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1.
PLoS Genet ; 14(9): e1007640, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30248107

RESUMO

Hair plays an important role in primates and is clearly subject to adaptive selection. While humans have lost most facial hair, eyebrows are a notable exception. Eyebrow thickness is heritable and widely believed to be subject to sexual selection. Nevertheless, few genomic studies have explored its genetic basis. Here, we performed a genome-wide scan for eyebrow thickness in 2961 Han Chinese. We identified two new loci of genome-wide significance, at 3q26.33 near SOX2 (rs1345417: P = 6.51×10-10) and at 5q13.2 near FOXD1 (rs12651896: P = 1.73×10-8). We further replicated our findings in the Uyghurs, a population from China characterized by East Asian-European admixture (N = 721), the CANDELA cohort from five Latin American countries (N = 2301), and the Rotterdam Study cohort of Dutch Europeans (N = 4411). A meta-analysis combining the full GWAS results from the three cohorts of full or partial Asian descent (Han Chinese, Uyghur and Latin Americans, N = 5983) highlighted a third signal of genome-wide significance at 2q12.3 (rs1866188: P = 5.81×10-11) near EDAR. We performed fine-mapping and prioritized four variants for further experimental verification. CRISPR/Cas9-mediated gene editing provided evidence that rs1345417 and rs12651896 affect the transcriptional activity of the nearby SOX2 and FOXD1 genes, which are both involved in hair development. Finally, suitable statistical analyses revealed that none of the associated variants showed clear signals of selection in any of the populations tested. Contrary to popular speculation, we found no evidence that eyebrow thickness is subject to strong selective pressure.

2.
Am J Hum Genet ; 101(6): 913-924, 2017 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-29198719

RESUMO

The genetic basis of earlobe attachment has been a matter of debate since the early 20th century, such that geneticists argue both for and against polygenic inheritance. Recent genetic studies have identified a few loci associated with the trait, but large-scale analyses are still lacking. Here, we performed a genome-wide association study of lobe attachment in a multiethnic sample of 74,660 individuals from four cohorts (three with the trait scored by an expert rater and one with the trait self-reported). Meta-analysis of the three expert-rater-scored cohorts revealed six associated loci harboring numerous candidate genes, including EDAR, SP5, MRPS22, ADGRG6 (GPR126), KIAA1217, and PAX9. The large self-reported 23andMe cohort recapitulated each of these six loci. Moreover, meta-analysis across all four cohorts revealed a total of 49 significant (p < 5 × 10-8) loci. Annotation and enrichment analyses of these 49 loci showed strong evidence of genes involved in ear development and syndromes with auricular phenotypes. RNA sequencing data from both human fetal ear and mouse second branchial arch tissue confirmed that genes located among associated loci showed evidence of expression. These results provide strong evidence for the polygenic nature of earlobe attachment and offer insights into the biological basis of normal and abnormal ear development.


Assuntos
Orelha/anatomia & histologia , Herança Multifatorial/genética , Locos de Características Quantitativas/genética , Adolescente , Adulto , Animais , Região Branquial/anatomia & histologia , Criança , Pré-Escolar , Proteínas de Ligação a DNA/genética , Receptor Edar/genética , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Camundongos , Pessoa de Meia-Idade , Proteínas Mitocondriais/genética , Fator de Transcrição PAX9/genética , Proteínas/genética , Receptores Acoplados a Proteínas-G/genética , Proteínas Ribossômicas/genética , Fatores de Transcrição/genética , Adulto Jovem
3.
Sci Rep ; 7(1): 15329, 2017 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-29127390

RESUMO

Traffic-related air pollution is known to be associated with skin aging manifestations. We previously found that the use of fossil fuels was associated with skin aging, but no direct link between indoor air pollutants and skin aging manifestations has ever been shown. Here we directly measured the indoor PM2.5 exposure in 30 households in Taizhou, China. Based on the directly measured PM2.5 exposure and questionnaire data of indoor pollution sources, we built a regression model to predict the PM2.5 exposure in larger datasets including an initial examination group (N = 874) and a second examination group (N = 1003). We then estimated the association between the PM2.5 exposure and skin aging manifestations by linear regression. In the initial examination group, we showed that the indoor PM2.5 exposure levels were positively associated with skin aging manifestation, including score of pigment spots on forehead (12.5% more spots per increase of IQR, P-value 0.0371), and wrinkle on upper lip (7.7% more wrinkle on upper lip per increase of IQR, P-value 0.0218). The results were replicated in the second examination group as well as in the pooled dataset. Our study provided evidence that the indoor PM2.5 exposure is associated with skin aging manifestation in a Chinese population.

