Disease relevance of Serpina3f

• The transcription rate of genes like albumin and alpha1-antitrypsin is reduced, while the gene coding for phenylalanine hydroxylase is totally silent, giving rise to phenylketonuria [1].
• In conclusion, this study demonstrated the feasibility of long-term engraftment and stability of transgene expression from genetically modified liver progenitor cells with a recombinant adenoassociated virus vector and implies a novel approach to gene therapy for treatment of liver diseases, such as alpha1-antitrypsin deficiency [2].
• This is the first report of a conformational drug-associated effect on serpins without genetic factors involved. l-Asparaginase treatment induces severe, acquired, and transient type I deficiency of antithrombin (and alpha1-antitrypsin) with intracellular accumulation of the nascent molecule, increasing the risk of thrombosis [3].
• Alpha1-antitrypsin determines the pattern of emphysema and function in tobacco smoke-exposed mice: parallels with human disease [4].
• We used reassortant viruses isolated from crosses of wild-type (wt) reovirus strain, type 1 Lang, and three independent PI viruses, L/C, PI 2A1, and PI 3-1, to identify viral genes that segregate with the capacity of PI viruses to grow in cells treated with ammonium chloride [5].

Psychiatry related information on Serpina3f

• In three brain regions obtained post-mortem from Huntington's disease patients, alpha1-antitrypsin expression was also altered [6].

High impact information on Serpina3f

• We used antibody-coated gold particles viewed by video-enhanced differential interference contrast microscopy to observe the distribution and movement of two cell surface molecules, N-CAM and the 2A1 antigen, on growth cones of cultured cortical neurons [7].
• The DCs express the CD11c leukocyte integrin, the DEC-205 multilectin receptor for antigen presentation, the intracellular granule antigens which are recognized by monoclonal antibodies M342, 2A1, and MIDC-8, very high levels of MHC I and MHC II, and abundant accessory molecules such as CD40, CD54, and CD86 [8].
• However, in pulse-chase protocols, the [3H]thymidine-labeled progeny exhibit many typical dendritic cell features, including abundant MHC class II and a cytoplasmic granular antigen identified by monoclonal antibody 2A1 [9].
• The human alpha1-antitrypsin promoter was chosen to direct expression because it was the most efficient of several tested in yielding expression of alpha1-antitrypsin protein from a retroviral vector in hepatocytes in vivo [10].
• FTF binding sites are found in the promoters of other liver-expressed genes, some encoding liver transcription factors; FTF, liver alpha1-antitrypsin promoter factor LFB2, and HNF-3beta promoter factor UF2-H3beta are probably the same factor [11].

Chemical compound and disease context of Serpina3f

• Two monoclonal antibodies (mAbs) designated 2A1 and 6A4 which had been shown to be directed against Pseudomonas aeruginosa outer membrane lipoprotein I were tested in cyclophosphamide treated mice for their protective ability against P. aeruginosa infection [12].

Biological context of Serpina3f

• {alpha}-1 Antitrypsin Inhibits Caspase-3 Activity, Preventing Lung Endothelial Cell Apoptosis [13].
• C105Y, a synthetic peptide (CSIPPEVKFNKPFVYLI) based on the amino acid sequence corresponding to residues 359-374 of alpha1-antitrypsin, enhances gene expression from DNA nanoparticles [14].
• We demonstrate that plexin processing is mediated by subtilisin-like proprotein convertases, by inhibition with alpha1-antitrypsin Portland, and by mutagenesis of the substrate-cleavage sites [15].
• The S1 sequences of these viruses contained from one to three mutations, and with the exception of PI 2A1 mutations in each S1 gene resulted in changes in the deduced amino acid sequence of sigma1 protein [16].
• We demonstrate that minicircular DNAs devoid of bacterial sequences expressed 45- and 560-fold more serum human factor IX and alpha1-antitrypsin, respectively, compared to standard plasmid DNAs transfected into mouse liver [17].

Anatomical context of Serpina3f

• Immunoinhibition studies suggested that cytochrome P450s (P450s) 2A1 and 2B1 or related forms are the major enzymes involved in the oxidative metabolism of NNK in mouse lung microsomes [18].
• Both these cell types produce some proteins (e.g. albumin, transthyretin, alpha-1 antitrypsin and others) that are also made in the liver where C/EBP is important for their production; thus either fewer factors or different factors govern yolk sac and choroid plexus production of these proteins [19].
• Polymers of Z alpha1-antitrypsin co-localize with neutrophils in emphysematous alveoli and are chemotactic in vivo [20].
• Accumulation of mutant alpha1-antitrypsin Z in the endoplasmic reticulum activates caspases-4 and -12, NFkappaB, and BAP31 but not the unfolded protein response [21].
• In the steady state, Langerhans cells in the skin-draining nodes expressed maturation markers, such as 2A1 and costimulatory molecules CD86 and CD40 [22].

Associations of Serpina3f with chemical compounds

• A model is proposed in which the removal of mannose from multiple attached oligosaccharides directs calnexin in the selection of misfolded alpha1-antitrypsin for degradation by the proteasome [23].
• EDEM3 accelerates glycoprotein ERAD in transfected HEK293 cells, as shown by increased degradation of misfolded alpha1-antitrypsin variant (null (Hong Kong)) and of TCRalpha [24].
• Altered sedimentation of intracellular complexes following treatment with the specific proteasome inhibitor lactacystin, and in combination with mannosidase inhibition, revealed that the removal of mannose from attached oligosaccharides abrogates the release of misfolded alpha1-antitrypsin from calnexin prior to proteasomal degradation [23].
• The estrogen receptors in the resistant sub-lines have also maintained wild-type characteristics with respect to estrogen and anti-estrogen regulation of the estrogen-regulated proteins procathepsin D, alpha1-antitrypsin and a 42-kDa protein [25].
• The gene expression of p1SV-hFIX, p2SV-hFIX, and a plasmid containing a liver-specific apoE enhancer and alpha antitrypsin promoter, pAAV-hAAT-hFIX. were evaluated in various cell lines using polyethylenimine (PEI) as a gene carrier in vitro [26].

Analytical, diagnostic and therapeutic context of Serpina3f

• In situ hybridization, combined with immunocytochemical staining of tissue sections of lung and spleen, shows colocalization of M1204 with the 2A1 and NLDC DC markers [27].
• (v) Populations of migrating DC in organ cultures upregulated markers of maturity (the antigen recognized by monoclonal antibody 2A1, CD86), but retained indicators of immaturity (invariant chain, residual antigen processing function) [28].
• In dissociated cell culture of embryonic cerebral cortex, 2A1 labels the surface of neurons but not glia [29].
• Western blot analysis with antitrypsin antibody showed that 26 and 24 kDa proteins were highly detected in S4 conditioned medium (CM) in comparison to R3 CM [30].
• Pretreatment of mice with either 2 mg of 2A1 or 4 mg of 6A4 in combination with lethally irradiated human leucocytes reduced the mortality after subsequent subcutaneous injection of 100 living P. aeruginosa organisms to 50% of the controls [12].

References