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  • American Society of Hematology  (2)
  • 2000-2004  (2)
  • 1930-1934
  • 1
    Publication Date: 2004-11-16
    Description: In vivo biopanning with phage displayed peptide libraries has generated a group of peptide probes which bind selectively to the surface of atherosclerotic plaque endothelium. The highest affinity peptide, EKO130, binds to the 78 kDa glucose regulated protein (Grp78). Grp78 has been demonstrated to play a role in numerous pathological processes as well as a possible role in the local cell surface regulation of the coagulation cascade. The goal of this study is to determine the role of Grp78 in coagulation including plasma clotting, factor Xa (Xa) generation, and tissue factor (TF) gene expression. siRNA mediated inhibition of Grp78 results in a marked increase in TF gene expression in bEND.3 endothelial cells and RAW macrophage-like cells. Antibody mediated inhibition of cell surface Grp78 results in increased TF procoagulant activity and TF-dependent Xa generation in both the endothelial and macrophage cell types. These studies are consistent with results from another laboratory demonstrating that Grp78 over-expression inhibits TF mediated initiation and support of the coagulation protease cascade. Thus, our work indicates that Grp78 suppresses TF at both the functional and molecular level by inhibiting both its thrombogenic potential and gene expression.
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
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  • 2
    Publication Date: 2004-11-16
    Description: Recently, a new class of RNAs has been identified that, like mRNAs, are usually transcribed by RNA polymerase II, but lack significant translated open reading frames. They are non-coding RNAs (ncRNAs) that exert roles directly as RNAs, and function as genetic regulators, or riboregulators. In the present study, we discovered a novel very large ncRNA. From differential gene profiling of CD31 positive tumor microvascular endothelial cells from a murine colon carcinoma, we amplified an ~380 bp nucleotide sequence, DP100. This RNA was present in tumor cells as well as tumor vascular endothelium. The full-length DP100 transcript is an ~7 Kb RNA lacking an open reading frame set for more than 66 amino acids. Also the hypothetically predicted proteins lacked significant similarity to known proteins, consistent with identity of DP100 as an unusually large non-coding RNA transcript. Further bioinformatic search demonstrated that the full-length DP100 sequence is highly homologous to the human alpha gene, which encodes an 8.5 Kb, non-coding RNA transcript, and is located in a region implicated in chromosomal abnormalities of human tumors. The full-length DP100, here designated the mouse alpha gene, is evolutionally highly conserved among vertebrates, suggesting its functional significance. The role for this ncRNA in cellular behavior is under investigation.
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
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