4.
Hum Genet ; 135(11): 1279-1286, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27487801

RESUMO

Hair straightness/curliness is one of the most conspicuous features of human variation and is particularly diverse among populations. A recent genome-wide scan found common variants in the Trichohyalin (TCHH) gene that are associated with hair straightness in Europeans, but different genes might affect this phenotype in other populations. By sampling 2899 Han Chinese, we performed the first genome-wide scan of hair straightness in East Asians, and found EDAR (rs3827760) as the predominant gene (P = 4.67 × 10-16), accounting for 3.66 % of the total variance. The candidate gene approach did not find further significant associations, suggesting that hair straightness may be affected by a large number of genes with subtle effects. Notably, genetic variants associated with hair straightness in Europeans are generally low in frequency in Han Chinese, and vice versa. To evaluate the relative contribution of these variants, we performed a second genome-wide scan in 709 samples from the Uyghur, an admixed population with both eastern and western Eurasian ancestries. In Uyghurs, both EDAR (rs3827760: P = 1.92 × 10-12) and TCHH (rs11803731: P = 1.46 × 10-3) are associated with hair straightness, but EDAR (OR 0.415) has a greater effect than TCHH (OR 0.575). We found no significant interaction between EDAR and TCHH (P = 0.645), suggesting that these two genes affect hair straightness through different mechanisms. Furthermore, haplotype analysis indicates that TCHH is not subject to selection. While EDAR is under strong selection in East Asia, it does not appear to be subject to selection after the admixture in Uyghurs. These suggest that hair straightness is unlikely a trait under selection.


Assuntos
Antígenos/genética , Receptor Edar/genética , Estudo de Associação Genômica Ampla , Cabelo , Proteínas de Filamentos Intermediários/genética , Grupo com Ancestrais do Continente Asiático/genética , China , Grupo com Ancestrais do Continente Europeu/genética , Feminino , Frequência do Gene , Predisposição Genética para Doença , Cabelo/crescimento & desenvolvimento , Cabelo/metabolismo , Cabelo/ultraestrutura , Haplótipos , Humanos , Masculino , Fenótipo , Polimorfismo de Nucleotídeo Único
5.
Hum Genet ; 135(1): 99-108, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26603699

RESUMO

An adaptive variant of human Ectodysplasin receptor, EDARV370A, had undergone strong positive selection in East Asia. In mice and humans, EDARV370A was found to affect ectodermal-derived characteristics, including hair thickness, hair shape, active sweat gland density and teeth formation. Facial characteristics are also largely ectodermal derived. In this study, taking advantage of an admixed population of East Asian and European ancestry-the Uyghur, we aim to test whether EDARV370A is affecting facial characteristics and to investigate its pleiotropic nature and genetic model. In a sample of 1027 Uyghurs, we discover that EDARV370A is significantly associated with several facial characteristics, in particular shape of earlobe (P = 3.64 × 10 (-6) ) and type of chin (P = 9.23 × 10 (-5) ), with successful replication in other East Asian populations. Additionally, in this Uyghur population, we replicate previous association findings of incisors shoveling (P = 1.02 × 10 (-7) ), double incisors shoveling (P = 1.86 × 10 (-12) ) and hair straightness (P = 3.99 × 10 (-16) ), providing strong evidence supporting an additive model for the EDARV370A associations. Partial least square path model confirms EDARV370A systematically affect these weakly related ectodermal-derived characteristics, suggesting the pleiotropic effect of EDARV370A mainly plays roles in early embryo development. This study extends our knowledge about the pleiotropic nature of EDARV370A and provides potential clues to its adaptation fitness in human evolution.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Grupos Étnicos/genética , Grupo com Ancestrais do Continente Europeu/genética , Facies , Receptores da Ectodisplasina/genética , Adolescente , Adulto , Alelos , China , Feminino , Humanos , Masculino , Fenótipo , Adulto Jovem
6.
Plant Physiol ; 167(3): 915-30, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25609556

