Disease relevance of DEFA1

• Using a combination of reversed-phase and size-exclusion high performance liquid chromatography and an HP-1 radio-immunoassay, three immunoreactive peptides were detected and isolated from the promyelocyte-like cell line, HL-60, and from leukocytes of patients with chronic myelogenous and chronic lymphocytic leukemias [1].
• Microarray analyses were performed and several genes related to HIV biology, including APOBEC3B, DEFA1, and S100 calcium-binding protein genes, were found to be regulated by prostratin [2].
• Under conditions that supported bactericidal activity, HNP-1 sequentially permeabilized the outer membrane (OM) and inner membrane (IM) of E. coli [3].
• Herpes simplex virus (HSV) types 1 and 2, cytomegalovirus, vesicular stomatitis virus, and influenza virus A/WSN were inactivated by incubation with HNP-1 [4].
• We used density gradient sedimentation techniques to demonstrate that HNP-1 bound to HSV-1 in a temperature-dependent manner [4].

Psychiatry related information on DEFA1

• Neither the MRI signal intensity of the globus pallidus nor MRS correlated with neuropsychologic test results [5].
• BACKGROUND: Previous 1H-MR spectroscopy (MRS) studies compared biochemical spectra of persons with dementia with those of healthy control subjects [6].
• Hydrogen-1 MR spectroscopy (MRS) studies demonstrate metabolic differences between patients who have Alzheimer's disease (AD) and cognitive normal age-matched controls [7].
• Hippocampal choline-containing compounds (Cho) determined with 1H MR spectroscopy (MRS) are decreased in major depression episodes and return to baseline levels after antidepressive electroconvulsive therapy (ECT) [8].
• The addition of MRS to the MR imaging provides a higher specificity in tumour detection and can be recommended as a problem-solving modality for patients with elevated PSA levels and suspicious TRUS before biopsy [9].

High impact information on DEFA1

• The condensed array is heterochromatic as it is associated with HP1, histone H3 methylated at lysine 9, and several histone methyltransferases [10].
• Each of these modification states has been implicated in the maintenance of HP1 protein-binding at pericentric heterochromatin, in transcriptional silencing and in centromere function [11].
• Furthermore, by overexpressing a mammalian homologue (M31) of Drosophila melanogaster heterochromatin protein 1 (HP1; refs 7,8) in transgenic mouse lines that exhibit PEV, it is possible to modify the proportion of cells that silence the transgene in a dose-dependent manner [12].
• Heterochromatin is characterized by the methylation of cytosine nucleotides of the DNA, the methylation of histone H3 at lysine 9 (H3 Lys 9), and the specific binding of heterochromatin protein 1 (HP1) to methylated H3 Lys 9 (refs 1-7) [13].
• We studied the potential use of HNP-1 for antibacterial therapy of experimental bacterial infections in mice [14].

Chemical compound and disease context of DEFA1

• We compared the antibacterial activities of purified HNP-1, -2, and -3 against Escherichia coli, Pseudomonas aeruginosa, methicillin-susceptible Staphylococcus aureus, and methicillin-resistant S. aureus strains using the radial diffusion assay [15].
• The combination of HNP-1, isoniazid, and rifampicin was evaluated against Mycobacterium tuberculosis H(37)Rv in vitro, ex vivo, and in vivo, and synergism was observed on the basis of reductions in minimum inhibitory concentrations (MICs) of these agents [16].
• HP1 and MNEI levels inversely correlate in a number of normal and leukemia myeloid cells and show strikingly opposite coordinated changes during differentiation of U937 cell line induced by retinoic acid [17].
• The results show that a delayed (2 weeks after ischemia) increase in T1W SI in the ischemic striatum is associated with significant increases in manganese, calcium, and iron, but without evident accumulation of MRS-visible lipids or hydroxyapatite precipitation [18].
• A false-negative MRS finding (normal lactate/choline but abnormal outcome) was seen in a patient who had an apparent prenatal injury [19].

