We investigated the metabolism of mouse isolated heart under the influence of tricarbonyldichlorothenium (II)- dimer (CORM-2 and 2,3-4,5-bis-O-isopropylidene-βD-fructopyranose sulfamate (topiramate) as potential blockers of aquaporine channel (AQP3) of cardiac myocytes. The results were compared with those obtained from the group receiving anti-AQP3 monoclonal antibodies. A decrease in coronary flow was found during the period preceding ischemia (topiramate did not cause this effect). However, at the end of reperfusion, CORM-2 was responsible for its stabilization. This compound did not affect glucose intake (topiramate increased it only at the end of reperfusion), decreased Ca2+ deposition in cardiac muscle (AQP3-IgG antibodies and topiramate had similar effect), decreased creatinine release, AST (especially at the end of reperfusion). The action of CORM-2 increased the amplitude of the R waveform before ischemia and during reperfusion. At the end of reperfusion the R-wave amplitude decreased. The effect of topiramate caused an increase in amplitude only at the beginning of reperfusion. Administration of CORM-2, topiramate and antibodies resulted in prolongation of the interval before and during ischemia. At the same time, the effect of these drugs and antibodies reduced the development of ischemic damage. The results indicate that the released CO from CORM-2 has effects similar to those of anti-AQP3 antibodies. The action of topiramate had signs of calcium channel blocking.
TNF-receptor-associated factor 3, or TRAF3, is an adapter protein that serves as a potent negative regulator in many aspects of B cell function. Studies in transformed cell lines have shown that TRAF3 can inhibit signaling via the identified CD40 receptor. Due to the fact that the canonical site of TRAF3 on many receptors also mediates the binding of other TRAFs, and TRAF3 deficiency in laboratory mice causes death immediately after birth, a clear understanding of the specific functions of TRAF3 was unknown for a long time. After obtaining partially TRAF3-deficient mice, the search for the functions of this protein continued. The study of TRAF3-deficient B cells in mice and malignant B cells showed that TRAF3 performed important regulatory functions that were unique to this protein. These include suppression of signaling by plasma membrane receptors, downregulation of intracellular receptors, and restriction of the NF-κB cytoplasmic pathways. It is known that TRAF3 regulates signaling from Toll-like receptors in B cells, acting on a number of sequential events, including the production of cytokines. However, the involvement of TRAF3-dependent cytokines in signal regulation induced by receptors for such cytokines is less studied, especially for B cells. TRAF3 also acts as a resident nuclear protein and affects the metabolism of B cells. Through these and additional mechanisms, TRAF3 is able to influence lifespan and the strength of B cell activation. Therefore, it is not surprising that TRAF3 was found to be an anticancer agent in B cells. TRAF3 in B cells appears to have an inhibitory function, thereby affecting glucose metabolism. TRAF3-deficient B cells express increased levels of the glucose transporter Glut1 and the glycolytic enzyme hexokinase 2. This is associated with the frequent loss of TRAF3 function when B cells are converted to malignant cells. This phenomenon can be further used as a marker of a malignant process, which requires further research. Conclusion. Among the various aspects of the TRAF3 study, the relationship between TRAF3 and the various phosphatase enzymes of B and T lymphocytes is important. Intracellular signals in lymphocytes, their mechanisms and biological consequences in case of interaction with both cytokine receptors and TCR are significant. Further research will focus on identifying additional regulatory pathways for TRAF3 as a promoter of ubiquitination, the involvement of cytokine receptors, and TCR signaling, which are discussed in this review
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