| Volume 6 (2001) pp 3-52 |
| Title |
MOLECULAR MECHANISMS OF RETINOID ACTION |
| Authors |
Hinrich Gronemeyer1* and Roman Miturski2 |
| Abstract |
In the past few years our understanding of nuclear receptor (NR)
action has been dramatically improved. This is due to to advancements in three
fields, (i) 3D structure determination, (ii) analysis of the complexes formed
between nuclear receptors and co-regulatory molecules, and (iii) the genetic
analysis of nuclear receptor signalling by gene "knock out" and "knock in"
technologies. The elucidation of the crystal structure of apo-, holo (agonist)-
and antagonist-NR ligand-binding domain (LBD) complexes is of outstanding
importance for our understanding of the structural principles, in particular of the
ligand-induced allosteric alterations, that are at the basis of receptor action. The
concomitant identification and functional analysis of co-regulators (TIFs, coactivators
and co-repressors) previously predicted from squelching studies have
provided the possibility to understand the propagation of the original signal
from ligand binding through intramolecular allosteric effects to intermolecular
interactions. Recent crystal data of receptor LBD heterodimers and LBDagonist
complexes with nuclear receptor interacting peptides of co-activators
have provided molecular insights into receptor dimerization and receptorcoactivator
interaction. Finally, analysis of the signalling compexes established
over nuclear receptors, assembling enzymatic activities that can alter the
acetylation status of chromatin at the promoter regions of target genes and
(de)acetylate other transcription regulatory factors paves the way to a
comprehension of receptor action at the chromatin level. But much remains to
be learnt and the recent studies have pointed towards an enormous complexity
of this signalling system. Insights into the mechanistic basis of promyelocytic
leukemia and the role of retinoic acid in differentiation therapy have been obtained as a consequence of the above studies, justified the efforts and led to
an increasing awareness of the nuclear receptor signalling systems in basic and
applied research. Here we will review recent data with the focus on what we
have learnt about the interplay between NR structure and function to provide a
view of the early steps of nuclear receptor action. |
| Address and Contact Information |
1Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC),
CNRS/INSERM/ULP, BP 163, 67404 Illkirch Cedex, C. U. de Strasbourg,
France,
2Second Department of Gynaecological Surgery, Medical University,
Lublin, Poland |
 ![[Rozmiar: 1332 bajtĂłw]](pic/abstract.gif) |
| Volume 6 (2001) pp 53-57 |
| Title |
COMMENTS ON A STUDY BY WOLF, SIWY, KORCHEV AND
SPOHR PUBLISHED IN CELL. MOL. BIOL. LETT. 4 (1999) 553-565 |
| Authors |
Dietrich Woermann |
| Abstract |
Attention is drawn to the fact that the non-linear electrical currentvoltage
characteristic of porous track-etched poly(ethylene terephtalate)
membranes, reported by Wolf, Siwy, Korchev and Spohr in Cell. Mol. Biol.
Lett. 4 (1999) 553-565, is very similar to that observed with cross-linked
polyelectrolyte gel membranes with negatively charged fixed ionic groups
(cation exchange membranes). This similarity was overlooked by the authors.
The physics of the current-voltage behaviour of cation exchange membranes is
fairly well understood. Experiments are proposed with the aim of finding out
whether the physics causing the non-ohmic current voltage characteristic is the
same for both types of membranes. |
| Address and Contact Information |
Institute of Physical Chemistry, University of Köln,
Luxemburger Strasse 116, 50939 Köln, Germany |
|
| Volume 6 (2001) pp 59-69 |
| Title |
THE NUCLEAR MATRIX AND CHROMOSOMAL DNA LOOPS: IS
THEIR ANY CORRELATION BETWEEN PARTITIONING OF THE
GENOME INTO LOOPS AND FUNCTIONAL DOMAINS? |
| Authors |
Sergey V. Razin |
| Abstract |
In this paper we are presenting a critical analysis of the results of
experiments aimed to elucidate the principles of the eukaryotic genome
structural-functional organization. Although the DNA loops attached to the
nuclear matrix (chromosomal scaffold) are frequently considered as
independent functional domains, this supposition lack experimental proofs as
far as the transcriptional domains are concerned. On the contrary, many
observations indicate that organization of chromosomal DNA into loops is
directly related to the replicon structure of the genome. |
| Address and Contact Information |
Laboratory of Structural and Functional Organization of Chromosomes,
Institute of Gene Biology of the Russian Academy of Sciences, Vavilov Str.
