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Peng Wang

Publications and source records attributed to Peng Wang.

At least 127 records · Page 7Linked to original sources
PubMed2004

Liquid chromatography-mass spectrometry method for determination of tetramethylpyrazine and its metabolite in dog plasma.

A liquid chromatography-mass spectrometry method is described for the determination of tetramethylpyrazine (TMP) and its active metabolite, 2-hydroxymethyl-3,5,6-trimethylpyrazine (HTMP) in dog plasma. This method involves a plasma clean-up step using protein precipitation procedure followed by LC separation and positive electrospray ionization mass spectrometry detection (ESI-MS). Chromatographic separation of the analytes was achieved on a C18 column using a mobile phase of methanol, water and acetic acid (50:50:0.6, v/v/v) at a flow rate of 1.0 ml/min. Selected ion monitoring (SIM) mode was used for analyte quantitation at m/z 137.2 for TMP, m/z 153.2 for HTMP and m/z 195.2 for caffeine. The linearity was obtained over the concentration ranges of 20-6000 ng/ml for TMP and 20-4000 ng/ml for HTMP and the lower limit of quantitation was 20 ng/ml for both analytes. For each level of QC samples, both inter- and intra-day precisions (R.S.D.) were <or=7.4% for TMP and <or=6.0% for HTMP, and accuracy (R.E.) was +/-6.0% for TMP and <or=3.5% for HTMP. The proposed LC-MS method was successfully applied to the pharmacokinetic studies of a TMP formulation preparation after oral administration to beagle dogs.

Animals↗
PubMed2004

Per-Arnt-Sim domain-dependent association of cAMP-phosphodiesterase 8A1 with IkappaB proteins.

Phosphodiesterase (PDE) 8A1 is a cAMP-specific PDE isozyme characterized by the presence of a Per-Arnt-Sim (PAS) domain. However, the function(s) of the PAS domain has remained unknown. In this study, using a lysate of HEK293 cells overexpressing recombinant human PDE8A1, we detected a physical association between PDE8A1 and endogenous IkappaBbeta by an antibody array technique. The association was specific for PDE8A1 and depended on the presence of the PAS domain. Subsequent coimmunoprecipitation experiments revealed that, in addition to IkappaBbeta, other IkappaB family members examined (p105, p100, and IkappaBalpha) also associated with PDE8A1. Furthermore, it was found that PDE8A1 competed with the p65/p50 NF-kappaB for IkappaBbeta binding. Taken together, these data indicate that PDE8A1, through its PAS domain, may bind with IkappaB proteins in a region containing their ankyrin repeats. Functionally, in vitro and in vivo experiments demonstrated that the association with IkappaB greatly enhanced the enzyme activity of PDE8A1. However, the PDE8A1-IkappaB association did not affect NF-kappaB activation. The biological role of the PDE8A1-IkappaB association remains to be elucidated.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed2004

Differential type 4 cAMP-specific phosphodiesterase (PDE4) expression and functional sensitivity to PDE4 inhibitors among rats, monkeys and humans.

It has been suggested that the rat is relatively more susceptible to toxicity induced by inhibitors for type 4 cAMP-specific phosphodiesterase (PDE4). In this study designed to elucidate possible biochemical basis for the higher susceptibility, we compared PDE4 expression levels and their functional relevance among rats, monkeys and humans. In several toxicologically relevant tissues and blood leukocytes, the mRNA expression levels of PDEs 4A, 4B, 4C and 4D were significantly higher in rats than in humans. We confirmed that higher PDE4 expression levels were correlated with a higher enzyme activity level in rat leukocytes. The PDE4 enzyme activity level of leukocytes in monkeys fell between that of rats and humans. Functionally, the potencies of the PDE4 inhibitors rolipram, SB 207499 and SCH 351591 in inhibiting tumor necrosis factor production from leukocytes were in the following order: rat > monkey > human. In addition, rolipram was about 10-fold more potent in rats than in humans in inhibiting phenylephrine-induced contraction of renal artery. These inhibitors were confirmed to be highly selective for PDE4 in comparison to all other PDE families, and to inhibit rat and human PDE4s with identical potencies. Taken together, these results suggest that the higher susceptibility of rats to PDE4 inhibitor-induced toxicity might be due to their higher expression levels of PDE4, and that PDE4 inhibitors may be safer in humans than in monkeys and, particularly, rats.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed2004

Methylation profile of the promoter CpG islands of 14 "drug-resistance" genes in hepatocellular carcinoma.

