Izabela MŁYNARCZUK-BIAŁY

Enigmatic Tripeptidylpeptidase II – Protease for Special Tasks

Summary: Tripeptidylpeptidase II is a giant cytoplasmatic protease that removes tripeptides from free amino acid end of oligopeptides and it has also some endoproteolytic activity. TPPII is present in all examined eukaryotic cells. Its structure is highly conserved. Together with the proteasome and other cytoplasmic proteases, TPPII participates in degradation of proteins, however its specific substrates and regulation of its activities still remain to be elucidated. Both over-expression of TPPII as well as its knock down are harmful for the cell. In the first case, regulation of the cell cycle is disturbed that may favor malignant transformation, in the second case the cells divide slower and have defects in kariokinesis. TPPII serves special functions in different tissues participating in lipogenesis, kacheksy, neuronal transmission, antigen presentation and onkogenesis.

Key words:  tripeptidylpeptidase II, TPPII, proteasome, kacheksy, apoptosis, lipogenesis, onkogenesis

[Postępy Biologii Komórki 2008; 35: 427–439]

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Maciej MAŁECKI*, Agnieszka GŁADYSZ, Katarzyna MOŚCICKA, Agnieszka LIPIEC

Sonic Hedgehog – a Morphogen with Therapeutic Importance

Summary: A development of contemporary methods of therapy as gene therapy is directly based on a search of genes that encode therapeutic proteins. Angiogenic gene therapy takes advantage of genes encoding proangiogenic factors. It is described that embryonic sonic hedgehog protein is a strong stimulator of neovascularization. Sonic hedgehog is implicated in the regulation of central nervous system polarity and differentiation of various organs. Recent findings indicate that sonic hedgehog based gene therapy accelerates wound healing by enhancing endothelial progenitor cell-mediated microvascular remodeling. It is also known that SHH induces arteriogenesis. Further studies of complex SHH signaling pathway will reveal whether  proangiogenic potency of sonic hedgehog protein determine the progress of cardiovascular gene therapy.

Key words:
 sonic hedgehog  (SHH), signal transduction, angiogenic gene therapy
[Postępy Biologii Komórki 2008; 35: 441–452]

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Katarzyna KULCENTY, Marcin HOŁYSZ, Wiesław H. TRZECIAK

Steroidogenic Factor-1: Structure, Action Mechanism and Biological Role

Summary: Structure, mechanism of  action and biological role of steroidogenic factor-1 (SF-1), in particular the significance of this factor for the normal function of the adrenal cortex, have been presented. SF-1 is a transcription factor, classified to an orphan nuclear receptor family, which interacts with the specific nucleotide sequence within promoters of the target genes, including those encoding proteins participating in the synthesis or  transport of  steroid hormones or their precursors in the cell. Structure of the SF-1 gene, transcript and protein was presented as well as the regulation of  SF-1 expression and transcriptional activity of the protein product of the gene. Major genes regulated by SF-1 were mentioned and many of them characterized. The role of SF-1 in the origin of adrenocortical carcinomas and prospects of SF-1 application in the treatment of the diseases of the adrenal cortex were discussed. 

Key words:  steroidogenic factor-1 (SF-1), structure, target genes,  regulation, function, role, potential applications
[Postępy Biologii Komórki 2008; 35: 453–466]

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Małgorzata STAŃCZYK, Ireneusz MAJSTEREK

Apoptosis – Targeted Anticancer Therapy 

Summary: Apoptosis is the major form of cell suicide. Most conventional anticancer agents induce apoptosis indirectly. Although chemiotherapeutic drugs should selectively kill only tumor cells, normal cells are often susceptible to cytotoxic or cytostatic effects of these agents. This is a reason of potentially harmful side effects including inflammation and damage to the surrounding normal tissue. A new therapeutic approach in cancer treatment is the use of substances that stimulate cytokine production, angiogenesis inhibitors, gene therapies, antisense oligonucleotides and monoclonal antibodies. Many of new agents tested in preclinical study or in I and II phase of clinical trials can induce apoptosis directly. This new approach allows probably to eliminate a lot of problems connecting with non-specific activity of anticancer drugs and their mutagenicity.

Key words: 
apoptosis, mitochondria, TNF, caspases, NF-kB, Akt/PKB, glutathione, antisense oligonucleotides, death genes
[Postępy Biologii Komórki 2008; 35: 467–484]

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Katarzyna STARSKA, Marek ŁUKOMSKI

Regulation of Differentiation and Proliferation in Immunocompetent Cells, Cytokines and Growth Factors Secretion in Neoplasm Disease and Role Suppression of Carcinogenesis and Tumor Growthon Mechanism of SOCS/CIS Family Activation

Summary: Regulatory proteins SOCS 1-7 (suppressors of cytokine signaling), CIS (cytokine-inducible SH2 protein) and other intracellular molecules such as JAKs (Janus tyrosine kinases), STATs family (signal transducers and activators of transcription), which participate in immunological response, could influence differentiation and proliferation, cell apoptosis, cell-cycle progression, cytokines and growth factors secretion by regulation of proper genes which determine these process in neoplasm cells and blood cells. The aim of this study was to introduce the latest knowledge of the SOCS/CIS family function in regulation of these processes. In this study the characterization of SOCS/CIS proteins and role in immunocompetent cells activation, their differentiation, proliferation, cytokines secretion and regulatory mechanisms of carcinogenesis and neoplasm progression as well as interactions between SOCS1-7, CIS and proteins which determine regulation of lymphocytes T activity (ZAP70, Gfi-1, p27kip1) and oncogenesis (JAKs, STATs, p65, FAK, c-kit i IRS1/2) were introduced. Knowledge of mechanisms  of activation by SOCS/CIS family, both in neoplasm cells and immunocompetent cells, could allow to understand intracellular interactions between these molecules, learn dominate processes in cancer disease and use new therapeutic methods (immunotherapy, new criterions for operations).

Key words:  immunocompetent cells, neoplasm cells, carcinogenesis, tumor growth, SOCS/CIS proteins

[Postępy Biologii Komórki 2008; 35: 467–484]

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Anna KONDAREWICZ, Fabian URBAN, Mariola MARCHLEWICZ, Barbara WISZNIEWSKA 

Estrogens  in  Male  Reproductive  System 

Summary: The presence of estrogens in the male gonad is now well documented, however the role of the hormones in regulation of function of male reproductive system is not fully understood. The using of molecular biology methods provided evidence that the cells of male reproductive system organs are able to produce estrogens via aromatization of androgens and are estrogen target. The cytochrome P450 aromatase and both isoform of estrogen receptors are expressed not only in Leydig and Sertoli cells, but also in germ cells, spermatozoa, the cells of epithelium in the efferent ductules and epididymis. In view of the widespread distribution of aromatase and estrogen receptors in the cells of male reproductive system, the role of estrogens in male reproduction is more complex than previously realized.

Key words:   aromatase, estrogens, estrogen receptors, male reproductive system

[Postępy Biologii Komórki 2008; 35: 499–516]

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Joanna OLKOWSKA-TRUCHANOWICZ

Isolation and Characterization of Adipose Tissue-Derived Stem Cells

Summary:  Main sources, isolation methods and culturing of multipotent adipose tissue-derived stem cells were described in the paper, considering distinct properties depending on isolation technique, source and time in the culture. Based on literature their molecular properties and surface markers presence were summarized.

Key words:  adult stem cells, mesenchymal stem cells, multipotent stem cells, adipose tissue, stromal vascular fraction 

[Postępy Biologii Komórki 2008; 35: 517–526]

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