Biomedical subjects

Krystian Kaletha

Publications and source records attributed to Krystian Kaletha.

8 recordsLinked to original sources

PubMed2005

Carbon monoxide--a regulator of vascular tone in hypoxia?

Carbon monoxide is a side product of enzymatic degradation of heme--a reaction catalyzed by heme oxygenase (HO). There are three independent molecular forms (isozymes) of heme oxygenase in man. Isoforms HO-2 and HO-3 are constitutive. More detailed studied isoform HO-2 is especially abundant in the human brain. In contrast to isoforms: HO-2 and HO-3, isoform HO-1 is an inducible species of heme oxygenase. Seen in other tissues, expression of HO-1 is also manifested in the endothelium and smooth muscle of blood vessels. Accumulated experimental data indicate more and more clearly on the possible role of endogenous carbon monoxide in cell cytoprotection, and shows it as a probable factor participating in modulation of the vascular tonus in hypoxia.

Carbon Monoxide↗

PubMed2005

Do pancreatic endocrine stem cells exist?

After the transplantation of hearts from female donors into male recipients, cells migrating from the host to the transplanted heart demonstrate the presence of the Y chromosome (up to 18 percent of all cardiomyocytes). Most probably, this kind of migration occurs in all transplantations. However, postnatal origins of pancreatic beta-cells remain still controversial. The extensive experiments on mice question the existence of adult pancreatic endocrine stem cells. In our opinion one of the methods to elucidate this still open problem is carrying out the similar investigation in sex-mismatched transplanted pancreas. The finding of the chromosome Y in Langerhans islets taken from a male recipient's pancreas which has been transplanted from a female donor can confirm the existence of pancreatic endocrine stem cells.

Animals↗

PubMed2004

AMP-deaminase from normal and cirrhotic human liver: a comparative study.

AMP-deaminase (EC 3.5.4.6) is an enzyme of nucleotide breakdown involved in regulation of adenine nucleotide pool in mammalian cells. Reaction catalysed by AMP-deaminase constitutes a rate-limiting step in adenine nucleotide catabolism in liver. In this study kinetic and regulatory properties of AMP-deaminase purified from normal and cirrhotic human liver were investigated. In comparison to AMP-deaminase extracted from the normal human liver, AMP-deaminase extracted from the cirrhotic liver was less sensitive towards substrate analogues, and only a very limited response towards pH and adenylate energy charge changes tested for enzyme isolated from this tissue source had been observed. At physiological pH 7.0, in the absence and in the presence of important allosteric effectors (ATP, ADP, GTP and orthophosphate), AMP-deaminases from the two sources studied manifested different regulatory profiles, with half-saturation constant (S0.5) values being distinctly higher for the enzyme extracted from the pathological organ. In contrast to AMP-deaminase isolated from the normal, healthy liver, where presence of relatively large (68 kDa) protein fragment was also detected, only smaller protein fragments were identified, while SDS-PAG electrophoresis of AMP-deaminase isolated from the cirrhotic liver was performed. The obtained results indicate clearly that advanced proteolytic processes occurring in the cirrhotic liver may affect structural integrity of AMP-deaminase studied, making enzyme less active and less sensitive to regulatory action of important allosteric effectors.

AMP Deaminase↗

PubMed2004

AMP-deaminase from hen stomach smooth muscle--physico-chemical properties of the enzyme.

AMP-deaminase from hen stomach smooth muscle was isolated and physico-chemical properties of the purified enzyme were investigated. The enzyme had an activity optimum at pH 6.5, and poorly deaminated the substrate analogues tested. At optimum pH (6.5), in the absence of regulatory ligands (control conditions), the enzyme manifested hyperbolic substrate-saturation kinetics with half-saturation constant (S(0.5)) of about 4.5 mM. Additions of adenine nucleotide effectors (ATP, ADP) activated the enzyme strongly at all the concentrations tested, diminishing significantly the value of S(0.5) constant. In contrast, the regulatory effect of orthophosphate was variable, and depended on the orthophosphate concentration used. The molecular mass of the enzyme subunit determined in SDS/PAG electrophoresis was about of 37kDa. The obtained results suggest that in different types of hen muscle, similarly as in humans and rats, expression of AMP-deaminase is under the control of independent genes.

