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Biomedical subjects

Wei Sun

Publications and source records attributed to Wei Sun.

At least 55 records · Page 3Linked to original sources
PubMed2006

[Alpha-galactosidase A gene mutation in a Chinese family with Fabry disease mimicking clinical features of hypertrophic cardiomyopathy].

OBJECTIVE: To screen gene mutation in alpha-galactosidase A (alpha-Gal A) in a nonconsanguineous Chinese family with Fabry disease (FD) with clinical manifestations similar to hypertrophic cardiomyopathy (HCM). METHODS: Mutation analysis was performed by using purified PCR products to direct sequence analysis on an ABI-377XL automated DNA sequencer. DNA analysis of alpha-Gal A gene and physical and clinical examinations were performed in a female proband and in her relatives (15 subjects in total). RESULTS: Three hemizygotes and 6 heterozygotes were diagnosed for FD by the alpha-Gal A gene analysis with a missense mutation in exon 5 of the alpha-Gal A sequence, leading to a TGG32TGA substitution, which may induce the absent of tryptophan's translation (corresponded to TGG) by the terminator codon TGA. Six patients in the family were revealed as HCM by echocardiography. CONCLUSIONS: Present results show that it is important to differentiate FD from other causes of hypertrophy in patients with cardiac hypertrophy. Screening for alpha-Gal A gene mutations in patients with FD and in their relatives could help to identify all suspected cases within the families.

Adolescent↗
PubMed2006

[The study of 11 cases of chordoma in the skull base or neck].

OBJECTIVE: To study the clinical manifestation, histopathological types, radiological characteristics, surgical methods and the prospective efficacy of chordoma in the skull base and neck. METHOD: Analyzed the characteristics about eleven patients with chordoma in the skull base or neck that we had treated in our department from 1985 to 2003 and introduced a case of a huge chordoma in the neck. All of the patients were treated by surgery. RESULT: The clinical manifestations of chordoma in the neck or skull base were complex. The first symptoms included the mass in the neck, rhinocleisis, visuognosis fall, tinnitus, hearing loss, and damages of brain nerves. Eight cases were the typical chordoma and the other three were the cartilaginiform chordoma. The dilatant image of parenchyma was the feature in CT scan and the images often had clear confines. The cervical vertebra and the skull base were damaged in the most of the cases. Four patients (4/11) recrudesced in two years after the surgery, and eight of eleven were living more than five years after the surgery. CONCLUSION: The clinical manifestations of chordoma in the neck or skull base were complex. The cervical vertebra and the skull base were often damaged in the most of the cases. Surgery is an effective method on chordoma. The surgery path should be selected according

Adult↗
PubMed2006

[Experimental study of effect of tanshinone on artery restenosis in rat carotid injury model].

OBJECTIVE: To observe the preventive and therapeutic effect of tanshinone (TA) on artery restenosis in the rat carotid injury model and explor the mechanism. METHOD: Male SD rats were randomly divided into model control group, and low dose, moderate dose and high dose TA groups. Each group had 10 rats. The rats in the high, moderate and low dose groups were respectively fed with TA 120, 40,13.3 mg x kg(-1) x d(-1) by gast rogavage; the rats in the model control group were fed with the same volume solvent. Two days later, the rat's right carotid artery was injuried by balloon dilatation to induce intimal thickening for establishing the restenosis model. After 2 weeks of treatment, the artery was harvested and stained by hematoxylin-elsin (HE) and immunohistochemistry of PCNA, NF-kappaB and iNOS. The morphological changes were checked under microscope. The area of the intimal and medial layer of the vessels, and their ratios were analyzed with image analysis software. The expression level of PCNA, NF-kappaB and iNOS were used as the positive index. RESULT: The intimal area and intima-to-media ratio of the injuried artery increased obviously, suggesting the model was successful. Compared with the model group, TA significantly decreased the intimal area and intima-to-media ratio (P < 0.05), and also decreased the positive index of PCNA and the positive ratio of NF-kappaB and iNOS (P < 0.05). CONCLUSION: TA can effectively inhibit intimal thickening and inflammation. This result suggestes that TA may play a positive role in the prevention of restenosis after PTCA.