34/5, 117334 Moscow, Russia |
|
| Volume 6 (2001) pp 71-81 |
| Title |
THE ANTIOXIDANT ACTIVITY OF BHT AND NEW PHENOLIC
COMPOUNDS PYA AND PPA MEASURED BY
CHEMILUMINESCENCE |
| Authors |
Anna Krasowska1, Dawid Rosiak1, Katarzyna Szkapiak1,
Małgorzata Oświecimska2, Stanisław Witek2
and Marcin Łukaszewicz1* |
| Abstract |
The antioxidative properties of two series of new phenolic,
amphiphilic compounds were evaluated using the chemiluminescence (CL)
method. 2,2'-Azobis (2-amidinopropane) dihydrochloride (AAPH) was used as
a source of free radicals, to obtain high and prolonged CL. Three different kinds
of buffers (organic and inorganic) were tested. The CL level varied only slightly
depending on the buffer but increased significantly with the pH. Twelve newly
synthesised compounds were compared with butylated hydroxytoluene (BHT),
a commercially used antioxidant. The new antioxidants included two classes of
quaternary ammonium salts with a phenol substituent functioning as an
antioxidant. The salts were synthesised by quaternarization of pyrrolidine ethyl
esters of dihydrocinnamic acid by n-alkoxymethyl bromides (PYA-n) or
quaternarization of 2-dimethylaminoethyl esters by n-alkyl bromides (PPA-n).
All the tested compounds quenched CL proportionally to their concentrations.
In our experimental conditions 8.5 mM BHT quenched 50% of the CL. The
PYA and PPA compounds had IC50 two to six times lower than BHT. CL
inhibition was proportional to the pH for all antioxidants. The relationships
between the structure and activity of the tested compounds are discussed. |
| Address and Contact Information |
1Institute of Microbiology, Wroclaw University, Przybyszewskiego 63-77,
51-148, Wroclaw, Poland,
2Institute of Organic and Polymer Technology,
Technical University of Wroclaw, Wybrzeze Wyspianskiego 27, Wroclaw,
Poland
*Corresponding author: lukasz@microb.uni.wroc.pl |
|
| Volume 6 (2001) pp 83-91 |
| Title |
NEW AMINOPHOSPHONATES WITH ANTIOXIDATIVE ACTIVITY |
| Authors |
Halina Kleszczynska and Janusz Sarapuk |
| Abstract |
The antioxidative activity of some newly synthesized
aminomethanephosphonic acid derivatives was studied. The compounds studied
differed in their polarity and the hydrophobicity of the electronic substituents at
their nitrogen and phosphorus atoms. It was found that all the
aminophosphonates studied, both cyclic and acyclic, protected erythrocyte
membranes against peroxidation to some extent. The effect was somewhat
weaker in the case of cyclic compounds, and for erythrocytes irradiated with
UV light.
The cyclic compounds provided no protection of erythrocytes illuminated by
natural light.
The observed differences between the antioxidative activities of cyclic and
acyclic compounds are probably related to differences in their ability to
incorporate into the lipid phase of erythrocyte membranes. Once incorporated,
they change the fluidity of the membranes. The extent of those changes was
determined in fluorescence measurements. Generally, they were found to be
more pronounced in the case of acyclic aminophosphonates, although as regards
other structural differences between particular aminophosphonates, a clear
picture of the relationship between structure and effect is more difficult to
obtain. No correlation was found between the antioxidative efficiency of the
compounds and the fluidity changes they induce. |
| Address and Contact Information |
Department of Physics and Biophysics, Agricultural University, Wroclaw,
Norwida 25, 50-375, Poland |
|
| Volume 6 (2001) pp 93-105 |
| Title |
THE "PATCH-CLAMP" TECHNIQUE AND ITS APPLICATION IN
INVESTIGATIONS OF THE PROPERTIES OF HUMAN T
LYMPHOCYTE POTASSIUM CHANNELS |
| Authors |
Andrzej Teisseyre |
| Abstract |
The first part of this review presents a historical outline on the
development of experimental methods in electrophysiology starting from the
first experiments performed in the 1920s and ending with the „patch-clamp”
technique. Recording configurations of the „patch-clamp” technique are briefly
reviewed in the second section. The areas of application of the configurations
are shown.
The last section contains a short review on the available data of “patch-clamp”
studies on the expression and properties of potassium channels in human T
lymphocytes (TL). Problems that require further investigation are briefly
presented. |
| Address and Contact Information |
Department of Biophysics, Wroclaw Medical University
Chałubińskiego 10, 50-368 Wroclaw, Poland. |
|
