO-2, this protein displays a proline-rich region between PDZ2 and PDZ3 and apparently contains no alternatively spliced domain. MDCK cells stably transfected with an epitope-tagged construct expressed the exogenous polypeptide at an apparent molecular mass of approximately 130 kD. Moreover, this protein colocalized with ZO-1 at tight junctions by immunofluorescence and immunoelectron microscopy. In vitro affinity analyses demonstrated that recombinant 130-kD protein directly interacts with ZO-1 and the cytoplasmic domain of occludin, but not with ZO-2. We propose that this protein be named ZO-3.

Amino Acid Sequence↗
PubMed1998

ATP-dependent interaction of human mismatch repair proteins and dual role of PCNA in mismatch repair.

DNA mismatch repair ensures genomic stability by correcting biosynthetic errors and by blocking homologous recombination. MutS-like and MutL-like proteins play important roles in these processes. In Escherichia coli and yeast these two types of proteins form a repair initiation complex that binds to mismatched DNA. However, whether human MutS and MutL homologs interact to form a complex has not been elucidated. Using immunoprecipitation and Western blot analysis we show here that human MSH2, MLH1, PMS2 and proliferating cell nuclear antigen (PCNA) can be co-immunoprecipitated, suggesting formation of a repair initiation complex among these proteins. Formation of the initiation complex is dependent on ATP hydrolysis and at least functional MSH2 and MLH1 proteins, because the complex could not be detected in tumor cells that produce truncated MLH1 or MSH2 protein. We also demonstrate that PCNA is required in human mismatch repair not only at the step of repair initiation, but also at the step of repair DNA re-synthesis.

Adaptor Proteins, Signal Transducing↗
PubMed1998

Abnormalities in monocyte recruitment and cytokine expression in monocyte chemoattractant protein 1-deficient mice.

Monocyte chemoattractant protein 1 (MCP-1) is a CC chemokine that attracts monocytes, memory T lymphocytes, and natural killer cells. Because other chemokines have similar target cell specificities and because CCR2, a cloned MCP-1 receptor, binds other ligands, it has been uncertain whether MCP-1 plays a unique role in recruiting mononuclear cells in vivo. To address this question, we disrupted SCYA2 (the gene encoding MCP-1) and tested MCP-1-deficient mice in models of inflammation. Despite normal numbers of circulating leukocytes and resident macrophages, MCP-1(-/-) mice were specifically unable to recruit monocytes 72 h after intraperitoneal thioglycollate administration. Similarly, accumulation of F4/80+ monocytes in delayed-type hypersensitivity lesions was impaired, although the swelling response was normal. Development of secondary pulmonary granulomata in response to Schistosoma mansoni eggs was blunted in MCP-1(-/-) mice, as was expression of IL-4, IL-5, and interferon gamma in splenocytes. In contrast, MCP-1(-/-) mice were indistinguishable from wild-type mice in their ability to clear Mycobacterium tuberculosis. Our data indicate that MCP-1 is uniquely essential for monocyte recruitment in several inflammatory models in vivo and influences expression of cytokines related to T helper responses.

Animals↗
PubMed1998

Characterization of N-(Nitrosomethyl)urea in Nitrosated Fermented Fish Products.

To characterize chemical carcinogens in acidic-nitrosated fish sauce sample, N-nitrosamides in the sample were separated by two kinds of reversed-phase HPLC columns, and with detection by photolysis-pyrolysis-thermal energy analyzer. A strong chromatographic peak at t(R) 12 or 4.5 min, same as that for N-(nitrosomethyl)urea (NMU), was obtained on PRP-1 or C(18) HPLC column from fish sauce sample with 10 mM trifluoroacetic acid as the basic mobile; acetonitrile, as organic modifier after the sample was nitrosated by 5 mmol/L of sodium nitrite (final concentration) at 37 degrees C and pH 2.0 for 1 h. No response above t(R) could be observed from the nitrosated sample in the detection system without photolysis. Such a peak could not be obtained from the unnitrosated fish sauce either. These results indicated that the component was NMU. Furthermore, this component, NMU, could also be detected in the nitrosated human gastric juice sample spiked with fish sauce. The formation of NMU in the sample was pH- and nitrite-dependent. This paper provides direct evidence that NMU formation could occur in fish sauce from the high-risk area for stomach cancer and in the fish sauce spiked human gastric juice during nitrosation under simulated gastric conditions.