Abietanes↗
PubMed2006

[Comparative study on the resistance of Bacteriophage phi chi 174D, T4 and f2 to an iodophor in laboratory].

BACKGROUND: To screen for the most resistant bacteriophage as indicator in disinfection tests, the resistance of bacteriophage phi chi 174D, T4 and f2 to iodophor were observed in laboratory. METHODS: The virucidal activity of iodophor against bacteriophage phi chi 174D, T4, and f2 were assessed by suspension test. The neutralizer is selected and appraised by testing with neutralizer. Bacteriophage phi chi 174D, T4, and f2 were detected and enumerated by the double-agar-layer plaque technique. RESULTS: (1) With 500 mg/L of available iodine of iodophor solution, within a contact time of 40 min, or 750 mg/L, 10 min, or 1000 mg/L, 5 min, the reduction of bacteriophage phi chi 174D could achieve the "disinfection" level [log10 inactivation value (LIV) or log10 reduction value (LRV) of bacteriophage phi chi 174D (log10 No-log10 Nt) was > or = 4.00 log10]. (2) With 600 mg/L of available iodine of iodophor solution, within a contact time of 40 min, or 700 mg/L, 5 min, the reductions of bacteriophage T4 could achieve the "disinfection" level. (3) With 50 mg/L of available iodine of iodophor solution, within a contact time of 10 min, or 75 mg/L, 10 min, the reductions of bacteriophage f2 could achieve the "disinfection" level. CONCLUSION: The order of resistance of the above three bacteriophages to iodophor from greatest to smallest is as follows: bacteriophage phi chi 174D greater than bacteriophage T4 > bacteriophage f2.

Bacteriophage T4↗
PubMed2006

[Development of radioimmunoassay for human sperm protein 17].

OBJECTIVE: To develop a method of radioimmunoassay for human sperm protein 17(Sp17) determination. METHODS: Anti-recombinant human Sp17 antibody was prepared, the labeling of 125I-rhSp17 performed by chloramine T method, and radioimmunoassay of Sp17 developed. RESULTS: The assay range was 3.3 to approximately 800 microg/L, the sensitivity was 2.0 microg/L, and the intra- and inter-assay coefficients of variation (CV) were 7.5% to approximately 9.8% and 8.2% to approximately 13.2%, respectively. The serum Sp17 level in normal subjects was (15.60 +/- 7.66) microg/L (n = 59). CONCLUSION: This radioimmunoassay of Sp17 fulfills the reasonable requirements of clinical routine and scientific studies in terms of specificity, sensitivity and practicability. Measurement of Sp17 concentration is useful for assessing its native distribution and aberrant expression.

Animals↗
PubMed2006

[A method using long primers for cloning the upstream sequence of delta-6 fatty acid desaturases gene of Thamnidium elegans by nested inverse PCR].

