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EN
Nuclear factor kB (NF-kB) is common proinflammatory transcription factor involved in expression of c.a. 300 different genes. It is usually present in the cytosol as an inactive complex and upon activation translocates into the nucleus. The mechanisms of activation of NF-kB are complex and they involve several different signaling pathways and plethora of proteins. In this minireview we describe the main deciphered as well as suggested mechanisms regulating of NF-kB activity
EN
Cyclic GMP is a key messenger molecule in several cellular processes. It is also an important modulator of immune response. In this paper we summarize current data concerning regulatory and modulatory function of cGMP in the cells of immune system. Metabolism of the nucletide as well as its role in processes such as cell proliferation, differentation, chemotaxis and release of mediators are described. The fields of future research are indicated as well.
EN
Cyclic GMP is common second messenger in a plethora of processes. Its major intracellular receptors are the cGMP-dependent protein kinases (PKGs). In this minireview we summarise the main results of studies on structure and physiological role of PKGs.
EN
Phosphodiesterases of cyclic nucleotides (PDEs) are enzymes hydrolyzing cGMP, cAMP or both and are regulated in several different ways. In this paper we summarize current data on structure, cellular and tissue localization, regulation and function of different PDE families that hydrolyze cGMP.
EN
Numerous reports indicate that cyclic 3',5' guanosine monophosphate (cGMP) is involved in the regulation of immune processes. However, the mechanisms responsible for the synthesis of this nucleotide and its signaling pathways in immune cells are still not well recognized. The aim of our study was to establish: 1) which form of guanylyl cyclase synthesizes cGMP in murine lymphoid organs and 2) whether the same organs express the isoforms PKG1alpha and/or PKG1beta of protein kinase G, known as a possible target for synthesized cGMP. Cells isolated from thymus, lymph nodes, and spleen were treated with activators (SNP, ANP, CNP, STa) of soluble or particulate cyclases. Sodium nitroprusside (SNP) elevated intracellular cGMP 2-fold in thymic and lymph node cells and about 10-fold in spleen cells. Atrial natriuretic peptide (ANP) caused modest but statistically significant increases of cGMP in cells of all the organs. Additionally, spleen cells elevated their cGMP content about 2-fold in response to C-type natriuretic protein (CNP). In cellular homogenates of all the analyzed organs, the antibody anti-PKG1beta stained the 78 kDa band corresponding to the molecular mass of PKG1. Only homogenates of spleen cells were stained by the antibody recognizing PKG1alpha. Our results indicate that in all the investigated organs, cGMP may be synthesized mainly by soluble guanylyl cyclases in response to nitric oxide. The modest increase of cGMP upon stimulation by ANP suggests that in all these organs either exist only a small subpopulation of cells that express particulate cyclase GC-A or GC-A is expressed at very low level. In spleen cells, however, cyclase GC-B appears to be the more active enzyme. Elevated cGMP concentration may in turn activate PKG1beta in thymus, lymph node, and spleen cells and also PKG1alpha in spleen cells.
EN
Introduction: Cancer-associated retinopathy (CAR) is a paraneoplastic neurological syndrome resulting in progressive loss of vision and clinical signs of retinal degeneration. It is associated with various types of cancer and is also considered to be an autoimmune disorder that involves cross-reaction between autoantibodies and retinal proteins. The aim of this study was to establish whether immunoreactivity to retinal antigens (RAs) observed in patients with breast cancer is accompanied by any visual impairments. Materials and Methods: Sera of 295 patients with diagnosed breast cancer were screened for the presence of anti-RAs antibodies using immunoblotting. Cellular immunoreactivity to RAs present in retinal extracts and to purified recoverin and arrestin was determined by means of a lymphocyte proliferation assay. Six patients with high-titer antibodies to RAs then underwent ophthalmic and neurological examinations. Results: Four serum samples contained high-titer antibodies to a 46-kDa protein, most probably retinal ?-enolase, three had antibodies to a 48-kDa protein identified as retinal arrestin, while 56-, 43-, 41-, and 34-kDa antigens were recognized only by one serum sample each. Moreover, weak cellular response to all the RAs tested was observed in one patient and another patient responded only to retinal extract. Two of the examined patients displayed symptoms of CAR. Conclusions: Immunoreactivity to RAs in patients with breast cancer may also be present in cases without clinical signs of CAR.
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