RESUMO

Whereas the regulatory mechanisms that direct fruit ripening have been studied extensively, little is known about the signaling mechanisms underlying this process, especially for nonclimacteric fruits. In this study, we demonstrated that a SUCROSE NONFERMENTING1-RELATED PROTEIN KINASE2, designated as FaSnRK2.6, is a negative regulator of fruit development and ripening in the nonclimacteric fruit strawberry (Fragaria × ananassa) and can also mediate temperature-modulated strawberry fruit ripening. FaSnRK2.6 was identified as an ortholog of OPEN STOMATA1. Levels of FaSnRK2.6 transcript rapidly decreased during strawberry fruit development and ripening. FaSnRK2.6 was found to be capable of physically interacting with strawberry ABSCISIC ACID INSENSITIVE1, a negative regulator in strawberry fruit ripening. RNA interference-induced silencing of FaSnRK2.6 significantly promoted fruit ripening. By contrast, overexpression of FaSnRK2.6 arrested fruit ripening. Strawberry fruit ripening is highly sensitive to temperature, with high temperatures promoting ripening and low temperatures delaying it. As the temperature increased, the level of FaSnRK2.6 expression declined. Furthermore, manipulating the level of FaSnRK2.6 expression altered the expression of a variety of temperature-responsive genes. Taken together, this study demonstrates that FaSnRK2.6 is a negative regulator of strawberry fruit development and ripening and, furthermore, that FaSnRK2.6 mediates temperature-modulated strawberry fruit ripening.


Assuntos
Fragaria/crescimento & desenvolvimento , Fragaria/metabolismo , Frutas/crescimento & desenvolvimento , Frutas/metabolismo , Proteínas de Plantas/metabolismo , Ácido Abscísico/farmacologia , Sequência de Aminoácidos , Metilação de DNA/efeitos dos fármacos , Fragaria/efeitos dos fármacos , Fragaria/genética , Frutas/efeitos dos fármacos , Frutas/genética , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Genoma de Planta , Modelos Biológicos , Dados de Sequência Molecular , Filogenia , Proteínas de Plantas/química , Proteínas de Plantas/genética , Regiões Promotoras Genéticas/genética , Ligação Proteica/efeitos dos fármacos , Interferência de RNA/efeitos dos fármacos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Homologia de Sequência de Aminoácidos , Frações Subcelulares/efeitos dos fármacos , Frações Subcelulares/metabolismo , Sacarose/farmacologia , Temperatura Ambiente , Fatores de Tempo
7.
Sci China Life Sci ; 57(5): 510-8, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24752358

RESUMO

Teeth are one of the most important materials for anthropological studies because they are likely to be preserved in ancient remains. While the frequencies of dental characteristics can provide clues to the phylogeny of populations, genetic studies at the individual level can further reveal the biological mechanisms and evolutionary context of dental characteristics. In this study, by analyzing 38 dental characteristics of 242 Xinjiang Uyghur individuals, we found that (i) the dental characteristics of the Uyghurs showed evidence of admixture between European and East Asian populations. The admixture proportions were in line with those previously reported in population genetic studies; (ii) the Xinjiang Uyghur dental characteristics formed three clusters in pairwise correlation analysis. One of the main clusters consisted of characteristics including incisor shoveling, double shoveling and mesial ridge; and (iii) all the characteristics in this cluster were significantly correlated with the genetic variant EDARV370A. The extracted composite phenotypic factor was also significantly associated with EDARV370A, which explained 18% of the total phenotypic variance. This indicated a pleiotropic effect, i.e., the same genetic factor affects a number of dental characteristics at the same time. Our results confirmed that EDARV370A, a genetic variant that first originated in East Asia about 30000 years ago, played an important role in incisor shoveling in East Asia. This finding suggested that incisor shoveling in modern humans in East Asia is likely to have appeared after the late Pleistocene.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Receptor Edar/genética , Evolução Molecular , Variação Genética , Dente/anatomia & histologia , Adolescente , Adulto , Modelos Dentários , Grupo com Ancestrais do Continente Europeu/genética , Feminino , Frequência do Gene , História Antiga , Humanos , Incisivo/anatomia & histologia , Masculino , Modelos Genéticos , Mutação de Sentido Incorreto , Fenótipo , Fatores de Tempo , Adulto Jovem
8.
Front Plant Sci ; 5: 63, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24616729