Thamnidium elegans is a kind of phycomycete that produces essential unsaturated fatty acids, particularly y-linolenic acid. In this process, delta6-Fatty acid desaturase (D6D) plays a key role due to its enzymatic properties that catalyze the delta6 site dehydrogenation of precursor linoleic acid (18:2delta(9, 12) n-6) and a-linolenic acid (18:3delta(9, 12, 15) n-3). This reaction is the first and rate-limiting step of highly unsaturated fatty acids (HUFA) synthesis pathways. After we have isolated and cloned the gene coding delta6-fatty acid desaturase from Thamnidium elegans As3.2806 (GenBank accession number DQ099380), our interest focuses on the promotion and regulation of the gene transcription. To achieve this aim, we designed long primers and used nested inverse PCR to amplify DNA flanking sequences. First, genome of Thamnidium elegans was extracted and digested with restriction enzymes EcoR I and Kpn I , respectively. Then we ligated the digested DNA with T4 ligase at low concentration which is propitious for linear DNA to joint intromolecule. According to the sequence of delta6-fatty acid desaturase gene of Thamnidium elegans, we designed a couple of 35nt long inverse primers and two couples of shorter inverse primers for inverse PCR. Three rounds of PCR reactions were performed. In the primary reaction, the ligated DNA was used as a template, and the product was used as the template of the secondary reaction, the tertiary reaction was achieved in the same way. After all the three rounds of reactions, we got a nice product about 4 kb from the EcoR I digested sample, in which a 1.3kb 5' upstream sequence (GenBank accession number DQ309425) of delta6-fatty acid desaturase gene containing several putative regulatory elements including TATA. box, FSE-2, AP-1 sites, CCAAT cis-element site and STRE-binding site was derived after sequencing. All of these implied intensely that this 1.3kb fragment is a condition-regulated promoter. It is the first report about Thamnidium elegans detla6-fatty acid desaturase gene promoter. The procedure described here is a rapid and simple method and particularly useful to isolate flanking sequences from fungal genome. box, FSE-2, AP-1 sites, CCAAT cis-element site and STRE-binding site was derived after sequencing. All of these implied intensely that this 1.3 kb fragment is a condition-regulated promoter. It is the first report about Thamnidium elegans delta6-fatty acid desaturase gene promoter. The procedure described here is a rapid and simple method and particularly useful to isolate flanking sequences from fungal genome.

Base Sequence↗
PubMed2006

[The expression and DNA sequence of recombination activating gene-1 in nasal membrane of allergic rhinitis].

OBJECTIVE: To study the mechanism of recombination activating gene-1 in pathogenesis of allergic rhinitis and its relation to interleukin-4 (IL-4), interleukin-10 (IL-10) and immunoglobin E (IgE). METHOD: Three groups of allergic rats models were established with ovalbumin (OVA) and intervened with Dexamethasone (DEX). The times of sneeze were recorded, the cutaneous reaction of rats to the passive cutaneous allergen access (PCA) were investigated and the expression and DNA sequence of recombination activating gene-1 were examined and tested with reverse transcription-polymerase chain reaction (RT-PCR) and DNA analysator. The serum levels of IL-4, IL-10 and IgE were examined and tested with enzyme linked immunosorbent assay (ELISA) method in comparison with the controls. RESULT: RAG-1 mRNA expression was not found in normal nasal membrane. Both in AR group and DEX intervention group were seen different expressions; DNA sequence determination didn't find mutation of RG1 genes. The serum level of IL-4[(106.31 +/- 12.90) ng/L] and IgE[(38.67 +/- 4.13) ng/L] in AR group were significantly higher than those in normal control [(93.65 +/- 7.78) ng/L, (23.27 +/- 1.36) ng/L respectively] (P < 0.05), but the IL-10 level [(38.15 +/- 4.89) ng/L] in AR group was significantly lower than those in normal control [(48.74 +/- 3.49) ng/L] (P < 0.05). After DEX intervention, the serum level of IL-4[(92.67 +/- 16.40) ng/L] and IgE[(24.23 +/- 4.38) ng/L] significantly dropped as compared with AR group (P < 0.05) while IL-10[(46.18 +/- 5.01) ng/L] significantly rose (P < 0.05). CONCLUSION: It proves that the high expression of recombination activating genes is closely related to the pathogenesis of allergic rhinitis, which leads to the secretion of IL-4 and inhibits that of IL-10 and whose sequence is conservative in the nasal mucosa of AR. As glucocorticoid does not affect the expression of RAG-1 genes, it suggests that RAG-1 may be an immunomodulator on a higher level in the pathogenesis of AR.

