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

Summary: The 2006 Nobel Prize in Physiology or Medicine was awarded to two American scientists – Andrew Fire and Craig Mello for the fundamental discoveries in gene expression regulation in eukaryotes. They have shown that the presence of double-stranded RNA in the cell induces specific gene silencing. This phenomenon was called RNA interference – RNAi. Double-stranded RNA is digested in the cell to short effector RNAs, called siRNAs, which are directly responsible for the selective degradation of target mRNA. The process takes place in the cytoplasm. Double-stranded RNA may appear in the cell as a consequence of viral infection or as a product of transcription of retrotransposones or inverted – repeat sequences. The mechanism is present in almost all eukaryotes, and its primary goal was, most probably, the protection of the cell against invasive forms of nucleic acids. Short RNAs have been also found to be encoded by endogenous, eukaryotic genes. Their mode of action closely resembles that of siRNA molecules. They are involved in the regulation of developmental processes and cell responses to environmental changes.

Key words: Nobel prize, RNA interference, micro RNA, gene expression regulation

Summary: Hepcidin is an antimicrobial peptide mainly sythesized in hepatocytes and released into circulation as a prohormone. Recent evidence shows that hepcidin is the hormone regulating of iron homeostasis in the body. The lack of the hepcidin expression results in iron overload and overexpression of the hepcidin has been associated with iron deficiency anemia. The synthesis of the hepcidin is stimulated by high iron diet or inflammation and it is decreased by low iron diet, anemia or hypoxia. Evidence indicates that hepcidin is the negative regulator of iron absorption and iron release from macrophages of the reticuloendothelial system. The relationship between iron and hepcidin is disrupted in patients with hemochromatosis and anemia of chronic disease. The exact understanding the role of the hepcidin could lead to new therapies for disorders of the iron metabolism.

Key words: hepcidin, iron metabolism, anemia of chronic disease, HFE, hemochromatosis

Summary: It is almost 70 years since Mikhail Chailakhyan put forward his hormonal theory of flowering induction, which envisaged the leaves producing and exporting to the shoot apex a specific floral hormone which he called „florigen”. The search for isolation of mythical florigen ended unsuccessfully. However, the investigations have shown that fundamental for flower induction is cooperation between family of flowering gens which express high activity in cells of vascular bundles. The mobile flowering signal could be a product of one of them in the form of transcript mRNA or protein.

Summary: Cyclic adenosine 3’:5’-monophosphate and cyclic guanosine 3’:5’-monophosphate, commonly know as cAMP and cGMP, are key second messengers in living organisms ranging from bacteria to Homo sapiens. Cyclic AMP and cyclic GMP are produced from ATP and GTP by the action of adenylyl cyclase and guanylyl cylase and are hydrolyzed to AMP and GMP by the cyclic nucleotide phosphodiesterase. The natural occurrence of cyclic nucleotides in higher plants is now established, as is the presence of enzymes involved in their metabolism. Accumulating evidence suggests crucial roles for both cyclic nucleotides in plant cellular homeostasis. Here we review the past and recent evidence establishing the presence of these compounds, their metabolism and role in plants.

Summary: b-barrel proteins are present in the outer membrane of Gram-negative bacteria and of organelles of endosymbiotic origin, i.e. mitochondria and chloroplasts where they perform a variety of functions. Mitochondrial b-barrel proteins are important for protein import, metabolite transport and the organelle morphology and distribution. They also seem to play a crucial role in mitochondria evolution. Quite recently a specific pathway for the insertion of b-barrel proteins was identified in both mitochondria and Gram-negative bacteria and was proved to be conserved during evolution. In mitochondria the pathway is formed by the TOB/SAM complex (topogenesis of the mitochondrial outer membrane b-barrel proteins/sorting and assembly machinery) composed of three main proteins, namely Tob55 (Sam50), Tob38 (Sam35) and Mas 37 (Sam37). Phylogenetic analysis provides a strong case for the evolution of Tob55 from the bacterial homologue Omp85 while other mitochondrial b-barrel proteins do not display amino acid homology with bacterial b-barrel proteins.

Key words: mitochondria, biogenesis, evolution, b-barrel, the TOB/SAM complex

Summary: Analysis of fetal cells and cell-free fetal DNA in maternal peripheral blood raises hopes for development of new non-invasive prenatal diagnosis. Many different cell types were considered as possible targets for prenatal diagnosis. Probably, fetal cells and cell-free fetal DNA enter the maternal circulation during all pregnancies. They may persist for years in maternal blood and tissues, resulting in a physiological microchimerism. It has been shown that changes in these two parameters may accompany some pregnancy-related disorders. Microchimerism is associated with pathology of several autoimmune diseases and diseases which preferentially affect women. However, its long-term consequences are still under investigation. Widespread clinical implication of fetal cells and cell-free fetal DNA as diagnostic tools awaits further research aiming at improvement of insufficiently sensitive techniques.

Key words: microchimerism, autoimmune diseases, pregnancy complications, prenatal diagnosis

Summary: Homosporous ferns produce only one type of haploide spores, however each of them is sexually bipotential and can develop as a male or hermaphrodite gametophytes. Their sex is often determined by an epigenetic mechanism that is responsive to antheridiogens which are secreted by hermaphrodites and promote the development of males from sexually undetermined gametophytes. Analyses of sex determination in the gametophytes of Ceratopteris richardii, one of the model fern species, has been defined a hypothetical network of at least eight interacting genes involved in sex expression with connection of endogenous antheridiogen. However, in the gametophytes of Anemia phyllitidis, the second important model system in the studies of sex determination, male sex could be induced by gibberellic acid which imitates the action of antheridic acid, the main antheridiogen of that fern. Gibberellic acid produces specific cytomorphological effects which allowed to create the three zone model of A. phyllitidis gametophyte structure. The results of recent analyses have revealed that ethylene involved in controlling sex determination in A. phyllitidis. It seems to mediate the action of gibberellin in process of sex expression. In this paper the hypothetical mechanism of this activity is proposed.

