25-01-2013, 02:01 PM
BioArena Studies: Unique Function of Endogenous Formaldehyde and Ozone in the Antibiotic Effect – A Review
[attachment=48455]
INTRODUCTION
It is known that the so-called “antibiotic era” is already
five decades old, nevertheless the mankind faced with a
global problem of emerging resistance of virtually all pathogens
[1]. The majority of the human diseases is originating
from the different infections, therefore, infectious agents can
cause different human diseases [2, 3]. The recognition and
knowledge of these factors is a big challenge of the modern
chemical-biochemical analysis. However, microbes and medicinal
plants contain thousands of constituents and so are
valuable sources of new and biologically active substances,
e.g. antibiotics, antineoplastics, and herbicides [4]. To study
these it is important to have suitable analytical chemical
methods and biological assays.
Focusing on the detection of antibiotic-like substances direct
bioautography, combining the application of planar layer
liquid chromatographic separation and post-chromatographic
bioassay, can be regarded as the most efficacious assay [5].
Although, direct bioautography is a leading bioassay technique
among the bioautographic techniques, nowadays it is
already not enough. Conventional bioautographic technical
solutions are unsuitable for studying and understanding all
the complicated biochemical reactions involved. Model experiments
are necessary with modern separation and detection
systems at micro level. The so-called BioArena system,
the first basically further development of direct bioautography,
can be used to exploit the potential of bioautography [6,
7]. The development of BioArena system (i.e. coordination
of operating steps, use of specific series of exogenous and/or
endogenous molecules [8-10]) leads to new possibilities in
bioassay-guided detection, fractionation and isolation.
BioArena integrates the advantages of layer liquid chromatography
(ideally, variants of linear OPLC [11, 12]) with
basic direct bioautography [13] and visual, spectroscopic and
*Address correspondence to this author at the Plant Protection Institute,
Hungarian Academy of Sciences, Herman O. Str. 15, 1022 Budapest, Hungary;
spectrometric evaluation of chromatographic spots before
and after biological detection. This integration utilizes the
possibilities of interactions of microbes with small and large
co-factor molecules in the adsorbent layer after chromatographic
separation. These endogenous and/or exogenous
molecules are available for the cells of the indicator organism
in the culture medium on the adsorbent layer (more exactly
in the chromatographic spots or bands [14-16]). The
possibility of addition of such small and large co-factor
molecules to the culture medium (so to chromatographic
spots) is unlimited.
On the basis of up-to-date theoretical and practical biological
and biochemical results obtained by use of the
BioArena system the formaldehyde (HCHO) and ozone (O3)
as characteristic key small molecules play a crucial role in
the antibiotic effect of most diverse chemical substances
[17]. Therefore, it is especially interesting to know and to
understand better the function and place of these molecules
in biological world. This is particularly actual aim because it
seems that these molecules are determining factors in the
antibiosis and the resistance, alike.
In future investigation with BioArena system it has to
take into account that the in vitro results (BioArena investigations)
can be extended to in vivo conditions [17]. This
means the new, useful utilization of results from planar layer
liquid chromatographic separations.
BIOCHEMICAL-CHEMICAL BACKGROUND OF
THE EXPERIMENTS
Occurrence and Function of Formaldehyde in Biological
Systems
According to recent observations formaldehyde (HCHO)
is an endogenous component of all biological systems [18,
19], mainly in the form of hydroxymethyl group. Therefore,
it can be detected and measured in different biological samples
using a HCHO capture molecule (e.g. dimedone) for
collecting HCHO molecules from a given biological unit [8].
It has to note that this simplest aliphatic aldehyde is mainly
/12 $58.00+.00 2012 Bentham Science Publishers
76 Medicinal Chemistry, 2012, Vol. 8, No. 1 Tyihák et al.
formed during enzymatic methylation and demethylation
processes [20, 21], but there are also other origins [22-24]. It
is becoming increasingly evident that there is a primary
HCHO cycle in biological systems in which the formation of
the S-methyl group of L-methionine from HCHO originating
from natural HCHO generators and that the HCHO-yielding
function of S-adenosyl-L-methionine (SAM) are essential
components of this fundamental biochemical pathway (Fig.
1) [18, 19]. HCHO can be continuously formed by almost all
cells both intracellularly and extracellularly. The term “formaldehydome”
means the complete set of HCHO-cyclemediated
and non-mediated HCHO pathways of a given biological
unit (Fig. 2) [17]. In fact the nature of the distribution
of HCHO molecules as methyl and/or hydroxymethyl/formyl
groups, and the demethylation of the different methylated
and/or hydroxymethylated compounds fundamentally affect
the composition of the formaldehydome and result in the
characteristic profile of a biological unit [7]. The formaldehydome
can interlace the big biological units such as genome,
proteome etc. by means of dynamic methylation, hydroxymethylation,
formylation and other such processes.
HCHO is a determining endogenous component of all biological
systems.
These studies with bound and free HCHO opened really
new horizons in biology and so the more recent observations
suggest that different cancer tissues directly secret endogenous
HCHO and this, at low concentration, induces metastatic
bone cancer pain through TRPV1 activation. This process
is particularly active in acidic tumor environments [25].
It is especially interesting that HCHO scavengers decrease
pain responses by decreasing HCHO level. Furthermore,
HCHO level was significantly increased in the autopsy hippocampus
from Alzheimer’s patients. Cognitive impairments
of senile dementia are also probable related to endogenous
HCHO levels [26]. Recent studies illustrated a functional
link between the histone deacetylase complexes and specific
histone demethylase [27].