AIM: To establish the DNA methylation patterns of the promoter CpG islands of 14 "drug-resistance" genes in hepatocellular carcinoma (HCC). METHODS: The methylation specific polymerase chain reaction in conjunction with sequencing verification was used to establish the methylation patterns of the 14 genes in the liver tissues of four healthy liver donors, as well as tumor and the paired non-cancerous tissues of 30 HCC patients. RESULTS: While 11 genes (ATP-binding cassette, sub-family G (WHITE), member 2(ABCG2), activating transcription factor (ATF2), beta-2-microglobulin (B2M), deoxycytidine kinase (DCK), occludin (OCLN), v-raf-1 murine leukemia viral oncogene homolog (RAF1), ralA binding protein 1 (RALBP1), splicing factor (45 kD) (SPF45), S-phase kinase-associated protein 2 (p45) (SKP2), tumor protein p53 (Li-Fraumeni syndrome) (TP53) and topoisomerase (DNA) II beta (TOP2B)) maintained the unmethylated patterns, three genes displayed to various extents the hypermethylation state in tumor tissues in comparison with the normal counterparts. The catalase (CAT) was hypermethylated in tumor and the neighboring non-cancerous tissue of one case (3.3%). Both glutathione S-transferase pi (GSTpi) (80%, 24/30 in tumor and 56.7%, 17/30 in the paired non-cancerous tissues) and cystic fibrosis transmembrane conductance regulator, ATP-binding cassette (sub-family C, member 7) (CFTR) (77%, 23/30 in tumor and 50%, 15/30 in the paired non-cancerous tissues) genes were prevalently hypermethylated in HCC as well as their neighboring non-cancerous tissues. No significant difference in the hypermethylation occurrence was observed between the HCC and its neighboring non-cancerous tissues. CONCLUSION: Hypermethylation of promoter CpG islands of both CFTR and GSTpi genes occurs prevalently in HCC, which may correlate with the low expression of these two genes at the mRNA level and has the profound etiological and clinical implications. It is likely to be specific to the early phase of HCC carcinogenesis.

Acyltransferases↗
PubMed2004

Methylation profile of the promoter CpG islands of 31 genes that may contribute to colorectal carcinogenesis.

AIM: To establish the methylation profile of the promoter CpG islands of 31 genes that might play etiological roles in colon carcinogenesis. METHODS: The methylation specific PCR in conjunction of sequencing verification was used to establish the methylation-profile of the promoter CpG islands of 31 genes in colorectal cancer (n = 65), the neighboring non-cancerous tissues (n = 5), colorectal adenoma (n = 8), and normal mucosa (n = 1). Immunohistochemically, expression of 10 genes was assessed on the home-made tissue microarrays of tissues from 58 patients. The correlation of tumor specific changes with each of clinical-pathologic features was scrutinized with relevant statistic tools. RESULTS: In comparison with the normal mucosa of the non-cancer patients, the following 14 genes displayed no tumor associated changes: breast cancer 1, early onset (BRCA1), cadherin 1, type 1, E-cadherin (epithelial) (CDH1), death-associated protein kinase 1 (DAPK1), DNA (cytosine-5-)-methyltransferase 1 (DNMT1), melanoma antigen, family A, 1 (directs expression of antigen MZ2-E) (MAGEA1), tumor suppressor candidate 3 (N33), cyclin-dependent kinase inhibitor 1A (p21, Cip1) (p21(WAF1)), cyclin-dependent kinase inhibitor 1B (p27, Kip1) (p27(KIP1)), phosphatase and tensin homolog (mutated in multiple advanced cancers 1) (PTEN), retinoic acid receptor, beta (RAR- , Ras association (RalGDS/AF-6) domain family 1 C (RASSF1C), secreted frizzled-related protein 1 (SFRP1), tissue inhibitor of metalloproteinase 3 (Sorsby fundus dystrophy, pseudoinflammatory) (TIMP3), and von Hippel-Lindau syndrome (VHL). The rest 17 targets exhibited to various extents the tumor associated changes. As changes in methylation of the following genes occurred marginally, their impact on the formation of colorectal cancer were trivial: adenomatous polyposis coli (APC) (8%, 5/65), Ras association (RalGDS/AF-6) domain family 1A (RASSF1A) (3%, 2/65) and cyclin-dependent kinase inhibitor 2A, alternated reading frame (p14(ARF)) (6%, 4/65). The following genes exhibited moderate changes in methylation: O-6-methylguanine-DNA methyltransferase (MGMT) (20%, 13/65), mutL homolog 1, colon cancer, nonpolyposis type 2 (E. coli) (hMLH1) (18%, 12/65), cyclin-dependent kinase inhibitor 2A (melanoma, p16, inhibits CDK4) (p16(INK4a)) (10%, 10/65), methylated in tumor 1 (MINT1) (15%, 10/65), methylated in tumor 31 (MINT31) (11%, 7/65). The rest changed greatly in the methylation pattern in colorectal cancer (CRC): cyclin A1 (cyclin a1) (100%, 65/65), caudal type homeobox transcription factor 1 (CDX1) (100%, 65/65), RAR- (85%, 55/65), myogenic factor 3 (MYOD1) (69%, 45/65), cyclin-dependent kinase inhibitor 2B (p15, inhibits CDK4) (p15(INK4b)) (68%, 44/65), prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) (COX2) (72%, 47/65), cadherin 13, H-cadherin (heart) (CDH13) (65%, 42/65), CAAX box 1 (CXX1) (58%, 38/65), tumor protein p73 (p73) (63%, 41/65) and Wilms tumor 1 (WT1) (58%, 38/65). However, no significant correlation of changes in methylation with any given clinical-pathological features was detected. Furthermore, the frequent changes in methylation appeared to be an early phase event of colon carcinogenesis. The in situ expression of 10 genes was assessed by the immunohistochemical approach at the protein level: CDH1, CDH13, COX2, cyclin A1, hMLH1, MGMT, p14(ARF), p73, RAR- , and TIMP3 genes in the context of the methylation status in colorectal cancer. No clear correlation between the hypermethylation of the promoter CpG islands and the negative expression of the genes was established. CONCLUSION: The methylation profile of 31 genes was established in patients with colon cancer and colorectal adenomas, which provides new insights into the DNA methylation mediated mechanisms underlying the carcinogenesis of colorectal cancer and may be of prognostic values for colorectal cancer.

