In Memoriam:  Professor Mirosław Mossakowski -  A Neurobiologist with Intuition and Vision

Summary: The present paper is devoted to the scientific achievements of Professor Mirosław Mossakowski, a leading figure in neuropathology and neuroscience who passed away a year ago. Professor Mossakowski was Director of the Medical Research Centre of the Polish Academy of Sciences for more than a quarter of a century, and held the post of a President of the Academy from 1998 until his last days. Facts from his professional life are presented in the context of the up-to-date state of the art of the areas of his interest and of the achievements of his scholars, and painted with the authors' experiences derived from the personal contacts with his mentor. The treatise is aimed at documenting Prof. Mossakowski's extraordinary intuition in various areas of neurobiology, in particular his gift to foresee the future lines of research on the physiology and pathology of the central nervous system.

Key words: brain; astrocytes; ischemia; hypoxia; hepatic encephalopathy; protein biosynthesis.
 

The Role of STAT5 Proteins in Hematologic Diseases

Summary: The STAT proteins (signal transducers and activators of transcription) belong to a group of proteins that take part in transducing an extracellular signal from the cell surface into the nucleus. They are activated by binding cytokines, growth factors and hormones to their receptor. Seven STAT proteins are identified up to now: STAT 1, 2, 3, 4, 5a/b and 6. They have proved to play an important role in many of the physiopathological processes related to the immune responses, cell growth, cell cycle regulation and cell transformation. Many studies show that alterations in the JAK-STAT pathway are associated with hematologic diseases. In the present study we discuss structure, functioning and means of inactivation of the STAT protein. Moreover we have presented the latest information about the role that STAT5 proteins plays in hematopoesis, hematooncologic diseases and functions of immunologic system.

Key words: STAT5, JAK, hematopoiesis, hematooncologic diseases.
 

The Role of cGMP in Signal Transduction Pathways In Plant Cells

Summary:Cyclic GMP is a one of the key secondary messengers, acting in many signal transduction pathways in animals. Studies on cGMP role in plant cells last only a decade and indicate that it is a significant element in plant signal transduction system. It was shown that cGMP is involved in the mechanism of defense signaling pathway of HR, phytochrome signal transduction pathway and in the modulation of guard cell system in plants. Similarly as in animals, NO and natriuretic peptides seem to be inducers of cGMP signal in plants too. Despite of many known animal guanylate cyclases, no cGMP generating system was identified in plants till now.

Key words:cyclic GMP, guanylate cyclase, nitric oxide, plants
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The Role of Hepatic Stellate Cells in the Regulation of Liver Functions. I. Morphology and Characteristics of Intact and Cultured Cells

Summary: Hepatic stellate cells (synonyms: vitamin A-storing cells, lipocytes, Ito cells, fat-storing cells, liver-specific pericytes, perisinusoidal cells) are localized in the perisinusoidal space of Disse. They are characterized by the abundance of intracytoplasmic fat droplets (up to 20% of the cell volume), and the presence of well-branched cytoplasmic processes, that embrace endothelial cells and provide focally a double lining for sinusoid. In the normal liver stellate cells store 70-80% of body's vitamin A and control synthesis and turnover of main extracellular matrix components. Due to the presence of smooth muscle (-actin, synthesis of vasoactive compounds, and sensitivity to vasoactive agents, stellate cells regulate contractility of sinusoids, and thus sinusoidal blood flow. Cultured HSC spontaneously transform into metabolically active myofibroblast-like cells that lose lipid droplets, proliferate, migrate and produce enhanced amounts of extracellular matrix components, cytokines, growth factors and many other substances. Hepatocyte damage leads to the activation of quiescent stellate cells that acquire myobibroblast-like phenotype and play a key role in the development of fibrotic response in the liver.

Key words: hepatic stellate cells; morphology; functions; activation.
 