[attachment=48455]
INTRODUCTION
It is known that the so-called “antibiotic era” is already
five decades old, nevertheless the mankind faced with a
global problem of emerging resistance of virtually all pathogens
[1]. The majority of the human diseases is originating
from the different infections, therefore, infectious agents can
cause different human diseases [2, 3]. The recognition and
knowledge of these factors is a big challenge of the modern
chemical-biochemical analysis. However, microbes and medicinal
plants contain thousands of constituents and so are
valuable sources of new and biologically active substances,
e.g. antibiotics, antineoplastics, and herbicides [4]. To study
these it is important to have suitable analytical chemical
methods and biological assays.
Focusing on the detection of antibiotic-like substances direct
bioautography, combining the application of planar layer
liquid chromatographic separation and post-chromatographic
bioassay, can be regarded as the most efficacious assay [5].
Although, direct bioautography is a leading bioassay technique
among the bioautographic techniques, nowadays it is
already not enough. Conventional bioautographic technical
solutions are unsuitable for studying and understanding all
the complicated biochemical reactions involved. Model experiments
are necessary with modern separation and detection
systems at micro level. The so-called BioArena system,
the first basically further development of direct bioautography,
can be used to exploit the potential of bioautography [6,
7]. The development of BioArena system (i.e. coordination
of operating steps, use of specific series of exogenous and/or
endogenous molecules [8-10]) leads to new possibilities in
bioassay-guided detection, fractionation and isolation.
BioArena integrates the advantages of layer liquid chromatography
(ideally, variants of linear OPLC [11, 12]) with
basic direct bioautography [13] and visual, spectroscopic and
*Address correspondence to this author at the Plant Protection Institute,
Hungarian Academy of Sciences, Herman O. Str. 15, 1022 Budapest, Hungary;
spectrometric evaluation of chromatographic spots before
and after biological detection. This integration utilizes the
possibilities of interactions of microbes with small and large
co-factor molecules in the adsorbent layer after chromatographic
separation. These endogenous and/or exogenous
molecules are available for the cells of the indicator organism
in the culture medium on the adsorbent layer (more exactly
in the chromatographic spots or bands [14-16]). The
possibility of addition of such small and large co-factor
molecules to the culture medium (so to chromatographic
spots) is unlimited.
On the basis of up-to-date theoretical and practical biological
and biochemical results obtained by use of the
BioArena system the formaldehyde (HCHO) and ozone (O3)
as characteristic key small molecules play a crucial role in
the antibiotic effect of most diverse chemical substances
[17]. Therefore, it is especially interesting to know and to
understand better the function and place of these molecules
in biological world. This is particularly actual aim because it
seems that these molecules are determining factors in the
antibiosis and the resistance, alike.
In future investigation with BioArena system it has to
take into account that the in vitro results (BioArena investigations)
can be extended to in vivo conditions [17]. This
means the new, useful utilization of results from planar layer
liquid chromatographic separations.
BIOCHEMICAL-CHEMICAL BACKGROUND OF
THE EXPERIMENTS
Occurrence and Function of Formaldehyde in Biological
Systems
According to recent observations formaldehyde (HCHO)
is an endogenous component of all biological systems [18,
19], mainly in the form of hydroxymethyl group. Therefore,
it can be detected and measured in different biological samples
using a HCHO capture molecule (e.g. dimedone) for
collecting HCHO molecules from a given biological unit [8].
It has to note that this simplest aliphatic aldehyde is mainly
/12 $58.00+.00 2012 Bentham Science Publishers
76 Medicinal Chemistry, 2012, Vol. 8, No. 1 Tyihák et al.
formed during enzymatic methylation and demethylation
processes [20, 21], but there are also other origins [22-24]. It
is becoming increasingly evident that there is a primary
HCHO cycle in biological systems in which the formation of
the S-methyl group of L-methionine from HCHO originating
from natural HCHO generators and that the HCHO-yielding
function of S-adenosyl-L-methionine (SAM) are essential
components of this fundamental biochemical pathway (Fig.
1) [18, 19]. HCHO can be continuously formed by almost all
cells both intracellularly and extracellularly. The term “formaldehydome”
means the complete set of HCHO-cyclemediated
and non-mediated HCHO pathways of a given biological
unit (Fig. 2) [17]. In fact the nature of the distribution
of HCHO molecules as methyl and/or hydroxymethyl/formyl
groups, and the demethylation of the different methylated
and/or hydroxymethylated compounds fundamentally affect
the composition of the formaldehydome and result in the
characteristic profile of a biological unit [7]. The formaldehydome
can interlace the big biological units such as genome,
proteome etc. by means of dynamic methylation, hydroxymethylation,
formylation and other such processes.
HCHO is a determining endogenous component of all biological
systems.
These studies with bound and free HCHO opened really
new horizons in biology and so the more recent observations
suggest that different cancer tissues directly secret endogenous
HCHO and this, at low concentration, induces metastatic
bone cancer pain through TRPV1 activation. This process
is particularly active in acidic tumor environments [25].
It is especially interesting that HCHO scavengers decrease
pain responses by decreasing HCHO level. Furthermore,
HCHO level was significantly increased in the autopsy hippocampus
from Alzheimer’s patients. Cognitive impairments
of senile dementia are also probable related to endogenous
HCHO levels [26]. Recent studies illustrated a functional
link between the histone deacetylase complexes and specific
histone demethylase [27].