RESUMO

In maize developing seeds, transfer cells are prominently located at the basal endosperm transfer layer (BETL). As the first filial cell layer, BETL is a gateway to sugars, nutrients and water from mother plant; and anchor of numerous functions such as sucrose turnover, auxin and cytokinin biosynthesis/accumulation, energy metabolism, defense response, and signaling between maternal and filial generations. Previous studies showed that basal developing endosperms of miniature1 (mn1) mutant seeds lacking the Mn1-encoded cell wall invertase II, are also deficient for hexose. Given the role of glucose as one of the key sugars in protein glycosylation and proper protein folding; we performed a comparative large scale glycoproteome profiling of total proteins of these two genotypes (mn1 mutant vs. Mn1 wild type) using 2D gel electrophoresis and glycosylation/total protein staining, followed by image analysis. Protein identification was done by LC-MS/MS. A total of 413 spots were detected; from which, 113 spots matched between the two genotypes. Of these, 45 showed >20% decrease/increase in glycosylation level and were selected for protein identification. A large number of identified proteins showed decreased glycosylation levels in mn1 developing endosperms as compared to the Mn1. Functional classification of proteins, showed mainly of post-translational modification, protein turnover, chaperone activities, carbohydrate and amino acid biosynthesis/transport, and cell wall biosynthesis. These proteins and activities were related to endoplasmic reticulum (ER) stress and unfolded protein response (UPR) as a result of the low glycolsylation levels of the mutant proteins. Overall, these results provide for the first time a global glycoproteome profile of maize BETL-enriched basal endosperm to better understand their role in seed development in maize.

9.
Proc Natl Acad Sci U S A ; 110(18): 7482-7, 2013 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-23589856

RESUMO

Glycerophosphocholine (GPC) is high in cells of the renal inner medulla where high interstitial NaCl and urea power concentration of the urine. GPC protects inner medullary cells against the perturbing effects of high NaCl and urea by stabilizing intracellular macromolecules. Degradation of GPC is catalyzed by the glycerophosphocholine phosphodiesterase activity of glycerophosphodiester phosphodiesterase domain containing 5 (GDPD5). We previously found that inhibitory posttranslational modification (PTM) of GDPD5 contributes to high NaCl- and urea-induced increase of GPC. The purpose of the present studies was to identify the PTM(s). We find at least three such PTMs in HEK293 cells: (i) Formation of a disulfide bond between C25 and C571. High NaCl and high urea increase reactive oxygen species (ROS). The ROS increase disulfide bonding between GDPD5-C25 and -C571, which inhibits GDPD5 activity, as supported by the findings that the antioxidant N-acetylcysteine prevents high NaCl- and urea-induced inhibition of GDPD5; GDPD5-C25S/C571S mutation or over expression of peroxiredoxin increases GDPD5 activity; H2O2 inhibits activity of wild type GDPD5, but not of GDPD5-C25S/C571S; and peroxiredoxin is relatively low in the renal inner medulla where GPC is high. (ii) Dephosphorylation of GDPD5-T587. GDPD5 threonine 587 is constitutively phosphorylated. High NaCl and high urea dephosphorylate GDPD5-T587. Mutation of GDPD5-T587 to alanine, which cannot be phosphorylated, decreases GPC-PDE activity of GDPD5. (iii) Alteration at an unknown site mediated by CDK1. Inhibition of CDK1 protein kinase reduces GDE-PDE activity of GDPD5 without altering phosphorylation at T587, and CDK1/5 inhibitor reduces activity of GDPD5- C25S/C571S-T587A.


Assuntos
Glicerilfosforilcolina/metabolismo , Inibidores de Fosfodiesterase/farmacologia , Diester Fosfórico Hidrolases/metabolismo , Processamento de Proteína Pós-Traducional/efeitos dos fármacos , Cloreto de Sódio/farmacologia , Ureia/farmacologia , Sequência de Aminoácidos , Animais , Quinases Ciclina-Dependentes/antagonistas & inibidores , Quinases Ciclina-Dependentes/metabolismo , Glicosilação/efeitos dos fármacos , Células HEK293 , Células HeLa , Humanos , Peróxido de Hidrogênio/farmacologia , Espectrometria de Massas , Proteínas de Membrana/metabolismo , Camundongos , Dados de Sequência Molecular , Proteínas Mutantes/metabolismo , Mutação/genética , Peptídeos/química , Peptídeos/metabolismo , Peroxirredoxinas/metabolismo , Fosforilação/efeitos dos fármacos , Fosfotreonina/metabolismo , Inibidores de Proteínas Quinases/farmacologia
10.
Physiol Genomics ; 44(21): 1063-71, 2012 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-22991206