ADP-Ribosylation Factor 6↗
PubMed2004

Loss of one allele of ARF rescues Mdm2 haploinsufficiency effects on apoptosis and lymphoma development.

The tumor suppressor p19ARF inhibits Mdm2, which restricts the activity of p53. Complicated feedback and control mechanisms regulate ARF, Mdm2, and p53 interactions. Here we report that ARF haploinsufficiency completely rescued the p53-dependent effects of Mdm2 haploinsufficiency on B-cell development, survival, and transformation. In contrast to Mdm2+/- B cells, Mdm2+/- B cells deficient in ARF were similar to wild-type B cells in their rates of growth and apoptosis and activation of p53. Consequently, the profoundly reduced numbers of B cells in Mdm2+/-Emu-myc transgenic mice were restored to normal levels in ARF+/-Mdm2+/-Emu-myc transgenics. Additionally, ARF+/-Mdm2+/-Emu-myc transgenics developed lymphomas at rates analogous to those observed for wild-type Emu-myc transgenics, demonstrating that loss of one allele of ARF rescued the protracted lymphoma latency in Mdm2+/-Emu-myc transgenics. Importantly, in ARF+/-Mdm2+/-Emu-myc transgenic lymphomas, p53 was inactivated at the frequency observed in lymphomas of wild-type Emu-myc transgenics. Collectively, these results support a model whereby the stoichiometry of Mdm2 and ARF controls apoptosis and tumor development, which should have significant implications in the treatment of malignancies that have inactivated ARF.

ADP-Ribosylation Factor 1↗
PubMed2004

A liquid chromatographic method for simultaneous determination of amoxicillin sodium and sulbactam sodium in a combination formulation.

An isocratic liquid chromatographic method with UV detection at 210nm is described for simultaneous determination of amoxicillin sodium and sulbactam sodium in a new combination formulation. Chromatographic separation of the two drugs was achieved on a Hypersil C(18) column using a mobile phase consisting of a binary mixture of methanol and 0.01mol/l sodium acetate (5:95, v/v). The commonly used paired-ion aqueous mobile phase for the determination of penicillins was avoided in this study. The developed LC method offers symmetric peak shape, good resolution and reasonable retention time for both drugs. Linearity, accuracy and precision were found to be acceptable over the concentration ranges of 155.3-1553.0microg/ml for amoxicillin sodium and 45.0-450.0microg/ml for sulbactam sodium. The proposed LC method can be used for the quality control of formulated products containing these two drugs.

Amoxicillin↗
PubMed2004

Cloning and functional analysis of a cDNA encoding Ginkgo biloba farnesyl diphosphate synthase.

