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)

Odontoblasts are involved in tooth repair and regeneration as well as dentin formation. The aim of this study was to examine whether delivery of heat shock protein 27 (Hsp27) into cells using a TAT fusion protein system (TAT-Hsp27) enhances adhesion and migration of murine dental papilla-derived MDPC-23 cells. Hsp27 was delivered into cells by the TAT-fusion protein system. To examine whether TAT-Hsp27 affects the viability of MDPC-23 cells, MTT assay was performed. The effect of TAT-Hsp27 on adhesion and migration of MDPC-23 cells was determined using type I collagen-coated plates and a commercial kit, respectively. In addition, a precise molecular mechanism was examined by Western blot analysis and focal adhesion activity. TAT-fusion protein system delivered Hsp27 into cells successfully. Transduction of TAT-Hsp27 induced adhesion and migration of MDPC-23 cells in a dose-dependent manner. Moreover, transduction of TAT-Hsp27 increased the protein expression of beta1 integrin and focal adhesion formation, and induced phosphorylation of FAK and ERK. TAT-Hsp27-induced migration of MDPC-23 cells was restored by treatment of anti-beta1 integrin antibody. These findings suggest that TAT-Hsp27 promotes adhesion and migration of MDPC-23 cells via beta1 integrin-mediated signaling and is a promising candidate for therapeutic application of dental pulp regeneration.
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PMID:TAT-Hsp27 promotes adhesion and migration of murine dental papilla-derived MDPC-23 cells through beta1 integrin-mediated signaling. 2066 53

Heat shock proteins, acting as molecular chaperones, protect heart muscle from ischemic injury and offer a potential approach to therapy. Here we describe preparation of an injectable form of heat shock protein 27, fused with a protein transduction domain (TAT-HSP27) and contained in a hybrid system of poly(d,l-lactic-co-glycolic acid) microsphere and alginate hydrogel. By varying the porous structure of the microspheres, the release of TAT-HSP27 from the hybrid system was sustained for two weeks in vitro. The hybrid system containing TAT-HSP27 was intramyocardially injected into a murine myocardial infarction model, and its therapeutic effect was evaluated in vivo. The sustained delivery of TAT-HSP27 substantially suppressed apoptosis in the infarcted site, and improved the ejection fraction, end-systolic volume and maximum pressure development in the heart. Local and sustained delivery of anti-apoptotic proteins such as HSP27 using a hybrid system may present a promising approach to the treatment of ischemic diseases.
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PMID:Injectable microsphere/hydrogel hybrid system containing heat shock protein as therapy in a murine myocardial infarction model. 2395 41

Myocardial infarction (MI) results in the substantial loss of functional cardiomyocytes, which frequently leads to intractable heart disorders. Cardiac stem cells (CSCs) that retain the capacity to replace all cardiac cells might be a promising strategy for providing a source of new functional cardiomyocytes; however, the poor survival and engraftment of transplanted CSCs in the hostile environment of MI critically mitigate their therapeutic benefits. To capitalize their therapeutic potential, an ex vivo strategy in which CSCs were introduced to the recombinant heat shock protein 27 (Hsp27) through a TAT protein transduction domain for increasing the viability and engraftment in the infarcted myocardium was designed. A recombinant TAT fused Hsp27 (TAT-Hsp27) was able to enter CSCs in a dose-dependent manner. CSCs transduced with TAT-Hsp27 expressed not only endogenous Hsp27 but externally introduced Hsp27, resulting in substantial increase of their anti-oxidative and anti-apoptotic properties via suppressing reactive oxygen species production, the MAPKs signaling pathway, and caspase activation. TAT-Hsp27 enabled CSCs to be protected from apoptotic- and hypoxic-induced cell death during in vitro cardiomyogenic differentiation. In vivo studies demonstrated that CSCs transduced TAT-Hsp27 significantly increased the survival and engraftment in the acutely infarcted myocardium, which is closely related to caspase activity suppression. Finally, CSCs transduced TAT-Hsp27 improved cardiac function and attenuated cardiac remodeling in comparison with non-transduced CSCs. Overall, our approach, which is based on the ex vivo intracellular transduction of TAT-Hsp27 into CSCs before myocardial delivery, might be effective in treating MI.
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PMID:Intracellular transduction of TAT-Hsp27 fusion protein enhancing cell survival and regeneration capacity of cardiac stem cells in acute myocardial infarction. 2623 24