RESUMO

Mammalian cells are normally stressed by high interstitial NaCl in the renal medulla and by lesser elevation of NaCl in several other tissues. High NaCl damages proteins and DNA and can kill cells. Known protective responses include nuclear translocation of the transcription factor NFAT5 and other proteins. In order better to understand the extent and significance of changes in nuclear protein abundance, we extracted nuclear and cytoplasmic proteins separately from HEK293 cells and measured by LC-MS/MS (iTRAQ) changes of abundance of proteins in the extracts in response to high NaCl at three time points: 1 h, 8 h, and adapted for two passages. We confidently identified a total of 3,190 proteins; 163 proteins changed significantly at least at one time point in the nucleus. We discerned the biological significance of the changes by Gene Ontology and protein network analysis. Proteins that change in the nucleus include ones involved in protein folding and localization, microtubule-based process, regulation of cell death, cytoskeleton organization, DNA metabolic process, RNA processing, and cell cycle. Among striking changes in the nucleus, we found a decrease of all six 14-3-3 isoforms; dynamic changes of "cytoskeletal" proteins, suggestive of nucleoskeletal reorganization; rapid decrease of tubulins; and dynamic changes of heat shock proteins. Identification of these changes of nuclear protein abundance enhances our understanding of high NaCl-induced cellular stress, and provides leads to previously unknown damages and protective responses.


Assuntos
Proteínas Nucleares/metabolismo , Cloreto de Sódio/metabolismo , Núcleo Celular/metabolismo , Células HEK293 , Humanos , Espectrometria de Massas , Proteômica
11.
Am J Physiol Cell Physiol ; 303(10): C1061-9, 2012 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-22992674

RESUMO

The transcription factor nuclear factor of activated T cell 5 (NFAT5) is activated by the stress of hypertonicity (e.g., high NaCl). Increased expression of NFAT5 target genes causes accumulation of protective organic osmolytes and heat shock proteins. Under normotonic conditions (∼300 mosmol/kgH(2)O), NFAT5 is distributed between the nucleus and cytoplasm, hypertonicity causes it to translocate into the nucleus, and hypotonicity causes it to translocate into the cytoplasm. The mechanism of translocation is complex and not completely understood. NFAT5-T298 is a known contact site of NFAT5 with its specific DNA element [osmotic response element (ORE)]. In the present study, we find that mutation of NFAT5-T298 to alanine or aspartic acid not only reduces binding of NFAT5 to OREs (EMSA) but also proportionately reduces high NaCl-induced nuclear translocation of NFAT5. Combined mutation of other NFAT5 DNA contact sites (R293A/E299A/R302A) also greatly reduces both specific DNA binding and nuclear localization of NFAT5. NFAT5-T298 is a potential phosphorylation site, but, using protein mass spectrometry, we do not find phosphorylation at NFAT5-T298. Further, decreased high NaCl-induced nuclear localization of NFAT5 mutated at T298 does not involve previously known regulatory mechanisms, including hypotonicity-induced export of NFAT5, regulated by phosphorylation of NFAT5-S155, XPO1 (CRM1/exportin1)-mediated export of NFAT5 from the nucleus, or hypertonicity-induced elevation of NUP88, which enhances nuclear localization of NFAT5. We conclude that specific DNA binding of NFAT5 contributes to its nuclear localization, by mechanisms, as yet undetermined, but independent of ones previously described to regulate NFAT5 distribution.


Assuntos
DNA/metabolismo , Transporte Proteico/efeitos dos fármacos , Cloreto de Sódio/farmacologia , Fatores de Transcrição/metabolismo , Processamento Alternativo , Animais , Linhagem Celular , Regulação da Expressão Gênica/fisiologia , Humanos , Carioferinas/genética , Carioferinas/metabolismo , Camundongos , Mutação , Pressão Osmótica , Ligação Proteica , Isoformas de Proteínas , Receptores Citoplasmáticos e Nucleares/genética , Receptores Citoplasmáticos e Nucleares/metabolismo , Cloreto de Sódio/química , Fatores de Transcrição/genética
12.
Protein Sci ; 19(1): 174-82, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19937656

RESUMO

The Ara h 2 proteins are major determinants of peanut allergens. These proteins have not been fully studied at the molecular level. It has been previously proposed that there are two isoforms of Ara h 2, based on primary structures that were deduced from two reported cDNA sequences. In this report, four isoforms have been purified and characterized individually. Mass spectrometric methods have been used to determine the protein sequences and to define post-translational modifications for all four isoforms. Two pairs of isoforms have been identified, corresponding to a long-chain form and a form that is shorter by 12 amino acids. Each pair is further differentiated by the presence or absence of a two amino acid sequence at the carboxyl terminus of the protein. Modifications that were characterized include site-specific hydroxylation of proline residues, but no glycosylation was found, in contrast to previous reports.