Animals↗
PubMed2006

[Diagnosis of recurrent or residual nasopharyngeal carcinomas in the skull base area with F-18-fluoro-deoxyglucose positron emission tomography].

OBJECTIVE: To investigate the diagnostic value of F-18-fluoro-deoxyglucose positron emission tomography (FDG-PET) for the recurrent or residual nasopharyngeal carcinomas in the skull base area. METHODS: Nine post-irradiation nasopharyngeal carcinoma patients did FDG-PET scanning, CT/MRI imaging and underwent nasopharynx and skull base-biopsy under endoscopy. The results of FDG-PET were evaluated and compared with CT/MRI studies and biopsies. RESULTS: In 9 cases of post-irradiation nasopharyngeal carcinoma, CT/MRI detected 7 recurrent cases and 2 suspected recurrent cases in occipital bone and clivus. All 9 cases had accumulated FDG in nasopharynx and cranial base. A definite diagnosis was made by biopsy, 3 cases were confirmed recurrence, and others 6 cases were proved mucous chronic inflammation and (or) osteoradionecrosis. The accuracy of FDG-PET was 33.3% (3/9), and the false positive rate was 66.7% (6/9). CONCLUSIONS: Diagnosis of recurrent or residual nasopharyngeal carcinomas in the skull base area with FDG-PET had high false-positive rate, final diagnosis must depend on histopathologic examination under endoscopy.

Adult↗
PubMed2006

[Spectrophotometric determination of heparin with neutral red].

The interaction of neutral red and heparin was studied by UV-Vis spectrophotometry in pH 3.0 Britton-Robinson (B-R) buffer solution. Neutral red has a strong absorbance at 523 nm and the addition of heparin into neutral red solution resulted in the decrease in the absorbance value at 523 nm without the appearance of new absorbance peak. The decrease in absorbance value was linear with the concentration of heparin. The conditions for the interaction were optimized and the interferences of coexistent substances were investigated. Under the optimal conditions a linear regression equation was obtained as deltaA = 0.044 + 0.076c (mg x L(-1)) (n = 12, r = 0.997) in the range of 0.10-15.0 mg x L(-1) with the detection limit of 0.073 mg x L(-1). The molar absorptivity of the method was calculated to be 2.037 x 10(6) L x mol(-1) x cm(-1). The method was applied to determine the heparin sodium injection solution with satisfactory results. The stoichiometry of heparin with neutral red was calculated as 1 : 3.

Heparin↗
PubMed2006

[Cardiac valve MCSF-1 and its receptor expression changes in Staphylococcus aureus induced infective endocarditis].

OBJECTIVE: To explore the cellular immunology mechanism of infective endocarditis (IE), we investigated the effects of Staphylococcus aureus (S. aureus) on MCSF-1 and its receptor (c-fms) gene expression in cardiac valves. METHODS: Thirty-two rabbits were divided into 4 groups: mitral or tricuspid valve artificial lesions with 5 x 10(4) CFU or 5 x 10(6) CFU S. aureus injection. Control rabbits (n = 7) received 5 x 10(6) CFU S. aureus injection. IE after operation were confirmed by naked eyes and electron microscope observations. MCSF-1, c-fms in mitral and tricuspid valves were detected by RT-PCR. RESULTS: Twenty-six rabbits survived the operation and 14 rabbits developed IE (2 with 5 x 10(4) CFU and 12 with 5 x 10(6) CFU S. aureus injection) one day post operation. S. aureus injection alone did not induce IE. Compared to control rabbits, MCSF-1 mRNA was significantly upregulated and c-fms mRNA significantly downregulated after 5 x 10(4) CFU S. aureus injection with heart valve artificial lesion in mitral valves or tricuspid valves. MCSF-1 expression in mitral valves was further increased while remained unchanged in tricuspid valve after 5 x 10(6) CFU S. aureus injection compared to that in 5 x 10(4) CFU S. aureus injection group. CONCLUSION: High dose bacterial invasion and heart valves lesion were the main factors for inducing infective endocarditis. Development of infective endocarditis was associated with valve MCSF-1/c-fms expression changes in this rabbit model.

