Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pigment epithelium-derived factor (PEDF) is an extracellular multifunctional protein belonging to the serpin superfamily with demonstrable neurotrophic, gliastatic, neuronotrophic, antiangiogenic, and antitumorigenic properties. We have previously provided biochemical evidence for high affinity PEDF-binding sites and proteins in plasma membranes of retina, retinoblastoma, and CNS cells. This study was designed to reveal a receptor involved in the biological activities of PEDF. Using a yeast two-hybrid screening, we identified a novel gene from pigment epithelium of the human retina that codes for a PEDF-binding partner, which we term PEDF-R. The derived polypeptide has putative transmembrane, intracellular and extracellular regions, and a phospholipase domain. Recently, PEDF-R (TTS-2.2/independent phospholipase A(2) (PLA(2))zeta and mouse desnutrin/ATGL) has been described in adipose cells as a member of the new calcium-independent PLA(2)/nutrin/patatin-like phospholipase domain-containing 2 (PNPLA2) family that possesses triglyceride lipase and acylglycerol transacylase activities. Here we describe the PEDF-R gene expression in the retina and its heterologous expression by bacterial and eukaryotic systems, and we demonstrate that its protein product has specific and high binding affinity for PEDF, has a potent phospholipase A(2) activity that liberates fatty acids, and is associated with eukaryotic cell membranes. Most importantly, PEDF binding stimulates the enzymatic phospholipase A(2) activity of PEDF-R. In conclusion, we have identified a novel PEDF-R gene in the retina for a phospholipase-linked membrane protein with high affinity for PEDF, suggesting a molecular pathway by which ligand/receptor interaction on the cell surface could generate a cellular signal.
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PMID:Identification of a lipase-linked cell membrane receptor for pigment epithelium-derived factor. 1703 52

We developed a novel gene delivery system capable of endosome disruption using a polysaccharide-based cationic nanogel composed of a hexadecyl group-bearing cationic cycloamylose nanogel (C16-catCA nanogel) and phospholipaseA(2) (PLA(2)) to hydrolyze membrane phospholipids. C16-catCA nanogel formed nanoparticles with PLA(2) and pDNA by hydrophobic and electrostatic interactions. Both pDNA and PLA(2) were effectively internalized into cells by the C16-catCA nanogel. In addition, the pDNA expression level was enhanced when complexed with specific concentrations of PLA(2). PLA(2) complexed with C16-catCA nanogel also showed a similar hemolytic activity against red blood cells to that observed using native PLA(2). These results suggest that the C16-catCA nanogel/PLA(2) complex possesses membrane disruption ability when delivered into cells and triggers the subsequent release of pDNA from the endosome to the cytoplasm. This is the first report of co-delivery of pDNA and PLA(2) using the same carrier to achieve effective gene delivery.
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PMID:Polysaccharide nanogel gene delivery system with endosome-escaping function: Co-delivery of plasmid DNA and phospholipase A2. 2188 55

For the past few years, immunotherapy has recently shown considerable clinical benefit in CRC therapy, and the application of immunologic therapies in cancer treatments continues to increase perennially. Interleukin-12, an ideal candidate for tumor immunotherapy, could activate both innate and adaptive immunities. In this study, we developed a novel gene delivery system with a self-assembly method by MPEG-PLA and DOTAP(DMP) with zeta-potential value of 38.5mV and size of 37.5nm. The supernatant of lymphocytes treated with supernatant from Ct26 transfected pIL12 with DMP could inhibit Ct26 cells growth ex vivo. Treatment of tumor-bearing mice with DMP-pIL12 complex has significantly inhibited tumor growth at both the subcutaneous and peritoneal model in vivo by inhibiting angiogenesis, promoting apoptosis and reducing proliferation. The IL-12 plasmid and DMP complex may be used to treat the colorectal cancer in clinical as a new drug.
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PMID:Modified nanoparticle mediated IL-12 immunogene therapy for colon cancer. 2842 54

Rationale: Colorectal cancer (CRC) is the third most commonly diagnosed cancer around the world. Over the past several years, immunotherapy has demonstrated considerable clinical benefit in CRC therapy, and the number of immunologic therapies for cancer treatment continues to climb each year. Interleukin-15 (IL15), a potent pro-inflammatory cytokine, has emerged as a candidate immunomodulator for the treatment of CRC. Methods: In this study, we developed a novel gene delivery system with a self-assembly method using DOTAP and MPEG-PLA (DMA) to carry pIL15, denoted as DMA-pIL15 which was used to treat tumor-bearing mice. Results: Supernatant from lymphocytes treated with supernatant derived from CT26 cells transfected with DMA-pIL15 inhibited the growth of CT26 cells and induced cell apoptosis in vitro. Treatment of tumor-bearing mice with DMA-pIL15 complex significantly inhibited tumor growth in both subcutaneous and peritoneal models in vivo by inhibiting angiogenesis, promoting apoptosis, and reducing proliferation through activation of the host immune system. Conclusion: The IL-15 plasmid and DMA complex showed promise for treating CRC clinically as an experimental new drug.
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PMID:Powerful anti-colon cancer effect of modified nanoparticle-mediated IL-15 immunogene therapy through activation of the host immune system. 3158 29

Hyper-branched PG6-PLA polymers based on hydrophilic hyperbranched polyglycerol (PG6) and the ester chain poly(l-lactide) (PLA) were synthesized and facilitated to develop a novel biocompatible release-controlled gene vector. The hyper-branched structure of PG6-PLA was verified by NMR, FT-IR and SEC-MALLS analysis. The co-assembly of PG6-PLA with high molecular weight polyethylenimine (PEI) of 25 kDa was discussed. The results of TEM, fluorescence tracking and size/zeta-potential analysis revealed that the PG6-PLA/PEI25k/DNA could co-assemble to generate a novel fiber core-shell conformation. In vitro cell experiment demonstrated that PG6-PLA significantly enhanced the ability of PEI25k to remain within cells and mediate luciferase and EGFP expression in the human embryonic kidney cell line 293T and human cervical carcinoma cell line HeLa, which was accompanied by improved cell biocompatibility and an extended period of transgene expression. Importantly, the binary vector PG6-PLA/PEI25k exhibited specific affinity to some tumour cell lines including HeLa and the HepG2 human hepatoma cell line. These results suggested that the novel gene delivery system based on fiber core-shell PG6-PLA/PEI25k/DNA can serve as a gene delivery system to mediate more efficient transgene expression.
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PMID:Binary gene vectors based on hyperbranched poly(l-lactide-co-polyglycerol) and polyethylenimine for prolonged transgene expression via co-assembly with DNA into fiber core-shell triplexes. 3226