Assuntos
Albuminas 2S de Plantas/química , Alérgenos/química , Glicoproteínas/química , Prolina/química , Albuminas 2S de Plantas/metabolismo , Alérgenos/metabolismo , Sequência de Aminoácidos , Antígenos de Plantas , Cromatografia por Troca Iônica , Dissulfetos , Glicoproteínas/metabolismo , Hidroxilação , Dados de Sequência Molecular , Peso Molecular , Fragmentos de Peptídeos/química , Prolina/metabolismo , Isoformas de Proteínas/química , Isoformas de Proteínas/metabolismo , Processamento de Proteína Pós-Traducional , Alinhamento de Sequência , Espectrometria de Massas em Tandem
13.
Int J Mass Spectrom ; 278(2-3): 109-113, 2008 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-19956338

RESUMO

This laboratory has introduced a chemical method for residue-specific protein cleavage and has provided a preliminary assessment of the suitability of microwave accelerated acid cleavage as a proteomic tool. This report is a continuing assessment of the fate of common protein modifications in microwave-accelerated acid cleavage. We have examined the cleavage of ribonuclease A and the related N-linked glycoprotein ribonuclease B, and the O-linked glycoprotein alpha crystallin A chain, using MALDI-TOF and LC-ESI-MS to identify the peptide products. RNase A and B each contain four disulfide bonds, and the addition of a reducing reagent, such as dithiothreitol, was found to be required to achieve efficient acidic proteolysis. The linkage of the glycosidic group to the asparagine side-chain in ribonuclease B was found not to be cleaved by brief microwave treatment in 12.5 % acetic acid. The distribution of the heterogeneous carbohydrate side chain in the glycopeptide products of acid cleavage was compared to that of the glycopeptide products of tryptic digestion. Hydrolysis within the carbohydrate chain itself is minimal under the conditions used. The O-linked side-chain on alpha crystalline A was found to be cleaved during acid cleavage of the protein.

14.
Chem Biodivers ; 4(2): 215-23, 2007 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-17311237

RESUMO

The interaction between CT-DNA and the zinc phthalocyanine ZnPc (1) was studied by UV/VIS and fluorescence titration, as well as by thermal denaturation. ZnPc was found to strongly bind to CT-DNA (K(app)=7.35 x 10(5) M(-1)) in a non-intercalative mode. The photosensitized cleavage of pBR322 DNA was found to efficiently proceed via singlet-oxygen ((1)O(2)) production. Further, ZnPc (1) caused site-specific scission of guanine (G) bases around the bulge of the hairpin oligonucleotides OD1-OD3, as clearly shown by gel-electrophoresis experiments.


Assuntos
DNA/metabolismo , Indóis/metabolismo , Conformação de Ácido Nucleico , Compostos Organometálicos/metabolismo , Sondas Moleculares , Desnaturação de Ácido Nucleico , Fotólise , Espectrofotometria Ultravioleta
15.
Zhonghua Shao Shang Za Zhi ; 22(1): 33-7, 2006 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-16680959