Animals↗
PubMed2006

[Effects of multi-glycoside of Tripterygium wilfordii Hook. f. on proteinuria and expression of slit diaphragm-associated molecules in rats with anti-thy1.1 glomerulonephritis].

OBJECTIVE: To examine the effect of multi-glycoside of Tripterygium wilfordii Hook. f. (GTW) on proteinuria and expression of slit diaphragm-associated molecules such as nephrin and podocin in glomerulonephritis induced by anti-Thy1.1 antibody (anti-Thy1 . 1 GN). METHODS: Anti-Thy1.1 GN was induced in rats by a single intravenous injection with 500 microg of anti-Thy1.1 mAb 1-22-3. Fourteen rats were randomly divided into 2 groups, the GTW-treated group and vehicle treated group, and sacrificed on day 14 in Experiment 1 or on day 7 in Experiment 2 after induction of Anti-Thy1.1 GN. Daily oral administration of GTW and vehicle as a control was started from 3 days before injection or at the same time of injection to the day of sacrifice in Experiment 1 or 2. Proteinuria was determined during 14 days in Experiment 1 or during 7 days in Experiment 2. From kidneys taken at sacrifice, glomerular morphological changes, glomerular macrophage infiltration, glomerular expression of nephrin and podocin, and its mRNA expression in renal tissue were examined. RESULTS: In Experiment 1, proteinuria and mesangial matrix expansion were significantly attenuated by GTW treatment. No difference in staining intensity of nephrin and podocin in glomeruli was observed between GTW treated group and vehicle treated group on day 14. In Experiment 2, GTW treatment significantly ameliorated proteinuria, mesangial injury and activated macrophage infiltration in glomerulus. In addition, it significantly increased the expression of nephrin and podocin and its mRNA expression in glomeruli on day 7. CONCLUSION: In anti-Thy1.1 GN, the reduced expression of nephrin and podocin may contribute to the development of mesangial injury and proteinuria. The findings suggest that GTW ameliorates not only proteinuria but also mesangial lesions in anti-Thy1 . 1 GN most likely by increasing the expression of nephrin and podocin.

Animals↗
PubMed2006

[Clinical characteristics of Candida septicemia seen in a neonatal intensive care unit: analysis of 9 cases].

OBJECTIVE: To analyze the clinical characteristics of Candida septicemia occurred in neonatal intensive care unit (NICU). METHODS: The clinical characteristics of 9 confirmed cases with septicemia caused by Candida species yeasts were analyzed and summarized. RESULTS: All the 9 cases were preterm infants, including 6 cases of very low birth weight infants. All these cases were treated with broad-spectrum antibiotics and parenteral nutrition before fungal infections occurred. Eight cases had percutaneous inserted central catheter (PICC). Three cases had been on ventilator. The symptoms of fungal infection were presented at 8 to 22 days of age. Apnea, poor perfusion and lethargy were common symptoms of these cases with fungal infection. Seven of the 9 cases developed thrombocytopenia. C reactive protein was elevated in 7 cases. Blood culture showed C. albicans in 1 case, C. parapsilosis in 2 cases, and C. guilliermondii in 6 cases. In 5 cases PICC culture showed the same fungus as blood culture revealed at the same time. All the 9 patients received antifungal therapy. Six patients were cured, two died and in one patient the treatments were given up by the parents. CONCLUSIONS: The high risk factors of Candida septicemia in newborn infants include preterm, PICC, broad-spectrum antibiotic therapy and mechanical ventilation. The clinical presentations are always nonspecific. Thrombocytopenia and elevated C reactive protein are common in Candida septicemia patients. Early-started antifungal therapy can improve the prognosis.

