Postepy Biologii Komorki, vol. 32, 2005, issue 1

Summary: Nitric oxide (NO) is an inorganic free radical, that plays an important role in regulation of variety processes in living organisms. Soils are an important source of NO, produced during denitrification, nitrification and reduction of NO₃^- to NH₄⁺. In plants NO production depends on the activity of nitric oxide synthase and/or nitrate reductase as well as non enzymatic generation of NO can be detected. Similarly as in animals, in plant cells NO is widely regarded as a signaling molecule. There are a number of data proving that different NO donors (sodium nitroprusside, S-nitrosoglutathione, S-nitroso-N-acetyl-D-penicillamine) stimulate seed germination of many plants. Moreover endogenous synthesis of NO during seed germination was reported, indicating its role as a link to activation of embryonic axes. Although it is not questionable that NO acts as mediator of seed germination its mode of action in this process is still known only fragmentary. NO stimulates germination of photoblastic seeds, by activation of phytochrome signal transduction pathway. On the other hand NO interact with classical phytohormones (ethylene, abscisic acid, gibberellins) involved in regulation of seed germination.

Key words: germination, nitric oxide, phytochrome, plant hormones, seed dormancy

Summary: Chloroplasts of higher plants contain thylakoid membranes differentiated into several cylindrical granum stacks of appressed (stacked) membrane which are surrounded by non-appressed (unstacked) helically organized stroma thylakoids. The light reactions of photosynthesis are mediated by chlorophyll-protein complexes – Photosystem I (PSI) and Photosystem II (PSII) differentially embedded in granum and stroma membranes. Moreover, electron transport and conversion of light energy into ATP depend on cytochromes b₆f and ATP synthase complexes. The photosystem core complexes are organized into large protein-pigment complexes with specific peripheral antennae, chlorophyll-binding light-harvesting complexes, LHCI and LHCII. Trimeric, mobile LHCII antenna and LHCII-PSII supercomplexes build up microdomain structure or megacomplexes, which determine the thylakoid structure. Furthemore, the flexible mechanisms of photosynthesis in response to environmental factors are closely related to rearrangement of supercomplexes in thylakoid membranes.

Key words: chloroplasts, thylakoid membranes, chlorophyll-protein complexes, PSI, PSII, LHCII, supercomplexes, structural arrangements

Summary: Receptor (RTK) and nonreceptor (NTK) protein tyrosine kinases play a central role in transduction of extracellular signals, both in normal and neoplastic cells. Therefore, several approaches to inhibit PTKs have been developed. According to the structure of natural protein kinase inhibitors (quercetin, erbstatin ) Levitzki and coworkers prepared first synthetic tyrosine kinase inhibitors and coined the term „tyrphostins” (tyrosine phosphorylation inhibitors). Over 30 tyrphostins are now in various stages of clinical development. The structure, biological properties and antitumor activity of selected receptor tyrosine kinase inhibitors (EGFRs, IGFRs, VEGFRs) and nonreceptor kinase BRC-ABL are discussed. The recent results indicate, that most effective therapy may be administration of the combination of PTK inhibitors with other signal transduction inhibitors or cytostatics.

Summary: Osteoporosis is a chronic systemic disease characterized by progressive loss of bone mass and microarchitectural deterioration of bone tissue. Bone lesions are caused by different factors, including hereditary ones. A process named bone remodeling is the effect of balanced osteoclastogenesis and osteoblastogenesis, two primary processes controlled by a number of proteins. The osteoclasts proliferation and differentiation are regulated by: PU.1, MITF, M-CSF, c-Src, PI-3K, c-Fms, RANK, NFATc1, NFkB and cFos/Fra-1 proteins. Activation of bone resorption during remodeling depends on the direct interaction of osteoblasts and osteoclasts. Osteoblast cell surface protein RANK interacts with its ligandRANKL – the cytokine secreted by osteoblasts. Despite that, Wnt signalling pathway proteins and their coreceptors – LRP-5 and LRP-6 proteins, are involved in regulation of osteoblast function. Over 3 decades passed since identification of genes/alleles responsible for osteoporosis phenotype. The most intensively studied genes up to now are VDR, COLIA1 and ER. Genes involved were invented as four groups of biological factors: cytokines, growth factors, bone matrix proteins and calciotropic hormones and receptors. Type I collagen is a fibrillar protein, the main constituent of bone matrix, VDR is cytoplasmic vitamin D receptor as well as ER, estrogen receptor, which regulates expression of target genes involved in bone homeostasis. The correlation between particular LRP-5 alleles and function of transmembrane LRP-5 protein is not clear, however it is suggested that polymorphisms of LRP-5 gene may contribute to BMD alterations, thus influencing the risk of developing osteoporosis. Besides allelic variants of TGFb-1 gene, a number of mutations of proinflammatory cytokines IL-1 and IL-6 genes exist, of which translation products correlates with the level of estrogens in women which in turn may influence osteoporotic pathophysiology. Among sequence alterations analised are polymorphic restriction sites BsmI, ApaI, EcoRV, FokI and TaqI of VDR gene and their association with femoral-neck and total skeleton BMD. Researchers are particularly interested in polymorphism at Sp1 binding site in COLIA1 gene, which is suggested to be a genetic marker of microarchitectural bone deterioration. Moreover, there are a number of polymorphisms associated with osteoporotic phenotype i.e. BstI, PvuII i XbaI in ERa gene, PvuII in CD38 gene as well as others in OSCAR and RUNX2 genes. Despite a huge number of data on genetic background of osteoporosis, there are still many discrepancies. However genetic research on osteoporosis will surely lead to unequivocal identification of molecular markers which could be finally useful for diagnostic and therapeutic purposes.

