Volume 50 (2004) No. 5

Volume 50 (2004) No. 5
Review
The Biological Functions of β3 Integrins
K. SWITALA-JELEN1, K. DABROWSKA1, A. OPOLSKI1, L. LIPINSKA1, M. NOWACZYK2,
A. GORSKI1,2 ..............................................................................................................143
1
Institute of Immunology and Experimental Therapy, Wroclaw, Poland
2Institute of Transplantology, Medical University of Warsaw, Warsaw, Poland
Corresponding author: Kinga Switala-Jelen, Institute of Immunology and Experimental Therapy, Polish Academy of Sciences,
R. Weigla 12 St., 53-114 Wroclaw, Poland. Tel.: (+48) 713 371 172; Fax: (+48) 713 371 382; e-mail: switala@iitd.pan.wroc.pl
Abstract.
Full text. 143-152
Original Articles
The Frequency of Alleles of the Pro12Ala Polymorphism in PPARγ2 Is Different between Healthy Controls and
Patients with Type 2 Diabetes
D. PINTÉROVÁ1, M. ČERNÁ1, K. KOLOŠTOVÁ1, P. NOVOTA1, M. ČIMBUROVÁ1, M. ROMŽOVÁ1,
A. KUBĚNA1,3, M. ANDĚL2......................................................................................153
1Division of Cell and Molecular Biology, 3rd Faculty of Medicine, Charles University, Prague, Czech Republic
22nd Department of Internal Medicine, 3rd Faculty of Medicine, Charles University, Prague, Czech Republic
31st Faculty of Medicine, Charles University, Prague, Czech Republic
Corresponding author: Daniela Pintérová, Division of Cell and Molecular Biology, Third Faculty of Medicine,
Charles University, Ruská 87, CZ-100 00 Prague 10, Czech Republic. Tel: (+420) 267 102 666, Fax: (+420) 267 102 650, e-mail: pinterod@seznam.cz
Abstract.
Full text. 153-156

A Gly482Ser Polymorphism of the Peroxisome Proliferator-Activated Receptor-γ Coactivator-1 (PPARGC1)
Gene Is Associated with Type 2 Diabetes in Caucasians

T. KUNEJ1, M. GLOBOČNIK PETROVIČ2, P. DOVČ1, B. PETERLIN3, D. PETROVIČ4.................................157
Department of Animal Science, Biotechnical Faculty, University of Ljubljana, Domzale, Slovenia
Eye Clinic, University Medical Centre Ljubljana
Division of Medical Genetics, Department of Obstetrics and Gynecology, Medical Centre Ljubljana, Slovenia
Institute of Histology and Embryology, Medical Faculty, University of Ljubljana
Corresponding author: Daniel Petrovič, Institute of Histology and Embryology, Medical Faculty of Ljubljana,
Korytkova 2, 1105 Ljubljana, Slovenia. Tel.: (+386) 61 543 7367; Fax (+386) 61 1401 294; e-mail: daniel.petrovic@mf.uni-lj.si
Abstract.
Full text. 157-158

Repression of the Melanocyte-Specific Promoter of the Microphthalmia-Associated Transcription Factor by
the Adenoviral E1A 12S Oncoprotein

 B. DRDOVÁ, J. VACHTENHEIM..........................................................................................159
Laboratory of Molecular Biology, University Hospital, 3rd Medical Faculty, Charles University  Prague,  Czech Republic
Corresponding author: Jiří Vachtenheim, Laboratory of Molecular Biology, University Hospital, Clinic of Pneumology,
3rd Medical Faculty, Charles University Prague, Budinova 2, 18000 Prague 8,  Czech Republic. Tel.: (+420) 266082272; Fax: (+420) 284840840; e-mail: jivach@upn.anet.cz.
Abstract.
Full text. 159-166 

Non-adherent  Bone  Marrow  Cells  Are  a  Rich  Source  of  Cells  Forming  Bone  in  Vivo
K. H. WŁODARSKI, R. GALUS, P. WŁODARSKI.............................................................167
Chair and Department of Histology and Embryology, Center of Biostructure, Medical Academy at Warsaw, Poland
Corresponding author: Krzysztof H. Włodarski, Chair and Department of Histology, Center of Biostructure, Medical Academy, 02-004 Warszawa, Chałubińskiego 5, Poland. Tel.: (+48) 226281041 (ext. 21 or 47); Fax: (+48) 226295282; e-mail: kwlodar@ib.amwaw.edu.pl
Abstract.
Full text. 167-173

Review
The Biological Functions of β3 Integrins
K. SWITALA-JELEN, K. DABROWSKA, A. OPOLSKI, L. LIPINSKA, M. NOWACZYK,
A. GORSKI

Integrins comprise a large family of αβ heterodimeric cell-surface receptors that are found in many animal species. They are expressed on
 a wide variety of cells. There are two members in the β3 integrin family: αIIbβ3 and αvβ3. This class of adhesion receptors mediates
cell-cell and cell-extracellular matrix interactions. Dysregulation of the β3 integrins is involved in the pathogenesis of many diseases
(including cancer) and in transplant rejection. Integrins also play a key role in many virus infectious cycles. In this paper the biological
functions of the β3 family are reviewed, with particular interest in its role in cancer progression and metastasis.
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Original Articles
The Frequency of Alleles of the Pro12Ala Polymorphism in PPARγ2 Is Different between Healthy Controls and
Patients with Type 2 Diabetes
D. PINTÉROVÁ, M. ČERNÁ, K. KOLOŠTOVÁ, P. NOVOTA, M. ČIMBUROVÁ, M. ROMŽOVÁ,
A. KUBĚNA, M. ANDĚL