Farnesyl diphosphate synthase (FPS; EC2.5.1.1/EC2. 5.1.10) catalyzes the synthesis of farnesyl diphosphate, and provides precursor for biosynthesis of sesquiterpene and isoprenoids containing more than 15 isoprene units in Ginkgo biloba. Here we report the cloning, characterization and functional analysis of a new cDNA encoding FPS from G. biloba. The full-length cDNA (designated GbFPS) had 1731 bp with an open reading frame of 1170 bp encoding a polypeptide of 390 amino acids. The deduced GbFPS was similar to other known FPSs and contained all the conserved regions of trans-prenyl chain-elongating enzymes. Structural modeling showed that GbFPS had the typical structure of FPS, the most prominent feature of which is the arrangement of 13 core helices around a large central cavity. Southern blot analysis revealed a small FPS gene family in G. biloba. Expression analysis indicated that GbFPS expression was high in roots and leaves, and low in stems. Functional complementation of GbFPS in an FPS-deficient strain confirmed that GbFPS mediates farnesyl diphosphate biosynthesis.

Alkyl and Aryl Transferases↗
PubMed2004

Overexpression of 5-lipoxygenase in rat and human esophageal adenocarcinoma and inhibitory effects of zileuton and celecoxib on carcinogenesis.

PURPOSE: Aberrant arachidonic acid (AA) metabolism, especially through the cyclooxygenase (Cox) and 5-lipoxygenase (5-Lox) pathways, has been suggested to play an important role in the development of esophageal adenocarcinoma (EAC). The purpose of this study was to investigate the expression of 5-Lox in EAC of a rat model and in human samples as well as the chemopreventive effects of zileuton (a specific 5-Lox inhibitor) and celecoxib (a specific Cox2 inhibitor) in the rat EAC model. EXPERIMENTAL DESIGN: 5-Lox expression in EAC of a rat esophagogastroduodenal anastomosis model and of humans was examined with immunohistochemistry. A chemoprevention study was designed to test whether zileuton and celecoxib could suppress aberrant AA metabolism and esophageal adenocarcinogenesis. RESULTS: With immunohistochemistry, we found that 5-Lox was overexpressed during esophageal adenocarcinogenesis in our rat model and in humans. In the chemoprevention study, EAC incidence was reduced in a dose-dependent manner from 68.8% (11 of 16) to 44.4% (8 of 18; P > 0.05) and 31.3% (5 of 16; P < 0.05) by 500 and 1,000 ppm zileuton, respectively, and to 33.3% (7 of 21; P < 0.05) and 20% (3 of 15; P < 0.05) by 500 and 1,000 ppm celecoxib, respectively. With isobolographic analysis, zileuton and celecoxib, both at a dose of 500 ppm, had an additive effect by reducing the tumor incidence to 16.7% (3 of 18, P < 0.01). Leukotriene B4 and prostaglandin E2 levels in the esophageal tissues were also significantly reduced by zileuton and celecoxib. CONCLUSIONS: This study clearly demonstrated that 5-Lox and Cox2 play important roles in the development of EAC. Both zileuton and celecoxib had inhibitory effects on esophageal adenocarcinogenesis through inhibition on their respective enzymes of AA metabolism.

Adenocarcinoma↗
PubMed2004

Simultaneous determination of roxithromycin and ambroxol hydrochloride in a new tablet formulation by liquid chromatography.

A rapid and accurate liquid chromatographic method is described for the simultaneous determination of roxithromycin and ambroxol hydrochloride in a new tablet formulation. Chromatographic separation of the two drugs was achieved on a Diamonsil C(18) column (200 mm x 4.6 mm, 5 microm). The mobile phase consisting of a mixture of acetonitrile, methanol and 0.5% ammonium acetate (39:11:50 (v/v), pH 5.5) was delivered at a flow rate of 1.0 ml/min. Detection was performed at 220 nm. Linearity, accuracy and precision were found to be acceptable over the concentration range of 201.2-2012.0 microg/ml for roxithromycin and 42.7-427.0 microg/ml for ambroxol hydrochloride, respectively. Separation was complete in less than 10 min. The proposed method can be used for the quality control of formulation products.

Ambroxol↗
PubMed2004

Differential inhibitor sensitivity between human recombinant and native photoreceptor cGMP-phosphodiesterases (PDE6s).

