Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P51532 (transcriptional activator)
 6,546 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Alginate production in mucoid Pseudomonas aeruginosa isolates from cystic fibrosis patients is under direct control by AlgU, the P. aeruginosa equivalent of the extreme heat shock sigma factor sigma(E) in gram-negative bacteria, and AlgR, a response regulator from the superfamily of two-component signal transduction systems. In this report, we describe the identification of the algZ gene, located immediately upstream of algR, which is involved in the control of alginate production. The predicted product of the algZ gene showed similarity to a subset of sensory components from the superfamily of signal transduction systems but lacked several of the highly conserved motifs typical of histidine protein kinases. Inactivation of algZ in the wild-type standard genetic strain PAO1 did not affect its nonmucoid morphology. However, inactivation of algZ in a mucoid mutant P. aeruginosa strain, which had AlgU freed from control by the anti-sigma factor MucA, resulted in increased alginate production under growth conditions which did not permit expression of mucoidy in the parental algZ+ strain. The observed effects were abrogated when algR was inactivated in the algZ::Tc(r) background. These findings indicate that algZ plays a regulatory role in alginate production, possibly interacting with AlgR, and that it may have negative effects on expression of the mucoid phenotype under the conditions tested. The presented results suggest that elements of negative regulation exist at the levels of both the alternative sigma factor AlgU and the transcriptional activator AlgR which, once relieved from that suppression, cooperate to bring about the expression of the alginate system.
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PMID:Identification of the algZ gene upstream of the response regulator algR and its participation in control of alginate production in Pseudomonas aeruginosa. 898 97

Ischemic disease is associated with high mortality and morbidity rates, and therapeutic angiogenesis via systemic or local delivery of protein drugs is one potential approach to treat the disease. In this study, we hypothesized that combined delivery of TAT-HSP27 (HSP27 fused with transcriptional activator) and VEGF could enhance the therapeutic efficacy in an ischemic mouse model, and that sequential release could be critical in therapeutic angiogenesis. Alginate hydrogels containing TAT-HSP27 as an anti-apoptotic agent were prepared, and porous PLGA microspheres loaded with VEGF as an angiogenic agent were incorporated into the hydrogels to prepare microsphere/hydrogel hybrid delivery systems. Sequential in vitro release of TAT-HSP27 and VEGF was achieved by the hybrid systems. TAT-HSP27 was depleted from alginate gels in 7 days, while VEGF was continually released for 28 days. The release rate of VEGF was attenuated by varying the porous structures of PLGA microspheres. Sequential delivery of TAT-HSP27 and VEGF was critical to protect against muscle degeneration and fibrosis, as well as to promote new blood vessel formation in the ischemic site of a mouse model. This approach to controlling the sequential release behaviors of multiple drugs could be useful in the design of novel drug delivery systems for therapeutic angiogenesis.
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PMID:Sequential delivery of TAT-HSP27 and VEGF using microsphere/hydrogel hybrid systems for therapeutic angiogenesis. 2326