The Role of Hepatic Stellate Cells in the Regulation of Liver Functions. II. Cooperation with Other Cell Types in the Development of Liver Fibrosis

Summary: Hepatic stellate cells play a key role in the initiation and progression of liver fibrosis that is characterized by profound changes in the amount and distribution of the extracellular matrix (ECM). Various mediators released from damaged hepatocytes and activated liver macrophages, sinusoidal endothelial cells, infiltrating leukocytes, and platelets activate quiescent, vitamin A-rich stellate cells into myofibroblast-like cells. The activated or transformed stellate cells lose lipid droplets, proliferate, migrate, contract and synthesize large amounts of ECM components. PDGF and TGF-( represent, respectively, the most mitogenic  and profibrogenic cytokines that act on stellate cells. However, many other substances derived from various liver cell types increase secretory activity of stellate cells that results in excessive ECM accummulation. The early stages of liver fibrosis may be reversible due to the apoptosis-related death of activated stellate cells, their reversal to the quiescent phenotype, and activation of matrix metaloproteinases. Blocking of some signal transduction pathways involved in the profibrogenic activity of stellate cells may provide new ways for the more effective therapy of liver fibrosis.

Key words: hepatic stellate cells, liver fibrosis, cellular cross-talk.
 

RNA Silencing as a  Plant Innate System Against Viral Infection
 

Summary:  RNA silencing is a newly discovered mechanism of gene regulation and defence against viruses. The mechanism is based on sequence-specific targeting and degradation of RNA. It appears to be directed by double-stranded RNA, associated with the production of short 21 to 25 nt RNAs, and spread through the plant by a mobile signal. It is not know what is the signal. Many of plant viruses encode suppressors of RNA silencing, which inhibits of an antiviral defence system in plants. RNA silencing is conceptually similar to classical humoral immunity.

Key words:  viral resistance, RNA silencing, RNA interference, cross protection, post-transcriptional gene silencing, co-suppression.

Mono- and Disacharides - Signaling Molecules Regulating Genes Expression in Yeast, Plant and Animal Cells

Summary: Some mono- and disaccharides act as signaling molecules that control gene expression. In the yeast, two transporter-like proteins (Snf3, Rgt2) have been shown to function as glucose sensor in a pathway for glucose induction of transporter genes. Another G-protein coupled receptor Gpr1 activates signaling pathway containing adenylate cyclase and protein kinase A. Results of many investigations suggest that in yeast cells a hexokinase plays important role in sensing endogenous levels of glucose. A central component of the sugars signaling pathways is SNF1 protein complex. This high molecular mass complex contains Snf1 protein kinase, Snf4 protein and bridging protein (Sip1, Sip2 or Gal83). The SNF1 complex regulates function of glucose-responsive transcriptional activators.
In plant cells, there is increasing evidence for a diverse array of glucose, sucrose and trehalose induced signaling mechanisms. Plant sugar-response pathways may employ homologs of some of the components of yeast sugar-signaling cascades (membrane sugar sensors, hexokinase, SNF and SCF complexes, kinases and protein phosphatases). Characterization of the plant sugar signaling pathways is complicated by the fact that they form part of a complex regulatory web that also includes phytohormones and environmental-response pathways.
In mammals, the response to glucose is complex because it combines effects related to glucose metabolism and to glucose-dependent hormonal modifications. Well-characterized glucose signaling in pancreatic ß-cells regulates expression of the proinsulin gene. The recent studies indicate that the glucose-dependent increase in the ATP: AMP ratio causes membrane depolarization, activating voltage-gated Ca2+-channels and insulin secretion.

Key words: sugars signaling pathways, sugar sensors, sugar response mutants, yeast, Arabidopsis thaliana, pancreatic ß-cells.
 

Trail - Apoptosis Induction Mechanisms and its Employment in CancerTherapy

Summary: TRAIL (TNF-Related Apoptosis Inducing Ligand) is a newly discovered cytokine able to induce apoptosis in tumor cells with a limited cytotoxicity to most of normal cells. TRAIL can induce apoptosis as a soluble, trimeric ligand or it can be absorbed on effector cells membrane. TRAIL mediates cell death binding to its receptors on cell surface (TRAIL-R1 and TRAIL-R2). The other TRAIL receptors, TRAIL-R3, TRAIL-R4 and OPG are decoy receptors, unable to induce apoptosis. Approximately 60% of examined tumor cells are sensitive to TRAIL mediated cell death. Thus TRAIL is a potential and promising candidate for cancer therapy.

Keywords: TRAIL, TNF, apoptosis, cancer therapy, caspase.
 