RESUMO

OBJECTIVE: To investigate the influence of some topically used antibiotics (amikacin, gentamicin, chloromycetin and sulfamylon), basic fibroblast growth factor (FGF2) , epithelial growth factor (EGF) and recombinant human growth hormone (rhGH) on the growth of fibroblasts in vitro. METHODS: Fibroblasts were cultured and passaged. The cultured cells were then divided into control (routine culture of fibroblasts), amikacin (amikacin in respective dose of 0.021, 0.210, 2.100 mg/L), gentamicin (in respective dose of 5, 50, 500 mg/L) , chloromycetin (in respective dose of 0.01, 0.10, 1.00 mg/L), sulfamylon (in respective dose of 5, 10 g/L), FGF2 (2400 U/ml), EGF (2000 U/ml) and rhGH (0.016, 0.160, 1.600 g/L) groups. After the above agents were added to the culture medium respectively, the proliferation of the cultured fibroblasts was determined with MTT method, and the result was expressed as A (absorption) value. The cell cycle was determined with flow cytometry and the morphology of the cells was observed with inverted microscope. RESULTS: (1) MTT method: The A value of fibroblasts cultured with amikacin, gentamicin, chloromycetin and sulfamylon in various doses was obviously lower than that in control group (0.4553 +/- 0.0217, P < 0.05 or 0.01) , and the A value of sulfamylon group was the lowest in two doses (0.1013 +/- 0.0011 for 5 g/L and 0.0950 +/- 0.0041 for 10 g/L, P < 0.01). On the other hand,the A value in FGF2 and rhGH group(0.016 g/L) was much higher than that in the control (P < 0.05). However,theA value in EGF (both doses) and rhGH groups (0.160, 1.600 g/L) was close to that in control (P > 0.05). (2) Cell cycle determination: The proliferation index (PI) of fibroblasts cultured with amikacin in dose of 0.210 mg/L showed no difference compared to that in control (9.63 +/- 0.45)%, (P > 0.05). But the PI of fibroblasts cultured with FGF2, EGF and rhGF in dose of 0.016 g/L was increased significantly (46.76 +/- 2.33)%, (42.30 +/- 1.41)%, and (13.29 +/- 0.47)%, respectively, (P < 0.05 or 0.01). (3) Histological examination of the cells: The number of fibroblasts in elongated or spindle shape was larger, showing a blur contour but high transparency in control as well as in EGF and rhGH groups (both 0.160 and 1.600 g/L doses groups). The number of cells was lower in amikacin, gentamicin, chloromycetin and sulfamylon groups with sharp but irregular contour and lower transparency, and more granule-like materials and vacuoles in the cytoplasm. The cells in the FGF2 and rhGH (in dose of 0.016 g/L) groups exhibited dense with even distribution and slender or spindle shape and with more mitotic figures but blur contour and high transparency. CONCLUSION: Different kinds of the topically used therapeutic agents for burn wounds exert different influence on the biological characteristics of fibroblasts in vitro. The topically used agents for burn wounds should be carefully selected so that wound healing will be promoted and scar formation inhibited.


Assuntos
Antibacterianos/farmacologia , Proliferação de Células/efeitos dos fármacos , Fator de Crescimento Epidérmico/farmacologia , Fator 2 de Crescimento de Fibroblastos/farmacologia , Fibroblastos/efeitos dos fármacos , Hormônio do Crescimento Humano/farmacologia , Ciclo Celular , Células Cultivadas , Fibroblastos/citologia , Humanos , Técnicas In Vitro , Cicatrização/efeitos dos fármacos
16.
Zhonghua Shao Shang Za Zhi ; 18(3): 183-5, 2002 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-12460519

RESUMO

OBJECTIVE: To explore the influence of recombinant human growth hormones (rhGH) postburn systemic metabolism. METHODS: Twenty-four burn patients were randomly and equally divided into treatment and control groups. Same amount of rhGH (9 U/d) or isotonic saline was injected subcutaneously to respective patients during 3 approximately 17 postburn days (PBDs). Blood samples were harvested at 3, 10 and 17 PBDs for the determination of serum growth hormone, insulin-like growth factor (IGF-1), insulin-like growth factor binding protein-3 (IGFBP-3), serum proteins, plasma insulin, plasma glucagons and blood glucose, which were then compared and analyzed between two the groups. RESULTS: The serum levels of GH, IGF-1, IGFBP-3, serum prealbumin and transferrin in rhGH treatment group were evidently higher than those in control groups at 10 and 17 PBDs (P < 0.05 approximately 0.01). But there was no obvious difference in serum albumin, plasma insulin, glucagon and blood glucose (P > 0.05). CONCLUSION: Small dose of rhGH could promote systemic protein synthesis with no side effects on blood glucose levels.


Assuntos
Queimaduras/sangue , Hormônio do Crescimento/farmacologia , Adolescente , Adulto , Proteínas Sanguíneas/efeitos dos fármacos , Proteínas Sanguíneas/metabolismo , Feminino , Hormônio do Crescimento/sangue , Humanos , Insulina/sangue , Fator de Crescimento Insulin-Like I/análise , Fator de Crescimento Insulin-Like I/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Proteínas Recombinantes/farmacologia
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