Key words: osteoporosis, BMD, bone remodeling, COLIA1, VDR, ER, LRP-5, RUNX2

Summary: Mammalian target of rapamycin (mTOR) is a serine-threonine protein kinase that regulates rate of several intracellular processes in response to extracellular signals, nutrients availability and energy status of the cell. mTOR regulates survival, differentiation and development of neurons including processes such as development of axon and dendritic arbor and synaptogenesis. In adult brain mTOR is crucial for synaptic plasticity as well as for learning and memory formation. Recent studies show that inappropriate activation of mTOR might be linked to several pathologies of the nervous system including brain tumors and neurodegenerative disorders such as Alzheimer`s, Parkinson`s and Huntington`s diseases. This review presents current knowledge about a role of mTOR in physiology and pathology of the nervous system.

Key words: mTOR kinase, differentiation of neurons, tumors, neurodegenerative disorders

Key words: plant cell, polyamines, transglutaminases, polyamine mutants, transgenic plant

Summary: Current ideas concerning various aspects of the biology of dendritic cells (DC) were presented, including subdivision on two subsets and follow-ups of their activation. The issue of DC cross-presentation (cross-priming) was discussed in detail as an important facet of their immunobiological function. The relevant role of DC in immunoregulation was underlined, particularly the action of immunosuppressive cytokines such as IL-10 and TGF-b and the enzyme indoleamine 2,3-dioxygenase (IDO). Attention was paid to the significance of DC in the induction of immunological tolerance. Evidence was presented for the existence of NK cells with functional and phenotypic features of dendritic cells and at the same time showing cytotoxic properties. In the next section examples of participation of DC in various human diseases were provided including infectious diseases, autoimmunity and immunodeficiencies. Attention was paid to a separate population of follicular dendritic cells, residing in lymphatic nodules of lymph nodes and their role in multiplication of infectious agents active in transmissible spongiform encephalopathies. In the final section new perspectives of vaccine production were indicated based on the application of DC linked to biopolymers such as liposomes, nanoparticles and others.

Keywords: Dendritic cells, cross presentation, immunoregulation, the role in human pathology

Summary: VEGF-A is a glycoprotein, which belongs to the vascular endothelial growth factor family. The human VEGF-A gene is composed of 8 exons, separated by 7 introns and is localized in chromosome 6p21.3. Alternative exon splicing of a single VEGF gene results in the generation of the ten different isoforms known as 121, 138, 145, 148, 162, 162b, 165, 183, 189 and 206. VEGF-A binds to two tyrosine kinase receptors Flt-1 and Flk-1. Activation of the receptors leads to a rapid recruitment of the adaptor proteins Shc, Grb2, Nic, Nck, Crk, protein tyrosine phosphatases SHP-1 and SHP-2 as well as Akt/PKB serine/threonine kinase, phospholipase Cc(PLCc), focal adhesion kinase FAK and PI-3 kinase. Oxygen tension is a key regulator of VEGF gene expression. Hypoxia-inducible transcription of VEGF is mediated, at least in part, by the binding of hypoxia-inducible factor 1 HIF-1 to an HIF-1 binding site located in the VEGF promoter. VEGF-A plays very important roles in the organism of which angiogenesis is the most significant. The understanding of the mechanisms of angiogenesis can create the basis of new methods of treatment of some diseases with accompanying angiogenesis disturbances, such as antiangiogenic cancer therapy, and therapeutic angiogenesis in case of cardiac, brain and limb ischemia.

Key words: vascular endothelial growth factor – VEGF-A, Flt-1 and Flk-1 receptors, HIF-1 transcription factor, signal transduction, antiangiogenic therapy

Summary: Natural exogenous immunostimulators are preparations isolated from bacteria, plants or fungi that activate immunological system. Present research is aimed at understanding the exact mechanism of their action and improving their efficacy in parallel with reducing minor side effects. It appears that in the majority therapeutical effects of the bacterial and fungal preparations result from the activation of Toll-like receptors (TLR). However, biologically active substances isolated from plants can activate cells through non-specific interaction with their surface. In the present work, the most important biologically active compounds were discussed: bacterial – BCG, LPS; isolated from plants – purple coneflower (Echinacea spp.), mistletoe (Viscum album); and fungal – lentinan, schizophyllan, krestin. The mode of their actions with both the present and potential therapeutic applications were discussed. Among groups mentioned above, the most commonly used in medicine are BCG and purple coneflower preparations. BCG is applied in the treatment of superficial bladder cancer. Anticancer effect of BCG results from either eliciting local inflammation or cross-reaction of antibodies specific for BCG with bladder tumor cells. As far as purple coneflower and biologically active substances isolated from the plant are concerned, they have immunostimulating properties because of their effect on non-specific immune response and can act in the antiseptic and antiinflammatory way. The immunostimulating properties of other preparations are generally low. The preparations can be used occasionally as a supplement of the conventional therapy.