AMP Deaminase↗

PubMed2003

Decreased cardiac activity of AMP deaminase in subjects with the AMPD1 mutation--a potential mechanism of protection in heart failure.

OBJECTIVES: Possession of the C34T (Glu12Stop) nonsense mutation in the AMP-deaminase 1 (AMPD1) gene has been shown to be associated with improved prognosis in heart failure and ischemic heart disease. The most likely event leading to these clinical effects is a reduced capacity of the AMP deamination pathway and increased production of cardio-protective adenosine. However, since AMPD1 is predominantly expressed in skeletal muscle, the protective effects could be related not only to local cardiac changes, but also to a systemic mechanism. In the present study we evaluated the effect of the C34T mutation on cardiac AMP-deaminase activity and on the systemic changes in adenosine production. METHODS: The presence of the C34T mutation was assayed by single-stranded conformational polymorphism (SSCP). Analysis of the AMPD1 genotype and measurement of enzyme activities was performed on 27 patients with heart failure (HF). In addition, blood adenosine concentration was measured by liquid chromatography/mass spectrometry (LC/MS) in 21 healthy subjects with established AMPD1 genotype at rest and following exhaustive exercise. RESULTS: Cardiac AMP-deaminase activity in heterozygotes (C/T) was 0.59+/-0.02 nmol/min/g wet wt-about half of the activity found in normal wild-type (C/C) individuals (1.06+/-0.09 nmol/min/g wet wt, P=0.003). There were no significant differences in the activities of any other enzymes between subjects with the C/T or C/C genotype. Resting venous blood adenosine concentration was similar in subjects with C/C, C/T and homozygous for the mutated allele (T/T) genotype. Following exercise, a significant increase in adenosine was observed in T/T subjects (by 0.013+/-0.009 micromol/l, P=0.035) but not in C/C (0.003+/-0.009 micromol/l) or C/T (-0.002+/-0.011 micromol/l). CONCLUSIONS: Our findings indicate that the C34T mutation of AMPD1 leads to a decrease in cardiac enzyme activity of AMP-deaminase without changes in any other adenosine-regulating enzymes, highlighting the importance of local cardiac metabolic changes. Systemic (blood) changes in adenosine concentration were apparent only in homozygous subjects and therefore may play a relatively small part in cardio-protection.

AMP Deaminase↗

PubMed2003

[Lipoproteins HDL and coronary artery disease: a molecular mechanism of fibrate].

The importance of dyslipidemia in the development of cardiovascular disease is now recognized as a central factor of equal, if not greater significance than any other risk factor. Although correction of high level of low-density lipoproteins (LDL) has been regarded now as the main goal of therapy, it has now been reaffirmed that the contribution of low level of high-density lipoproteins (HDL) to the risk of ischaemic heart disease should also be considered. In the therapy of dislipidemias with hipertriglyceridemia and decreased level of HDL lipoprotein fibrates play an especially important role. In the article the molecular mechanism of fibrates action is presented.

Bezafibrate↗

PubMed2003

[Myoadenylate deaminase deficiency among patients with myasthenia gravis--preliminary results of exercise].

Myasthenia Gravis (MG) is a primary disorder of neuromuscular transmission, and patients suffering from this disease manifest specific, progressive weakness of several groups of skeletal muscles. Myoadenylate deaminase deficiency (MADD) is an inborn disease of skeletal muscles, the clinical symptoms of which may mimic symptoms observed in MG. Preliminary results of studies presented in this paper suggest that simultaneous occurrence of MG and MADD may modify energetic metabolism of skeletal muscle.

AMP Deaminase↗

PubMed2002

[The other face of statins].

Clinical studies indicate that treatment with statins significantly reduces the incidence of myocardial infarction and death from cardiovascular diseases. Quite recently statins were found to exert a direct cardiovascular effect, which is independent on their well-known cholesterol lowering action. In this article current views on the role of statins in improvement of function of vascular endothelium are presented.

Anticholesteremic Agents↗