Expression patterns of AMP-deaminase isozymes in human hepatocellular carcinoma (HCC).

BACKGROUND: AMP-deaminase (EC 3.5.4.6) is an enzyme of nucleotide breakdown involved in regulation of energetic metabolism in mammalian cells. The enzyme is coded by a family of three independent genes (AMPD1, AMPD2 and AMPD3), synthesizing three different isozymes. In mammalian liver, the reaction catalyzed by AMP-deaminase constitutes a rate-limiting step in adenine nucleotide catabolism. In neoplastic liver, adenine nucleotide catabolism is a subject of many modifications, which influence the expression of genes synthesizing enzymes regulating this pathway. AIMS: The experimental studies presented here illustrate the expression of AMPD genes in human liver neoplasm tumor (HCC, hepatocellular carcinoma). METHODS: RT-PCR and Western blotting methods were used for determining of the goal mentioned above. RESULTS AND CONCLUSION: Expression level of AMPD gene family in the tumorous fragment (HCC tumor) of neoplastic liver did not differ substantially from that found in the nontumorous (cirrhotic) fragment of the organ. In this case the expression of AMPD2 gene was prevailing. AMPD2 was the main isoform of AMP-deaminase identified in two liver fragments compared. This is a first report evidencing the pattern of AMPD genes expression in neoplastic human liver.

[Family of AMP-deaminase genes]. / Rodzina genów deaminazy AMP.

AMP-deaminase (AMP-aminohydrolase, EC 3.5.4.6), a highly regulated oligomeric enzyme catalyzing the irreversible deamination of adenylic acid (5'-AMP), is located at a branch point of adenylate nucleotide catabolism. It plays an important role in the stabilization of adenylate energy charge (AEC) and the regulation of the purine nucleotide pool in several types of animal tissue. Tissue- and stage-specific isoforms of AMP-deaminase were described in mammals. In humans, three isozymes of AMP-deaminase, i.e. M (muscle), L (liver), and E (erythrocyte), exhibiting different physical, catalytic, and regulatory properties, were identified. AMP-deaminase activity is encoded by a multigene family in which two genes produce at least three mRNAs through alternative splicing of one of the primary transcripts. In this study we present all found and so far unpublished detailed knowledge about AMP-deaminase gene structures. We also present basic information on the effects of these gene mutations.

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.

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.

[The other face of statins]. / Drugie oblicze statyn.

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.