Biological context of DEFA1

• The alpha-defensin cluster on human chromosome 8p23.1 is one of the better-characterized CNVs, in which high copy number variability affecting the DEFA1 and DEFA3 genes has been reported [20].
• METHODS: Defensin-stimulated gene expression in primary cultures of HCFs was analyzed by real-time PCR after exposure to various concentrations of HNP1 or HBD2 [21].
• Surprisingly, somatic cell hybrid mapping showed that the number of HP-1/3-like genes on isolated copies of chromosome 8 was variable [22].
• Gene copy number experiments established that there were at least two but fewer than five defensin genes with a high level of similarity to the HP-1 cDNA (HP-1/3-like) [22].
• A cDNA insert for defensin HNP-1 (DEF1) has been used to map the gene(s) to human chromosome 8p23 using a mouse/human somatic cell hybrid panel and in situ hybridization to normal human metaphase chromosomes [23].

Anatomical context of DEFA1

• Human cervical epithelial cells incubated with HNP-1 or HD5 accumulated the peptides intracellularly [24].
• Defensins HNP1 and HBD2 stimulation of wound-associated responses in human conjunctival fibroblasts [21].
• The inhibition of LF by human neutrophil protein (HNP-1) was noncompetitive [25].
• HNP-1 rescued murine macrophages from B. anthracis-induced cytotoxicity, and in vivo treatment with HNP-1-3 protected mice against the fatal consequences of LeTx [25].
• In vitro experiments have indicated that ART-1, an enzyme also present in the airway epithelium, specifically modifies Arg(14) of the HNP-1, causing the loss of the peptide's antimicrobial and cytotoxic activity, while preserving its chemotactic activity [26].

Associations of DEFA1 with chemical compounds

• The peptides, HNP-1, HNP-2, and HNP-3, which we have termed defensins, were rich in cystine, arginine, and aromatic residues, but were devoid of free sulfhydryl groups and carbohydrate moieties [27].
• HP-1 is a 30-residue cysteine- and arginine-rich peptide of the human neutrophil primary granule and is the most abundant human representative of the family of peptides variously called defensins and corticostatins [1].
• The first peak was resolved further by C4 reversed phase HPLC and yielded an active fraction shown by NH2-terminal amino acid sequence analysis to contain defensins HNP-1, HNP-2, and HNP-3 [28].
• Recombinant and native HNP-1 purified from PMN were identical as judged by mass spectrometry, retention time in reverse-phase high performance liquid chromatography, migration on acid-urea polyacrylamide gels, and reaction with a conformation-specific antibody [29].
• In def1, a mutant tomato line having a defective octadecanoid pathway, the 48-kDa MBP kinase is activated by wounding and systemin as in the wild-type plants [30].

Other interactions of DEFA1

• These results identify the antimicrobial proteins, CAP37/azurocidin and defensins HNP-1 and HNP-2, as potent neutrophil-derived chemoattractants for T-cells [28].
• Immunohistochemistry revealed lysozyme, lactoferrin, secretory phospholipase A(2), and HNP-1, -2, and -3 to be present in all samples, whereas HBD-1 was present only in some of the healthy and inflamed samples [31].
• The results of amino acid sequencing by Edman degradation and homology studies indicated that P14 was consistent with a peptide, human alpha-defensin 1 (HNP-1) which belongs to the defensin family [32].
• Human PMNs contain four defensins termed HNP-1 to HNP-4 [15].
• The bactericidal action of this peptide in different physicochemical conditions, as well as the evaluation of the synergistic effect of the peptide with mixtures of neutrophil alpha-defensin HNP-1, epithelial beta-defensin HBD-1, cathelicidin LL-37 and lysozyme were studied using the bacterial membrane permeability test [33].

Analytical, diagnostic and therapeutic context of DEFA1

• Recently, ADP-ribosylated human neutrophil-derived peptide (HNP-1, an antimicrobial peptide secreted by immune cells) has been identified in the bronchoalveolar lavage fluid from individuals who smoke cigarettes [26].
• RESULTS: The onset of symptoms was delayed and hospitalizations were fewer in HP2 compared with HP1 (P < 0.05) [34].
• The binding site for HNP-1 on C1q is most likely located on the collagen-like stalks, as a clear, dose-dependent binding of HNP-1 to either intact C1q or to the collagen-like stalks of C1q was demonstrated using enzyme-linked immunosorbent assay (ELISA) [35].
• Using peripheral blood cells from leukapheresis, containing about 90% of polymorphonuclear cells, we could identify HNP-1, -2, and -4 and propeptides of up to 49 amino acids in length, eluted from HLA class II molecules [36].
• Several RCC lines were found to express mRNA as well as the specific peptides of HNP-1, -2, and -3 demonstrated by reverse transcriptase-polymerase chain reaction, mass spectrometric, and flow cytometric analyses [37].

References