Caspases of the Verbates - Their Role in Apoptosis

Summary: Apoptosis or programmed cell death is a physiological process responsible for normal development and maintenance of homeostasis in multicellular organisms. This process involves well working suicide machinery which core component is a family of cysteinyl-dependent aspartate proteases known as caspases. These enzymes lie in a latent form in cells and become activated in response to a wide variety of cell death stimuli. This review summaries main progress made on structure, mechanism of enzyme activation, catalytic properties, substrates of caspases and regulation of their activity. The article presents also an involvement of caspases in major apoptosis pathways.

Key words: apoptosis, caspases, regulation of caspase activity, substrates.
 

Characterisation of Platelets ADP Receptors

Summary: Platelet ADP receptors play a crucial role in thrombosis and also in artheriosclerosis. The P2Y receptors are coupled to G proteins, and it results in activation of secondary intraplatelet signalling. The P2Y1 receptor causes calcium ions release and this way initiates platelet aggregation, wheraes recently identified receptor P2Y12,  by inhibition of adenyl cyclase, is necessary for full response. On the other hand, the P2X1 receptor is a fast ionic channel, but its role in platelet activation still remains unclear. Platelet ADP receptors are potential targets for antiplatelet drugs. At present two antiplatelet agents acting on ADP receptors are available, i.e. ticlopidine and cropidogrel. Knowledge of the role of ADP receptors in platelet activation and aggregation processes makes possible prevention in artheriosclerosis.

Key words: ADP, platelets, purinoreceptors P2, antiplatelet drugs.
 

Centromeric DNA  and  Proteins

Summary: The common feature of the centromeric DNA studied till now is the presence of long tandem arrays in which the monomeres may slightly differ in their nucleotide sequences. Some general similarities have been found among Primates, as well as among related higher plant species. In grasses the retroelements from gypsy  and copia families, whose little amount may be present in dicotyledonous species, constitute the main components of centromeric DNA. The variety  of DNA centromeric sequences and the presence in active neocentromeres of DNA sequences different from those in normal centromeres in the same species bring some doubts about the essential significance of DNA in centromere function, i.e. kinetochore formation. The results of comparative studies on the presence of centromeric proteins (CENPs) in normal centromeres, neocentromeres, active and non-active centromeres in dicentric chromosomes indicate that among constitutive proteins CENP-A and CENP-C and among facultative ones CENP-E and CENP-F are indispensable for centromere function.

Key words: centromeric DNA, centromeric proteins, higher plants, mammals.

C Cells of the Thyroid Gland and their Function

Summary: Parafollicular cells ( C ), belonging to dispersed neuroectodermal endocrine cells system (APUD), play important and not clearly explained part in homeostasis of all the organism. Every year brings newer and newer discoveries showing their structure and function complexity. C cells have receptors for various hormones and are the source of numerous regulating peptides of auto-, para- and endocrine activity. Some of them, among other calcitonin and somatostatin, have a practical meaning and are used in the treatment of many diseases. Multiorgan receptors localization for mentioned peptides suggests the possibility of systemic multidirectional reaction. They are of principal significance in intracellular metabolism regulation, cells growth and differentiation, calcium and phosphorus metabolism, and influence other hormones synthesis and release. The puzzle and multiple functions of C cells was the ground on which we have tried to present the current state of knowledge.

Key words: C cells, regulatory peptides, calcitonin, calcitonin receptor.
 

Katarzyna SKÓRZYŃSKA, Joanna KOLANO, Janusz KOCKI, Jacek WOJCIEROWSKI

The TRF1/TRF2 and the TANK1/TANK2 Proteins and their Role in the Telomers Length Regulation

Summary: Telomeres are the end fragments of the chromosomes, protecting them from inappropriate DNA repair mechanisms. The length of telomeres is regulated by interactions of a number of different proteins: TRF1, TRF2, TIN2, TANK1, TANK2. TRF1 and TRF2 proteins are involved in forming specific structures called t-loops, which protect telomeres from end-to-end fusions. TANK1 and TANK2, belonging to a class of proteins called PARPs, regulate telomere function by poly(ADP-ribosyl)ation.  Because of systematic loss of telomeric repeats during cell divisions, telomerase  and associated proteins are necessary to maintain genomic stability. Interactions between all this factors are very complexed and still poorly known.
Key words:  telomeres, telomerase, TRF1, TRF2, TIN2, PARPs, TANK1, TANK2.