Journal Article↗
PubMed1998

Metabolic fate of glucose in vascular smooth muscle during contraction induced by norepinephrine.

The metabolism of glucose in porcine carotid artery was tracked by isotopic methods during sustained isometric contraction induced by 100 microM norepinephrine (NE). In resting muscles, 74 and 18% of glucose taken up was accounted for by glycolysis and glycogen synthesis, respectively. Lactate production accounted for 69%, pyruvate production for 12%, and glucose oxidation accounted for 14% of glycolytic flux. The oxidation of glucose accounted for 57% of the consumption of O2 and thus constituted the primary oxidative substrate. During contraction by NE, glucose-uptake declined modestly below the resting basal rate. Glycolysis of external glucose and lactate production decreased and then increased with sustained contraction. Norepinephrine stimulated simultaneous glycogenolysis and glycogen synthesis, with net glycogen synthesis prevailing over 90 min of isometric contraction. Furthermore, NE modified the distribution of glucosyl units throughout the glycogen pool. The steady state rate of oxidation of glucose did not increase during NE contraction, even though O2-consumption increased. In contrast, increased glucose oxidation was demonstrable during contraction induced by 80 mm KCl. Furthermore, oxidation of exogenous fatty acid could be demonstrated during NE-induced contraction. Thus, NE exerts multiple effects on glucose and glycogen metabolism in smooth muscle, but it does not stimulate glucose oxidation.

Animals↗
PubMed1998

Malate-aspartate shuttle, cytoplasmic NADH redox potential, and energetics in vascular smooth muscle.

The effect of inhibition of the malate-aspartate shuttle on the cytoplasmic NADH/NAD ratio and NADH redox state and its corresponding effects on mitochondrial energetics in vascular smooth muscle were examined. Incubation of porcine carotid arteries with 0. 4 mmol amino-oxyacetic acid an inhibitor of glutamate-oxaloacetate transaminase and, hence the malate-aspartate shuttle, inhibited O2 consumption by 21%, decreased the content of phosphocreatine and inhibited activity of the tricarboxylic acid cycle. The rate of glycolysis and lactate production was increased but glucose oxidation was inhibited. These effects of amino-oxyacetic acid were accompanied by evidence of inhibition of the malate-aspartate shuttle and elevation in the cytoplasmic redox potential and NADH/NAD ratio as indicated by elevation of the concentration ratios of the lactate/pyruvate and glycerol-3-phosphate/dihydroxyacetone phosphate metabolite redox couples. Addition of the fatty acid octanoate normalized the adverse energetic effects of malate-aspartate shuttle inhibition. It is concluded that the malate-aspartate shuttle is a primary mode of clearance of NADH reducing equivalents from the cytoplasm in vascular smooth muscle. Glucose oxidation and lactate production are influenced by the activity of the shuttle. The results support the hypothesis that an increased cytoplasmic NADH redox potential impairs mitochondrial energy metabolism.

Aminooxyacetic Acid↗
PubMed1998

Electromechanical coupling model of gating the large mechanosensitive ion channel (MscL) of Escherichia coli by mechanical force.

We have developed a theoretical electromechanical coupling (EMC) model of gating of the large-conductance mechanosensitive ion channel (MscL). The model presents the first attempt to explain the pressure-dependent transitions between the closed and open channel conformations on a molecular level by assuming 1) a homohexameric structural model of the channel, 2) electrostatic interactions between various domains of the homohexamer, 3) structural flexibility of the N-terminal portion of the monomer, and 4) mechanically and electrostatically induced displacement of the N-terminal domain relative to other structural domains of the protein. In the EMC model, 12 membrane-spanning alpha-helices (six each of the M1 and M2 transmembrane domains of the MscL monomer), are envisaged to line the channel pore with a diameter of 40 A, whereas the N- and C-termini are oriented toward each other inside the pore when the channel is closed. The model proposes that stretching the membrane bilayer by mechanical force causes the monomers to be pulled away from and slightly tilted toward each other. This relative movement of alpha-helices could serve as a trigger to initiate a "swing-like" motion of the N-terminus around the glycine residue G14 that may act as a pivot. The analysis of the attractive and repulsive coulomb forces between all domains of the channel homohexamer suggested that an inclination angle of approximately 3.0 degrees - 4.1 degrees between the oppositely oriented channel monomers should suffice for the N-terminus to turn away from other domains causing the channel to open. According to the EMC model the minimal free energy change, deltaG, that could initiate the opening of the channel was 2 kT. Also, the model predicted that the negative pressure required for channel open probability, Po = 0.5, should be between 50 and 80 mmHg. These values were in a good agreement with the experimentally estimated pressures of 60-70 mmHg obtained with the MscL reconstituted in liposomes. Furthermore, consistent with a notion that the N-terminus may present a mechanosensitive structural element providing a mechanism to open the MscL by mechanical force, the model provides a simple explanation for the variations in pressure sensitivity observed with several MscL mutants having either deletions or substitutions in N- or C-terminus, or site-directed mutations in the S2-S3 loop.

