Disease relevance of TMSB4X

• In vitro, thymosin beta4 sulfoxide inhibited neutrophil chemotaxis, and in vivo, the oxidized peptide, but not the native form, was a potent inhibitor of carrageenin-induced edema in the mouse paw [1].

High impact information on TMSB4X

• Here we show that thymosin beta4 sulfoxide is generated by monocytes in the presence of glucocorticoids and acts as a signal to inhibit an inflammatory response [1].
• The kinetics of bovine spleen T beta 4 binding to muscle pyrenyl G-actin are sufficiently rapid to accommodate the rapid changes in actin polymerization and depolymerization observed in vivo in response to chemoattractant addition and removal [2].
• On non-denaturing polyacrylamide gels, a large fraction of G-actin in supernatants prepared from resting PMNs has a mobility similar to the G-actin/T beta 4 complex [2].
• The similarity in structures of thymosin beta 4 and thymosin beta 9 suggests that they may have related functions [3].
• Thymosins beta 8 and beta 9: two new peptides isolated from calf thymus homologous to thymosin beta 4 [3].

Biological context of TMSB4X

• Complete amino acid sequence of bovine thymosin beta 4: a thymic hormone that induces terminal deoxynucleotidyl transferase activity in thymocyte populations [4].
• Binding sites of actin and thymosin beta 4 were investigated using a set of bifunctional thiol-specific reagents, which allowed the insertion of cross-linkers of defined lengths between cysteine residues of the complexed proteins [5].
• It is proposed that thymosin beta 4 is one of the biologically active peptides present in thymosin fractions 5 and 5A which participate in the regulation, differentiation, and function of thymus-derived lymphocytes and may also act directly or indirectly on macrophages and perhaps other cells involved in cell-mediated immunity [6].
• The peptides thymosin alpha1 (T alpha1), thymosin beta4 (T beta4), MB35, and MB40 had no effect on either MMQ or C6 cell proliferation, indicating that these TF5 components are not the principle active peptides [7].
• In addition to the main compound thymosin beta 4, bovine tissue contains a related peptide, thymosin beta 9 (T beta 9), which has 41 amino acid residues and ca. 75% sequence homology [8].

Anatomical context of TMSB4X

• The amino acid sequence of thymosin beta 4, a polypeptide isolated from calf thymus, was determined [4].
• Thus, it appears that thymosin beta 4 acts on lymphoid stem cells and may control the early stages of the maturation process of thymus-dependent lymphocytes [4].
• AcSDKP and T beta 4 were both detected in bone marrow cells (BMC) [9].
• Involvement of thymosin beta 4 and endoproteinase Asp-N in the biosynthesis of the tetrapeptide AcSerAspLysPro a regulator of the hematopoietic system [9].
• Brain, kidney, liver and testis contain only 10 to 20% the concentration of thymosin beta 4 seen in spleen, whereas heart and muscle contain only 5 to 10% that of spleen [10].

Associations of TMSB4X with chemical compounds

• Model enzymatic degradation of T beta 4 carried out with bacterial enzymes suggests that a mammalian endoproteinase Asp-N might be involved in the formation of AcSDKP through the specific cleavage of the 4Pro-5 Asp peptide bond of T beta 4 [9].
• Thymosin beta 4 sulfoxide is an anti-inflammatory agent generated by monocytes in the presence of glucocorticoids [1].
• The NH2 terminus of thymosin beta 8 is acetylalanine, compared with acetylserine in thymosin beta 4 [3].
• The importance of the amino acids 17 and 28 in thymosin beta 4 for the interaction with actin was emphasized by the finding that thymosin analogs containing cysteine in these positions exhibited strongly reduced abilities to inhibit actin polymerization [5].
• Thymosin beta 4 is composed of 43 amino acid residues with acetylserine at the NH2 terminus [6].

Physical interactions of TMSB4X

• The resulting profilin II-peptide complex overcomes the combined capacity of thymosin beta4 and profilin II to inhibit actin nucleation and restores the extent of filament formation [11].
• While the apparent dissociation constant of the actin/thymosin beta 4 complex generated from a preformed actin/DNase-I complex is 160 microM, a fivefold excess of DNase I over the preformed actin/thymosin-beta 4 complex is necessary to observe a comparable dissociation constant [12].

Regulatory relationships of TMSB4X

• On the other hand, antibodies raised against the native thymosin beta 9 (1-14) cross-react 35% with thymosin beta 4 [13].

Other interactions of TMSB4X

• Effects of profilin and thymosin beta4 on the critical concentration of actin demonstrated in vitro and in cell extracts with a novel direct assay [14].
• The effect of thymosin beta4 on articular cartilage chondrocyte matrix metalloproteinase expression [15].

Analytical, diagnostic and therapeutic context of TMSB4X

• Thymosin beta 4 antibodies have been raised in rabbits by conjugating the peptide to keyhole limpet hemocyanin, and a radioimmunoassay for thymosin beta 4 has been established utilizing tritiated thymosin beta 4 as binding ligand [10].
• Fluorescence titration employing pyrenyl-actin in complex with deoxyribonuclease I (DNase I) or thymosin beta4 demonstrated S1 binding to these actin complexes [16].
• To study the influence of paraquat binding to G-actin on the interaction of G-actin with thymosin beta4 we determined the apparent dissociation constant of the G-actin-thymosin beta4 complex in the absence or presence of paraquat using an ultrafiltration assay [17].
• However, on analysis by sedimentation equilibrium ultracentrifugation, prothymosin alpha and thymosin beta 4 showed relative molecular masses of 12,800 and 4600, which are close to the values calculated from their amino acid sequences, confirming their existence in solution as discrete monomeric entities [18].
• First, no additional steps--as for example desalting--are necessary prior to HPLC and thus the risk of losing thymosin beta 4 is eliminated [19].

References