Key words: Anemia phyllitidis, antheridogens, ethylene, gibberellic acid, sex determination

Summary: Polar auxin transport is essential for normal plant growth and development. Auxin moves between plant cells through a combination of membrane diffusion and carrier-mediated transport. Recent studies have identified several classes of membrane proteins involved in auxin transport, and have started to uncover a system that regulates auxin flux through plant tissues via the subcellular asymmetric localization of these proteins. Localization of auxin transporters is controlled by vesicle-trafficking system, by interactions with protein kinases and phosphatases and by the profile of phospholipids and sterols in cell membrane.

Summary: The human proto-oncogene STAT3 encodes transcriptional factor that is essential for embryogenesis, proliferation and differentiation of many cell types, in addition to organ regeneration and involution. It also regulates innate and adaptive immune mechanisms, including B cell maturation. Augmented STAT3 activation has been found in both irreversibly committed B cell lineage precursors and plasmacytes. Abnormal STAT3-mediated signal transduction has been observed in a large number of neoplasms, in which it induces anti-apoptotic and cell cycle progression mediating genes transcription. In many tumor types, also of lymphoid origin, STAT3 facilitates tumor expansion due to angiogenesis stimulation and attenuation of anti-cancer immunity. STAT3 can be considered as a perfect therapeutic target.

Key words: STAT3 protein, B-lymphocytes, apoptosis, cell proliferation, lymphoma

Summary: Endotoxin (lipopolysaccharide, LPS) of Gram-negative bacteria is the important initiating agent of inflammation. LPS stimulates inflammatory cells, including blood platelets, to production of secondary mediators of inflammation. The uncontrolled development of inflammation is responsible for pathophysiological reactions; leads to sepsis and septic shock and even to death. Blood platelets play an important role not only in haemostasis but also in inflammation and in pathogenesis of septic shock. Activation of blood platelets leads to platelets adhesion, aggregation and secretion of proinflammatory agents. LPS activates blood platelets by inflammatory mediators released from other cells and probably can directly interact with blood platelets. This review presents the role of blood platelets in inflammation and in biological activity of lipopolysaccharide and direct influence of its on blood platelet functions.

Key words: blood platelets, activation of blood platelets, lipopolysaccharide (LPS, endotoxin), infection

The Regulation of Feeding Behavior in Obese fa/fa Zucker Rsts at The Central Nervous System Level – The Role Of Leptin

Summary: The aim of the presented paper is the description of disturbances in the central nervous system (OUN) functions of fa/fa Zucker rats, in which the development of morbid obesity is observed as a result of a defect in leptin functioning. Zucker fa/fa rats possess a defect in a gene, which codes leptin receptor. A single exchange of adenine to cytosine in the 806th position of extracellular domain of the receptor results in coding proline instead of glutamine (Gln269Pro). Due to point mutation, the regulation of food intake in fa/fa rats is drastically changed, probably caused by the lack of the leptin receptor and/or leptin protein in the OUN. As a consequence, the deregulation of energetic homeostasis and a dramatic increase of body mass are observed. In spite of the high level of leptin in the blood, these animals are resistant to the circulating hormone, which under regular conditions reaches the brain decreasing food intake and enhancing the energy metabolism. The involvement of leptin in the regulation of food intake comprises interactions with several hormonal systems in the CNS. In the presented rewiev we have shown that the lack of the functional leptin receptors have impact on synthesis of several mediators in the brain. Abnormalities in gene expression and/or protein levels of neuropeptide Y, orexin, CART peptide, or AgRP were observed in the brain of the rats. Additionally, lower concentration of insulin and its receptors have been also noted in the brain of fa/fa rats. Disrupted leptin function may also lead to an impairment of the system reacting to glucose in the brain. It has been shown that the brain of obese Zucker rat contains significantly reduced number of glucose-sensitive neurons and glucose ultilization was markedly diminished in distinct hypothalamic regions. However, the presented data are only a part of a complicated and partially explained mechanisms regulating feeding behavior in fa/fa rats.

Key words: neuropeptide Y, orexin, CART peptide, leptin, insulin, glucose-sensitive neurons

Summary: Phytoestrogens are biological active substances present in many plants. Phytoestrogens, mycoestrogens and xenoestrogens belong to so called environmental estrogens which may affect different biochemical processes in animals. In the review we attempt to present current knowledge on classification and occurrence of phytoestrogens as well as their metabolism and biological effects in females.

Key words: phytoestrogens, genistein, daidzein, metabolism, reproductive processes, steroidogenesis, breast cancer, osteoporosis, menopause, vascular disease, female

Phytoestrogens. II. Molecular Mechanism of Action In Female Reproductive Tract

Summary: Phytoestrogens are plant-derived chemical compounds which may affect reproductive processes in humans and animals. In their target cells, phytoestrogens may mimic (estrogenic effects) or antagonize (antiestrogenic effects) action of endogenous estrogens. In the current paper, contemporary views are presented on intracellular mechanism of phytoestrogen action in ovarian, uterine, and mammary gland cells.

Key words: phytoestrogens, genistein, daidzein, signal transduction, estrogen receptors, estrogenic effect, antiestrogenic effect, female