Amino Acid Sequence↗
PubMed1998

Absence of monocyte chemoattractant protein-1 reduces atherosclerosis in low density lipoprotein receptor-deficient mice.

Recruitment of blood monocytes into the arterial subendothelium is one of the earliest steps in atherogenesis. Monocyte chemoattractant protein-1 (MCP-1), a CC chemokine, is one likely signal involved in this process. To test MCP-1's role in atherogenesis, low density lipoprotein (LDL) receptor-deficient mice were made genetically deficient for MCP-1 and fed a high cholesterol diet. Despite having the same amount of total and fractionated serum cholesterol as LDL receptor-deficient mice with wild-type MCP-1 alleles, LDL receptor/MCP-1-deficient mice had 83% less lipid deposition throughout their aortas. Consistent with MCP-1 's monocyte chemoattractant properties, compound-deficient mice also had fewer macrophages in their aortic walls. Thus, MCP-1 plays a unique and crucial role in the initiation of atherosclerosis and may provide a new therapeutic target in this disorder.

Animals↗
PubMed1998

Pediatric acute myelogenous leukemia cells express IL-6 receptors and are sensitive to a recombinant IL6-Pseudomonas exotoxin.

We have studied IL-6 receptor (IL-6R) expression on AML cells from 15 pediatric patients by immunocytochemistry/flow cytometry, reverse-transcription polymerase chain reaction, and Scatchard analysis. High-affinity IL-6R were detected on leukemic cells from 12 (80%) patients. Binding sites per cell ranged from 140 to 3580 (median 920; mean 1240), with dissociation constants of 0.26 to 0.71 nM. We therefore assessed the in vitro sensitivity of IL-6R+ AML cells to treatment with a recombinant IL6-Pseudomonas exotoxin fusion protein (IL6-PE4E), using the XTT cytotoxicity assay. Leukemic cells from eight patients had ID50 values (concentration of IL6-PE4E producing a 50% decrease in cell viability) of <1000 ng/ml (median, 87 ng/ml; mean, 262 ng/ml). Sensitivity to IL6-PE4E correlated significantly with receptor number. Normal bone marrow mononuclear cells had undetectable IL6-R expression (<20 receptors/cell) and were relatively resistant to IL6-PE4E. To test the efficacy of IL6-PE4E for ex vivo purging in an autologous stem cell transplantation setting, we incubated primary IL-6R+ AML cells with 10(3) ng/ml IL6-PE4E for 24 h, followed by inoculation into SCID mice. Mice receiving treated cells showed no leukemic engraftment, while all mice receiving untreated or control-treated cells developed leukemia with a median presymptomatic interval of 55 days. In recipients of IL6-PE4E treated cells, no evidence of occult leukemia was detected by PCR analysis of blood and bone marrow cells at 185 days postinoculation. These data suggest that IL-6R are expressed on leukemic cells from a substantial percentage of pediatric AML patients. Furthermore, leukemic cells expressing high numbers of IL6-R may be sensitive to IL6-PE4E in an ex vivo purging protocol.

ADP Ribose Transferases↗
PubMed1998

Sensitivity to Fas-mediated apoptosis in pediatric acute lymphoblastic leukemia is associated with a mutant p53 phenotype and absence of Bcl-2 expression.