Human photoreceptor cGMP-phosphodiesterases (PDE6s) are important reagents in PDE inhibitor discovery. However, recombinant human PDE6s have not been expressed, and isolation of native human PDE6s is highly difficult. In this study, the catalytic subunit(s) of human rod and cone PDE6s (PDE6alphabeta and PDE6alpha', respectively) were co-expressed or expressed separately as catalytically active enzymes. Sildenafil inhibited both the recombinant PDE6s in a dose-dependent manner with Ki values of 94 and 98 nM, respectively. These Ki values were four-fold higher than that (25 nM) of a human native PDE6 preparation. Similarly, 3-isobutyl-1-methylxanthine (IBMX)'s Ki values for the recombinant PDE6s were five- to eight-fold higher than that of the native enzyme. However, E4021 and zaprinast exhibited much (30-80-fold) lower potencies for the recombinant PDE6s than for the native enzyme. Additional PDE5 inhibitors representing other structural classes and possessing different selectivity against native PDE6 also showed different potencies against the recombinant and native PDE6s. In particular, one class of xanthine analogues exhibited significantly (5-15-fold) higher potencies for the recombinant PDE6s than for the native enzyme. Our data demonstrates that the recombinant and native PDE6s exhibit differential sensitivity to inhibitors, and cautions the use of recombinant catalytic subunits of PDE6 in drug discovery or in structural/functional studies.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed2004

Syntheses and structures of Ag(I)-containing coordination polymers and Co(II)-containing supramolecular complex based on novel fulvene ligands.

Three new rigid conjugated fulvene ligands L1-L3 were synthesized. L1 and L3 have been prepared by an aroylation reaction of cyclohexyl-substituted cyclopentadienyl anions. L2 was prepared by the reaction of L1 with PhNHNH2 in hot enthanol. Six new coordination polymers, namely [Ag(C25H20N2O2)(ClO4)] x 3.5C6H6 (1), [Ag2(mu-C31H24N4)(eta2-C6H6)(H2O)](ClO4)2 x (C6H6) x (H2O)0.5 (3), [Ag(C31H24N4)]SbF6 x solvate (4), [Ag(C31H24N4)](SbF6)2 x 2C6H6 x CH2Cl2 (5), [Ag(C25H20N2O2)2]SbF6 (6), and [Ag(C25H20N2O2)2]SbF6 (7), and one seven-membered cobaltacycle-containing complex, namely Co(C25H20N2O2)2(C2H5OH)2 (2), were obtained through self-assembly based on these three new fulvene lignads. L2-L3 and compounds 1-7 have been fully characterized by infrared spectroscopy, elemental analysis, and single-crystal X-ray diffraction. The results indicate that the coordination chemistry of new fulvene ligands is versatile. They can bind metal ions not only through the terminal N-donors and fulvene carbon atoms into organometallic coordination polymers but also through the two chelating carbonyl groups into unusual seven-membered metallo-ring supramolecular complexes. In the solid state, ligands L1-L3 are luminescent. A blue-shift in the emission was observed between the free ligand L1 and the one incorporated into Co(II)-containing complex 2, and a red-shift in the emission was observed between the free ligand L3 and the one incorporated into Ag(I)-containing polymeric compounds 6 and 7.

Journal Article↗
PubMed2004

Cholera toxin prevents Th1-mediated autoimmune disease by inducing immune deviation.

Cholera toxin (CT), a major enterotoxin produced by Vibrio cholerae, is known for its properties as a mucosal adjuvant that promotes Th2 or mixed Th1 + Th2 responses. In this study, we explore the ability of CT to act as a systemic adjuvant to counteract the Th1 response leading to experimental autoimmune uveitis. We report that susceptible B10.RIII mice immunized with a uveitogenic regimen of the retinal Ag interphotoreceptor retinoid-binding protein could be protected from disease by a single systemic injection of as little as 2 micro g of CT at the time of immunization. The protected mice were not immunosuppressed, but rather displayed evidence of immune deviation. Subsequent adaptive responses to interphotoreceptor retinoid-binding protein showed evidence of Th2 enhancement, as indicated by reduced delayed-type hypersensitivity in the context of enhanced Ag-specific lymphocyte proliferation and IL-4 production. Ag-specific production of several other cytokines, including IFN-gamma, was not appreciably altered. The inhibitory effect of CT was dependent on the enzymatic A subunit of CT, because the cell-binding B subunit alone could not block disease development. Mice given CT displayed detectable IL-4 levels in their serum within hours of CT administration. This innate IL-4 production was critical for protection, as infusion of neutralizing Ab against IL-4 to mice, given a uveitogenic immunization and treated with CT, counteracted immune deviation and abrogated protection. Our data indicate that systemic administration of CT inhibits experimental autoimmune uveitis by skewing the response to the uveitogenic autoantigen to a nonpathogenic phenotype.