Antifungal Agents↗
PubMed2005

Safety and pharmacokinetics of human serum butyrylcholinesterase in guinea pigs.

Human serum butyrylcholinesterase (Hu BChE) has been demonstrated to be a highly effective detoxifying enzyme for counteracting the acute toxicity of organophosphorus (OP) nerve agents. In order to initiate an investigational new drug (IND) application for human use, the safety and pharmacokinetic properties of the enzyme were assessed in guinea pigs. Sixty milligrams per kilogram of Hu BChE was administered to guinea pigs by either i.p. or i.m. injection. Blood was drawn at various time points for up to 2 weeks following enzyme injection for the measurement of blood BChE activity. Hu BChE displayed a mean residence time of 110 h, regardless of the route of administration and the enzyme activity remained almost 10-fold above baseline level even after 2 weeks post enzyme injection. Fourteen days post Hu BChE administration, all animals were subjected to 20 panel serum chemistry, hematology, and complete gross/histopathology examination. Results showed no toxic effects as measured by general observation, serum chemistry, hematology, and gross and histological tissue changes. In conclusion, Hu BChE displays a long-lasting stability in the circulation of guinea pigs, and is devoid of any toxic side effects. These results provide convincing data for the safe and effective use of Hu BChE as a bioscavenger to protect humans against all OP nerve agents.

Animals↗
PubMed2005

Microwave-assisted protein preparation and enzymatic digestion in proteomics.

The combinations of gel electrophoresis or LC and mass spectrometry are two popular approaches for large scale protein identification. However, the throughput of both approaches is limited by the speed of the protein digestion process. Present research into fast protein enzymatic digestion has been focused mainly on known proteins, and it is unclear whether these results can be extrapolated to complex protein mixtures. In this study microwave technology was used to develop a fast protein preparation and enzymatic digestion method for protein mixtures. The protein mixtures in solution or in gel were prepared and digested by microwave-assisted protein enzymatic digestion, which rapidly produces peptide fragments. The peptide fragments were further analyzed by capillary LC and ESI-ion trap-MS or MALDI-TOF-MS. The technique was optimized using bovine serum albumin and then applied to human urinary proteins and yeast lysate. The method enabled preparation and digestion of protein mixtures in solution (human urinary proteins) or in gel (yeast lysate) in 6 or 25 min, respectively. Equivalent (in-solution) or better (in-gel) digestion efficiency was obtained using microwave-assisted protein enzymatic digestion compared with the standard overnight digestion method. This new application of microwave technology to protein mixture preparation and enzymatic digestion will hasten the application of proteomic techniques to biological and clinical research.

Chromatography, Liquid↗
PubMed2005

Concanavalin A-captured glycoproteins in healthy human urine.

Both the urinary proteome and its glycoproteome can reflect human health status, and more directly, functions of kidney and urinary tracts. Because the high abundance protein albumin is not N-glycosylated, the urine N-glycoprotein enrichment procedure could deplete it, and urine proteome could thus provide a more detailed protein profile in addition to glycosylation information especially when albuminuria occurs in some kidney diseases. In terms of describing the details of urinary proteins, the urine glycoproteome is even a better choice than the proteome itself. Pooled urine samples from healthy volunteers were collected and acetone-precipitated for proteins. N-Linked glycoproteins enriched with concanavalin A affinity purification were separated and analyzed by SDS-PAGE-reverse phase LC/MS/MS or two-dimensional LC/MS/MS. A total of 225 urinary proteins were identified based on two-hit criteria with reliability over 97% for each peptide. Among these proteins, 94 were identified in previous urine proteome works, 150 were annotated as glycoproteins in Swiss-Prot, and 43 were predicted as glycoproteins by NetNGlyc 1.0. A number of known biomarkers and disease-related glycoproteins were identified. Because changes in protein quantity or the glycosylation status can lead to changes in the concanavalin A-captured glycoprotein profile, specific urine glycoproteome patterns might be observed for specific pathological conditions as multiplex urinary biomarkers. Knowledge of the urine glycoproteome is important in understanding kidney and body function.