The aim of this initial case-control study was to determine the association between common Pro12Ala polymorphism in the PPARγ2
gene and type 2 diabetes in the Czech Republic. Furthermore, the effect of this polymorphism on phenotypic characteristics and on levels
of lipids (total cholesterol, HDL-cholesterol, LDL-cholesterol and triglycerides) was studied. One hundred thirty-three patients with
type 2 diabetes and 97 control subjects were investigated. PCR and restriction fragment length polymorphism (RFLP) analysis were
used for identification of individual genotypes. In the group of patients, three samples (2.26%) were identified as homozygous for the Ala/Ala
genotype and 99 samples (74.44%) were homozygotes for the Pro/Pro genotype. Thirty-one samples (23.31%) were identified as
Pro12Ala heterozygous. In the control group, six samples (6.19%) were homozygous for the Ala/Ala genotype and 61 samples (62.89%)
were homozygotes for the Pro/Pro genotype. Thirty samples (30.93%) were identified as Pro12Ala heterozygous. The allele frequency
for the Ala allele was lower in the type 2 diabetic group than in the control group (13.91% vs. 21.43%, P = 0.022). There was no
difference (at P < 0.05) between the phenotypic characteristics (BMI, sex) studied in the group of patients according to the Pro12Ala
genotype. There was no significant effect of  the Pro12Ala polymorphism on lipid levels.
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A Gly482Ser Polymorphism of the Peroxisome Proliferator-Activated Receptor-γ Coactivator-1 (PPARGC1)
Gene Is Associated with Type 2 Diabetes in Caucasians

T. KUNEJ, M. GLOBOČNIK PETROVIČ, P. DOVČ, B. PETERLIN, D. PETROVIČ

The PPARGC1gene has been implicated in the regulation of several genes controlling energy metabolism. The prevalent
Gly482Ser polymorphism of the PPARGC1 gene has been shown to be associated with type 2 diabetes in some but not all studies.
The aim of this study was to analyse whether the Gly482Ser variant is a risk factor for development of type 2 diabetes in Slovene
population (Caucasians). Genotyping of the Gly482Ser polymorphism was performed for 545 subjects: 305 patients with type 2
diabetes and 240 non-diabetic controls. The Gly482Ser genotype distribution in patients with type 2 diabetes (AA = 11.5 %, AG = 42.3 %,
GG = 46.2 %) differed from genotype distribution in non-diabetic controls (AA = 6.3 %, AG = 46.3 %, GG = 47.5 %), and
the AA genotype was associated with 1.9-times increased risk of type 2 diabetes (95 % confidence interval 1.0–3.6; P = 0.036).
In conclusion, we suggest that the AA genotype of the Gly482Ser polymorphism of the PPARGC1 gene should be considered as
a risk factor for the development of type 2 diabetes in Caucasians.
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Repression of the Melanocyte-Specific Promoter of the Microphthalmia-Associated Transcription Factor by
the Adenoviral E1A 12S Oncoprotein

 B. DRDOVÁ, J. VACHTENHEIM

Melanocytes express MITF, which is crucial for the development of the melanocyte lineage and is overexpressed in malignant melanomas. Adenoviral E1A protein-expressing melanocytes are unpigmented, with the expression of MITF being silenced. We tested here a direct repression of the melanocyte-specific MITF promoter by E1A and its mutants. We found that the extreme N-terminus and conserved
region 1 are required for repression. In contrast, the motif in conserved region 2 (a.a. 122–126), as well as amino acids 26–35 at the N-terminus, are not necessary. As these two later motifs mediate E1A binding to the retinoblastoma protein or to the transcriptional
coactivator TRRAP, respectively, and are important for transformation by E1A in cooperation with other oncogenes, the results suggest
that the transformation-defective E1A can still efficiently repress the MITF promoter. The CREB binding motif-mutated promoter had lower activity, but was also repressed by the same E1A mutants in human melanoma cells. The E1A protein is known to also exert an antitumour activity, which is associated with its transcription repression function and the ability to induce apoptosis, and is a potential antimelanoma agent. Since recent data suggest that MITF may be a survival factor for melanoma cells, the E1A mutants described here might constitute a good targeting agent for antimelanoma therapy.
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Non-adherent  Bone  Marrow  Cells  Are  a  Rich  Source  of  Cells  Forming  Bone  in  Vivo
K. H. WŁODARSKI, R. GALUS, P. WŁODARSKI

Syngeneic, allogeneic and xenogeneic (rat) freshly isolated bone marow cells + stromal cell cultures maintained in vitro for 10–30 days,
as well as non-adherent cells removed from these cultures on 3rd–4th day were injected into the kidney parenchyma of mice,
 immunosuppressed with hydrocortisone. In syngeneic grafts the immunosuppression was omitted. In all transplant systems bone tissue was formed inside the kidney with 20% to 32% variation. Bone produced by allogeneic and xenogeneic cells is subject to rejection when immunosuppression ceases, as the bone formed is of donor origin. The „floating” cells, regardless of the transplant system, normally discarded during media replacement, turned out to be efficient bone producers. This notion is of practical implication when bone marrow cells are
used for bone healing.
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