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Current Enzyme Inhibition
ISSN: 1573-4080
Current Enzyme Inhibition
Volume 4, Number 2, July 2008
Contents
Impact of Omega-3 and Trans Fatty
Acids on Vascular Remodeling: Opposing Roles in Cardiovascular
Health Pp. 60-72
Rafat A. Siddiqui, Kevin Harvey, Steven
J. Miller and Gary Zaloga
[Abstract]
Mechanisms of Interaction of Nitric Oxide (NO)
and its Metabolites with Enzymes Responsible for the Physiological
Effects of NO Pp. 73-81
Vladimir Yu. Titov
[Abstract]
Neutrophil Elastase Inhibition: A New Cancer Therapy
Pp. 82-85
Takashi Sato, Miwa Yoshida, Satoshi Takahashi, Takashi
Fukutomi and Jun-Ichi Yamashita
[Abstract]
Study of the Catalytic Mechanism of the Enzyme Catalase
on Organic Hydroperoxides in Non-Polar Organic Solvent
Pp. 86-92
L. Campanella, G. Spuri Capesciotti, M.V.
Russo and M. Tomassetti
[Abstract]
Abstracts
[Back to top]
Impact of Omega-3 and Trans Fatty
Acids on Vascular Remodeling: Opposing Roles in Cardiovascular
Health
Rafat A. Siddiqui, Kevin Harvey, Steven
J. Miller and Gary Zaloga
Omega-3 polyunsaturated fatty acids (n-3 PUFAs) have
well-recognized cardio-beneficial effects that include reductions
in atherosclerotic lesions and mortality from myocardial infarction,
stroke, and sudden cardiac death. In contrast, evidence suggests
that more than 30,000 premature coronary deaths per year in
the US alone are associated with consumption of high levels
of trans isomers of unsaturated fatty acids, or trans
fatty acids (TFAs). Epidemiological evidence from four large
cohort studies overwhelmingly supports the conclusion that
TFAs are linked to coronary heart disease (CHD). CHD in patients
is associated with pathological vascular remodeling (PVR)
and impaired compensatory vascular remodeling (CVR). PVR is
characterized by thickening of vessel walls, reduction in
elasticity, and occlusion of vessels, resulting in restricted
blood flow. CVR represents a physiological process whereby
vessels from a pre-existing arteriolar network develop into
collateral arteries, effectively bypassing the site of arterial
occlusion. The structure and function of vascular endothelial
cell membranes are altered by both PVR and CVR. Oxidative
stress and the induction of endothelial adhesion molecules
promote PVR and inhibit CVR. It is known that n-3 PUFAs inhibit
the release of soluble adhesion molecules and proinflammatory
cytokines whereas TFA consumption has been linked to an increased
release of these proinflammatory mediators. However, it is
not known whether the changes in cell membrane composition
induced by n-3 PUFAs or TFAs impact development of PVR and
CVR directly or whether the changes result indirectly from
altered expression and/or release of proinflammatory mediators.
This review summarizes studies suggesting that n-3 PUFAs and
TFAs have opposing effects on endothelial cells and that their
effects on the endothelium might play an important role in
vascular remodeling.
[Back to top]
Mechanisms of Interaction of Nitric Oxide (NO)
and its Metabolites with Enzymes Responsible for the Physiological
Effects of NO
Vladimir Yu. Titov
It is known that nitric oxide (NO) realizes its basic physiological
effects by affecting activity of specific enzymes, such as
guanylate cyclase and caspase. Since NO itself in physiological
conditions is a short-lived substance, it is considered that
it acts by means of some metabolites such as nitrosothiols
and some nitro-compounds, which may serve as NO - donors.
These NO metabolites are relatively stable substances and
their concentrations in biological tissues are also relatively
stable. But in this case it is unclear how their physiological
effects are controlled. Could they, for example, respond to
the certain factors, be accumulated in the right place at
the right time or just dissociate releasing NO? In scientific
literature these questions remain unanswered.
In this review we present the result of our analysis of the
available scientific data from the different researchers on
the interaction of some NO-donors with guanylate cyclase,
caspase and catalase. We propose that NO-like effects of these
NO-donors are not the result of only their simple dissociation
with releasing of NO. Mostly it is a complex process that
starts with initial transformation of these substances into
nitrosyl-iron complexes. NO-group of this complex becomes
available for the interaction as nitrosation agent only at
the moment of destabilization of the complex, which can be
initiated by variation of iron associated ligands included
in the complex. The ligand content in the medium can be changed
depending on physiological conditions.
[Back to top]
Neutrophil Elastase Inhibition: A New Cancer Therapy
Takashi Sato, Miwa Yoshida, Satoshi Takahashi, Takashi
Fukutomi and Jun-Ichi Yamashita
Cancer cells enter the circulation and attach to endothelial
cells to pass through them and migrate over a distance to
enter the tissue of the metastatic organ to proliferate there.
In the same way, neutrophils drift in blood and adhere loosely
to adhesive molecules on the endothelial cells in an inflamed
area. They roll along the endothelial cells and then adhere
closely to the endothelial cells to penetrate vessel wall.
Neutrophils can destroy the basement membrane and migrate
over a distance to fight against foreign bodies. Thus, the
process that both of them follow is quite the same. Neutrophil
elastase (NE) is a neutral serine protease which has broad
substrate specificity under the physiological conditions,
and its excessive production results in digestion of not only
elastin, but also other extracellular matrix proteins. This
minireview summarizes our recent experimental and clinical
studies on NE/NE inhibition and cancer/cancer treatment based
on our original view point.
[Back to top]
Study of the Catalytic Mechanism of the Enzyme Catalase
on Organic Hydroperoxides in Non-Polar Organic Solvent
L. Campanella, G. Spuri Capesciotti, M.V.
Russo and M. Tomassetti
Catalases are enzymes composed of a protein and a prosthetic
group made up of iron porphyrin. The aim of the present research,
was to study the catalytic mechanism of catalase on organic
hydroperoxides rather than on hydrogen peroxide, when operating
in organic solvents such as decane or hexane. The investigation
was performed using gas chromatography and amperometry to
analyse the reagents and reaction products of the catalytic
reaction of catalase on tert-butylhydroperoxide or on cumene
hydroperoxide, carried out in decane. The analytical results
pointed to the hypothesis that, in this case, the organic
solvent is involved in the reaction. In the absence of other
reducing agents, therefore, a small percentage of it is oxidized
and this redox reaction presumably involves the molecular
oxygen present in solution, the consumption of which is determined
experimentally through amperometry. This interpretation was
confirmed in the gas chromatograms performed by the appearance
of new peaks formed as a result of the enzymatic reaction
in decane which are presumably to be attributed to species
derived from the oxidation of decane, such as decanol.
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