Fas (APO-1/CD95) is a cell-surface protein that can mediate apoptosis upon specific ligand or antibody binding. The Bcl-2 protein may function as a modulator of Fas-induced apoptosis by blocking a downstream activation step, and Bcl-2 expression in acute lymphoblastic leukemia (ALL) cells appears to depend partly on expression of a wild-type (wt) p53 tumor suppressor gene (Findley et al, Blood 1997; 89: 2986). We therefore investigated the relationship between sensitivity to Fas-mediated apoptosis and (1) Fas expression, (2) p53 status, and (3) Bcl-2 protein levels in pediatric ALL cell lines and primary leukemic cells. Cell lines included 21 B cell precursor (BCP)-ALL and four T-ALL lines; in five cases, cryopreserved primary leukemic cells from which these lines were established were also examined. Additionally, we evaluated the effect of anti-Fas monoclonal antibody on the activation of protease CPP32 and induction of apoptosis in these lines. By SSCP analysis and DNA sequencing, we detected p53 mutations (mt) in eight out of 25 ALL cell lines (exon-7, codon 248 n=6; exon-8, codon 273, n=2). The expression of Fas and Bcl-2 was examined by immunofluorescence staining and quantified as the number of molecules of equivalent soluble fluorochrome (MESF). Elevated levels of Fas were expressed in all six lines with a mutation of p53 in codon 248 (1500 to 10800 MESF). Although Fas was detectable in seven of the 17 lines with wt-p53, expression was lower (150-900 MESF) compared with mt-p53+ lines. Bcl-2 was expressed in 10 of the 25 lines. Most (9/10) wt-p53+ lines expressed Bcl-2, whereas only one of eight mt-p53+ lines and no p53-null lines expressed this protein. Treatment of Fas-positive lines with anti-Fas monoclonal antibody (200 ng/ml) for 6 h induced activation of CPP32 and apoptosis in eight of 13 Fas+ lines. Sensitivity to Fas-mediated apoptosis was associated with a mt-p53 phenotype and absence of Bcl-2 expression. Six of eight Fas+/Fas-sensitive (S) lines were mt-53+/Bcl-2-, whereas only two Fas+/Fas-S lines were wt-p53+/Bcl-2+; both of these latter lines expressed low levels of Bcl-2 compared to Fas-resistant lines. In contrast, four of five Fas+/Fas-resistant (R) lines were wt-p53+/Bcl-2+; the exception was p53-null/Bcl-2- but expressed a low level of Fas (150 MESF). Activation of the cysteine protease CPP32 and cleavage of its substrate poly(ADP-ribose)polymerase (PARP) was also detected in Fas-S but not Fas-R lines. We obtained similar results from both the primary leukemic cells and the corresponding cell lines in five cases: overexpression of Fas and Fas-sensitivity were present in mt-p53+/Bcl-2- but not wt-p53+/Bcl-2+ cells. These results suggest that some pediatric ALL cells expressing mt-p53+ may be sensitive to Fas-mediated apoptosis due to high levels of Fas expression and lack of Bcl-2, and further suggest that molecular methods of activating Fas may be useful for therapy of refractory ALL with the Fas+/mt-p53+ phenotype.

Apoptosis↗
PubMed1998

Differential roles of GATA-1 and GATA-2 in growth and differentiation of mast cells.

BACKGROUND: While mast cells have been previously shown to express both GATA-1 and GATA-2 mRNAs, individual functions for these related factors during their course of differentiation within the mast cell lineage have not yet been defined. To address this question, the expression of GATA-1 and GATA-2 mRNAs and proteins were examined in three mouse mast cell progenitor lines as well as in mast cells isolated from both wild-type and GATA-1-deficient mice. RESULTS: Both mast cell progenitor lines, as well as primary mouse bone marrow-derived mast cells (BMMCs) and peritoneal mast cells (PMCs) were examined by RNA blotting and immunological analyses. GATA-2 protein was abundantly expressed in all three mast cell lines and in BMMCs, but only weakly in some of PMCs. In contrast, GATA-1 protein was expressed in PMCs and BMMCs after culture in the presence of IL3 and SCF. We also found the presence of Alcian blue staining-positive but berberine staining-negative mast cells in the skin of mice heterozygous to GATA-1 knock-down allele. CONCLUSION: These results suggest that the expression of GATA factor-dependent genes is regulated by GATA-2 during mast cell development and that GATA-1 is required for the specification of differentiated mast cell phenotypes.

Animals↗
PubMed1998

[Protein status and antioxidant capability of residents in endemic and nonendemic areas of Keshan disease(KD)].

From a survey of residents in endemic and nonendemic areas of Keshan disease(KD), it was found that the plasma cystine, tryptophan and lysine as well as blood selenium content were lower, while the plasma lipid peroxide was higher in endemic areas than those in non-endemic areas. These results suggests that the selenium deficiency coexisting with cystine and tryptophan insufficiency decreases the antioxidant defense of the organism and may be one of the important factors for the development of KD. The role of sulfur-containing amino acid in antioxidant defense is discussed emphatically.

Adult↗