Concanavalin A↗
PubMed2005

Human serum butyrylcholinesterase: in vitro and in vivo stability, pharmacokinetics, and safety in mice.

The use of exogenously administered cholinesterases (ChEs) as bioscavengers of highly toxic organophosphate (OP) nerve agents is now sufficiently well documented to make them a highly viable prophylactic treatment against this potential threat. Of the ChEs evaluated so far, human serum butyrylcholinesterase (HuBChE) is most suitable for human use. A dose of 200 mg (3 mg/kg) of HuBChE is envisioned as a prophylactic treatment in humans that can protect from an exposure of up to 2 x LD50 of soman. In addition to its use as a prophylactic for a variety of wartime scenarios, including covert actions, it also has potential use for first responders (civilians) reacting to terrorist nerve gas release. We recently, developed a procedure for the large-scale purification of HuBChE, which yielded approximately 6 g of highly purified enzyme from 120 kg of Cohn fraction IV-4. The enzyme had a specific activity of 700-750 U/mg and migrated as a single band on SDS-PAGE. To provide data for initiating an investigational new drug (IND) application for the use of this enzyme as a bioscavenger in humans, we established its pharmacokinetic properties, examined its safety in mice, and evaluated its shelf life at various temperatures. In mice administered various doses up to 90 mg/kg, enzyme activity reached peak levels in circulation at 10 and 24 h following i.p. and i.m. injections, respectively. The enzyme displayed a mean residence time (MRT) of 40-50 h, regardless of the route of administration or dose of injected enzyme. Mice were euthanized 2 weeks following enzyme administration and tissues were examined grossly or microscopically for possible toxic effects. Results suggest that HuBChE does not exhibit any toxicity in mice as measured by general observation, serum chemistry, hematology, gross or histologic tissue changes. The shelf life of this enzyme stored at 4, 25, 37, and 45 degrees C was determined in lyophilized form. The enzyme was found to be stable when stored in lyophilized form at -20, 4, 25, or 37 degrees C to date (2 years), as measured by specific activity and SDS polyacrylamide gel electrophoresis. The effect of storage on circulatory stability was determined by measuring MRT in mice; there was no change in the MRT of lyophilized enzyme stored at -20 degrees C to date (2 years). These results provide convincing data that HuBChE is a safe bioscavenger that can provide protection against all OP nerve agents. Efforts are now underway to prepare the required documentation for submission of an IND application to the United States Food and Drug Administration (USFDA).

Animals↗
PubMed2005

The conserved Leu-724 residue is required for both serine phosphorylation and co-activator recruitment for Stat1-mediated transcription activation in response to interferon-gamma.

The signal transducer and activator of transcription (STAT) proteins, a family of latent cytoplasmic transcription factors, become activated in response to extracellular ligand binding to cell surface receptors through tyrosine phosphorylation. Concurrently, a serine phosphorylation event in the transcription activation domain (serine 727 for Stat1) occurs. This serine phosphorylation is essential for the maximal transcription activity of Stat1. Here we show that, in addition to the Ser-727 residue and its phosphorylation, the conserved Leu-724 residue is also essential for gene activation mediated by Stat1. When Leu-724 is mutated to Ala, phosphorylation of Stat1 Ser-727 is defective both in vivo and in vitro. Surprisingly, we found a StatL724I mutant that lacks transcription activity despite normal Ser-727 phosphorylation. Further analyses show that Leu-724, as well as the phospho-Ser-727, are essential for the recruitment of the transcription co-activator CBP/p300 to the promoters of Stat1 target genes. Our results demonstrate that the conserved Leu-724 residue is a key residue that controls the maximal transcription activities of Stat1 in IFN-gamma signaling.

Base Sequence↗