1,721,078 research outputs found
Low hydrogen sulphide and chronic kidney disease: A dangerous liaison
No full textHydrogen sulphide, H(2)S, is a gaseous compound involved in a number of biological responses, e.g. blood pressure, vascular function and energy metabolism. In particular, H(2)S is able to lower blood pressure, protect from injury in models of ischaemia-reperfusion and induce a hypometabolic state. In chronic kidney disease (CKD), low plasma hydrogen sulphide levels have been established in humans and in animal models. The enzymes involved in its production are cystathionine β-synthase, cystathionine γ-lyase and 3-mercaptopyruvate sulphurtransferase. The mechanisms for H(2)S decrease in CKD are related to the reduced gene expression (demonstrated in uraemic patient blood cells) and decreased protein levels (in tissues such as liver, kidney, brain in a CKD rat model). In the present Nephrol Dial Transplant issue, in fact, Aminzadeh and Vaziri document that the alterations in this pathway complicate the uraemic state and are linked to CKD progression. They furnish a time frame in CKD and record enzyme tissue distribution. It remains to be established if low H(2)S is causally linked to CKD progression and if interventions aimed to restore the status quo ante are able to modify this picture.Hydrogen sulphide, H2S, is a gaseous compound involved in a number of biological responses, e.g. blood pressure, vascular function and energy metabolism. In particular, H2S is able to lower blood pressure, protect from injury in models of ischaemia-reperfusion and induce a hypometabolic state. In chronic kidney disease (CKD), low plasma hydrogen sulphide levels have been established in humans and in animal models. The enzymes involved in its production are cystathionine β-synthase, cystathionine γ-lyase and 3-mercaptopyruvate sulphurtransferase. The mechanisms for H2S decrease in CKD are related to the reduced gene expression (demonstrated in uraemic patient blood cells) and decreased protein levels (in tissues such as liver, kidney, brain in a CKD rat model). In the present Nephrol Dial Transplant issue, in fact, Aminzadeh and Vaziri document that the alterations in this pathway complicate the uraemic state and are linked to CKD progression. They furnish a time frame in CKD and record enzyme tissue distribution. It remains to be established if low H2S is causally linked to CKD progression and if interventions aimed to restore the status quo ante are able to modify this picture. © 2011 The Author
Epigenetics in hyperhomocysteinemic states. A special focus on uremia
No full textAim of this article is to review the topic of epigenetic control of gene expression, especially regarding DNA methylation, in chronic kidney disease and uremia. Hyperhomocysteinemia is considered an independent cardiovascular risk factor, although the most recent intervention studies utilizing folic acid are negative. The accumulation of homocysteine in blood leads to an intracellular increase of S-adenosylhomocysteine (AdoHcy), a powerful competitive methyltransferase inhibitor, which is itself considered a predictor of cardiovascular events. The extent of methylation inhibition of each individual methyltransferase depends on the methyl donor S-adenosylmethionine (AdoMet) availability, on the [AdoMet]/[AdoHcy] ratio, and on the individual Km value for AdoMet and Ki for AdoHcy. DNA methyltransferases are among the principal targets of hyperhomocysteinemia, as studies in several cell culture and animal models, as well as in humans, almost unequivocally show. In vivo, DNA methylation may be also influenced by various factors in different tissues, for example by rate of cell growth, folate status, etc. and importantly inflammation. In chronic kidney disease and in uremia, hyperhomocysteinemia is commonly seen, and can be associated with global DNA hypomethylation, and with abnormal allelic expression of genes regulated through methylation. This alteration is susceptible of reversal upon homocysteine-lowering therapy obtained through folate administration. If this abnormality will translate itself in alterations of expression of genes relevant to the pathogenesis of this disease still remains to be established. In addition, these results establish a link between the epigenetic control of gene expression and xenobiotic influences, such as folate therapy. © 2009 Elsevier B.V. All rights reserved
Human erythrocyte D-aspartyl/L-isoaspartyl methyltransferases: enzymes that recognize age-damaged proteins.
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Adverse effects of hyperhomocysteinemia and their management by folic acid
No full textA moderate increase in plasma homocysteine is an independent risk factor for cardiovascular disease. Plasma homocysteine is frequently elevated in chronic renal failure and in uremic patients, and the major causes of death in these patients are cardiovascular accidents. Homocysteine metabolism and mechanisms of toxicity are reviewed. Homocysteine elevation in blood leads to the intracellular increase of its precursor, adenosylhomocysteine, a powerful inhibitor of adenosylmethionine-dependent transmethylations. In vitro evidence shows that this increase is reversible upon homocysteine removal. Membrane protein methylation levels are consistently reduced in erythrocytes of both chronic renal failure and hemodialysis patients. This widespread enzymatic methylation is a key step for the repair of molecular damage resulting from the spontaneous deamidation and isomerization reactions of susceptible residues in proteins. In agreement with these findings is the observation that the concentration of a stable side product, D-Asx, of the repair process is significantly lower in erythrocyte membrane proteins from hemodialysis patients than from controls, showing that the repair of damaged membrane proteins is actually defective. It has been shown that treatment with folates dramatically lowers plasma homocysteine, presumably by improving remethylation to methionine. This indicates that folates and/or their active derivative, i.e., methyltetrahydrofolate, could be effective in ameliorating transmethylations as well
Distinct C-terminal sequences of isozymes I and II of the human erythrocyte L-isoaspartyl/D-aspartyl protein methyltransferase.
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Homocysteine and Hydrogen Sulfide, Two Opposing Aspects in the Pathobiology of Sulfur Compounds in Chronic Renal Failure
No full textSulfur is an element with a plurality of functions, resulting from its numerous oxidation states in which it exists, which gives the emerging compounds a greatly diverse stability. Among these we have homocysteine, an amino acid, and hydrogen sulfide, an inorganic gas, both present in the human body, the former in increased amounts in chronic kidney disease, the latter is instead decreased.1,2 These compounds epitomize two opposites: homocysteine even if not incorporated into proteins, nonetheless binds to them strongly, while hydrogen sulfide is volatile
D-amino acids in aging erythrocytes.
No full textMature human erythrocytes are highly differentiated cells which have lost the ability to biosynthesize proteins de novo. During cell aging in circulation, erythrocyte proteins undergo spontaneous postbiosynthetic modifications, regarded as "protein fatigue" damage, which include formation of isomerized and/or racemized aspartyl residues. These damaged proteins cannot be replaced by new molecules; nevertheless, data support the notion that they can be repaired to a significant extent, through an enzymatic transmethylation reaction. This repair reaction has therefore been used as a means to monitor the increase of altered aspartyl residues in erythrocyte membrane proteins during cell aging. The relationship between protein repair and aspartyl racemization in red blood cell stress and disease is discussed
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