Adjuvants, Immunologic↗
PubMed2004

A solvent-free, SeCN-/(SeCN)3- based ionic liquid electrolyte for high-efficiency dye-sensitized nanocrystalline solar cells.

A solvent-free ionic liquid electrolyte based on the SeCN-/(SeCN)3- redox couple has been employed for high-efficiency dye-sensitized nanocrystalline solar cells. For the first time an alternative redox couple has been identified to rival and even exceed the performance of the iodide/triiodide couple even at full sunlight. Unprecedented 7.5-8.3% power conversion efficiencies under AM 1.5 sunlight have been achieved for photovoltaic devices with solvent-free ionic liquid electrolytes.

Journal Article↗
PubMed2004

Determination of tamsulosin in dog plasma by liquid chromatography with atmospheric pressure chemical ionization tandem mass spectrometry.

A rapid, sensitive and accurate liquid chromatographic-tandem mass spectrometric method is described for the determination of tamsulosin in dog plasma. Tamsulosin was extracted from plasma using a mixture of hexane-ethyl acetate (2:1, v/v) and separated on a C18 column interfaced with a triple quadrupole tandem mass spectrometer. The mobile phase consisting of a mixture of methanol, water and formic acid (80:20:1, v/v/v) was delivered at a flow rate of 0.5 ml/min. Atmospheric pressure chemical ionization (APCI) source was operated in positive ion mode. Selected reaction monitoring (SRM) mode using the transitions of m/z 409-->m/z 228 and m/z 256-->m/z 166.9 were used to quantify tamsulosin and the internal standard, respectively. The linearity was obtained over the concentration range of 0.1-50.0 ng/ml for tamsulosin and the lower limit of quantitation was 0.1 ng/ml. For each level of QC samples, inter- and intra-run precision was less than 5.0 and 4.0% (relative standard deviation (R.S.D.)), respectively, and accuracy was within +/-0.3% (relative error (R.E.)). This method was successfully applied to pharmacokinetic study of a tamsulosin formulation product after oral administration to beagle dogs.

Administration, Oral↗
PubMed2004

Induction of lysosomal and plasma membrane-bound sialidases in human T-cells via T-cell receptor.

Among the three isoenzymes of neuraminidase (Neu) or sialidase, Neu-1 has been suggested to be induced by cell activation and to be involved in IL (interleukin)-4 biosynthesis in murine T-cells. In the present study, we found that antigen-induced airway eosinophilia, a typical response dependent on Th2 (T-helper cell type 2) cytokines, as well as mRNA expression of Th2 cytokines, including IL-4, are suppressed in Neu-1-deficient mice, thereby demonstrating the in vivo role of murine Neu-1 in regulation of Th2 cytokines. To elucidate the roles of various sialidases in human T-cell activation, we investigated their tissue distribution, gene induction and function. Neu-1 is the predominant isoenzyme at the mRNA level in most tissues and cells in both mice and humans, including T-cells. T-cells also have significant levels of Neu-3 mRNAs, albeit much lower than those of Neu-1, whereas the levels of Neu-2 mRNAs are minimal. In human T-cells, both Neu-1 and Neu-3 mRNAs are significantly induced by T-cell-receptor stimulation, as is sialidase activity against 4-methylumbelliferyl- N -acetylneuramic acid (a substrate for both Neu-1 and Neu-3) and the ganglioside G(D1a) [NeuAcalpha2-3Galbeta1-3GalNAcbeta1-4(NeuAcalpha2-3)Galbeta1-4Glcbeta1-cer] (a substrate for Neu-3, but not for Neu-1). The expression of the two sialidase genes may be under differential regulation. Western blot analysis and enzymic comparison with recombinant sialidases have revealed that Neu-3 is induced as a major isoform in activated cells. The induction of Neu-1 and Neu-3 in T-cells is unique. In human monocytes and neutrophils stimulated with various agents, the only observation of sialidase induction has been by IL-1 in neutrophils. Functionally, a major difference has been observed in Jurkat T-cell lines over-expressing Neu-1- and Neu-3. Upon T-cell receptor stimulation, IL-2, interferon-gamma, IL-4 and IL-13 are induced in the Neu-1 line, whereas in the Neu-3 line the same cytokines are induced, with the exception of IL-4. Taken together, these results suggest an important immunoregulatory role for both Neu-1 and Neu-3 in humans.

Animals↗