Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.3.1.108 (TAT)
 2,389 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Viral entry through the blood-brain barrier (BBB) has not been fully defined and identification of coreceptors that can facilitate this phenomenon is crucial in understanding disease progression. Using a RNAse protection assay to examine chemokine receptor families simultaneously, we analyzed the total RNA of in vitro BBB cultures treated with purified preparations of HIV gp120, gp41, TAT proteins and TNF-alpha. HIV tat protein affected CCRI and CCR3 mRNA expression whereas the other viral by-products had no effect. Interestingly, TNF-alpha was able to induce CCR1, CCR3 as well as CXCR1, CXCR2, CXCR4 receptors and Burkitt's lymphoma receptor BLR2. These results suggest that HIV-induced molecules can manipulate the surface receptor expression of the BBB to allow for their preferential entry into brain.
 ...
PMID:Chemokine receptor mRNA expression at the in vitro blood-brain barrier during HIV infection. 1009 32

The chemokine receptor, CXCR4, and its specific ligand, CXCL12, have been proven to regulate the directional trafficking and invasion of breast cancer cells to sites of metastases, and similar phenomena have also been identified in many malignant tumors that aberrantly overexpress CXCR4. Therefore, blocking the interaction between CXCR4 and CXCL12 is considered a possible approach to efficiently prevent cancer metastasis. Employing a cellular phenotypic knockout strategy based on intrakines, we developed a novel recombinant chimeric protein, TAT/54R/KDEL, which contains three distinct functional domains: CXCL12/54R, a mutant of CXCL12 with CXCR4 antagonism, as well as HIV-derived TAT (47-57) and an endoplasmic reticulum retention four-peptide sequence KDEL that links at its NH(2) and COOH termini, respectively. Using the MOLT-4 cell line, which expressed CXCR4 highly and stably in vitro, we determined that TAT/54R/KDEL was able to efficiently transfer into the endoplasmic reticulum of tumor cells, where it specifically binds to the newly synthesized CXCR4 and prevents the latter from reaching the surface. Chemotaxis assays showed that the cells treated with TAT/54R/KDEL failed to migrate toward CXCL12. Furthermore, we observed that the systemic treatment of TAT/54R/KDEL could impair lung metastasis in a highly metastatic mammary cancer cell line, 4T1 cells, with the decrease of CXCR4 on their membrane. Our results suggest that the phenotypic knockout strategy of CXCR4 using a novel recombinant protein TAT/54R/KDEL might be a possible approach for inhibiting relative tumor metastasis mediated by CXCR4/CXCL12 interaction.
 ...
PMID:Phenotypic knockout of CXCR4 by a novel recombinant protein TAT/54R/KDEL inhibits tumors metastasis. 1982 96

Early brain injury (EBI) after aneurysmal subarachnoid hemorrhage (SAH) contributes to high morbidity and mortality. Although it is well recognized that acute neuroinflammation reaction is one of the most important triggers of EBI, pharmacotherapy proved to be clinically effective against the initiating of neuroinflammation after SAH is lacking. The resident microglia and infiltrated peripheral monocyte are two main types of immune cells in central nervous system (CNS) and control the inflammation process in brain after SAH. But the time course and relative contributions of these two immune cell activations after SAH are unknown. The p75 neurotrophin receptor (p75NTR), member of TNF receptor superfamily, expresses on infiltrated peripheral monocytes and suppresses their proinflammatory action after brain insults. But the p75NTR expression on resident microglia in vivo is rarely explored and their function keeps elusive. Therefore, we designed this study to investigate the time course of resident microglia activation and peripheral monocyte infiltration, as well as the microglial expression of p75NTR by using CX3C-chemokine receptor 1 (Cx3cr1) and chemokine receptor 2 (Ccr2) double transgenic mice (Cx3cr1GFP/+Ccr2RFP/+) after SAH. The results showed activated microglia was observed in cortex as early as 24 h and further increased at 48 and 72 h post SAH, while the infiltrated monocyte was not found until 72h. In addition, activated microglia expressed p75NTR acutely and p75NTR specific antagonist TAT-Pep5 significantly reduced microglia activation, neuroinflammation and EBI from 24 to 72 h. Together, these data suggest that the early neuroinflammation reaction might be initiated and intensified mainly by resident microglia rather than infiltrated monocyte at least in the first 48 h after SAH and p75NTR blockading by TAT-Pep5P might alleviate EBI through mediating microglial activation.
 ...
PMID:Resident Microglia Activate before Peripheral Monocyte Infiltration and p75NTR Blockade Reduces Microglial Activation and Early Brain Injury after Subarachnoid Hemorrhage. 3011 29