1,721,304 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
Hyperuricemia and cardiovascular diseases: from phylogenesys to patogenetic mechanisms
No full textDuring human evolution, the accumulation of loss of function mutations of the uricase gene led progressively to the lack of the ability to metabolize uric acid into further end-products. Consequently, serum uric acid levels progressively increased over time along with the dietary availability of purine-rich foods. At first, the increase in uricemia contributed positively to primate development by increasing the antioxidant power of the organism, favouring an increase in blood pressure and lipid metabolism. However, later, these positive effects have been overcome by more dangerous consequences. In fact, in the recent period of human being history, the impact of dietary changes on uricemia was so significant that pathological consequences such as gout or renal stones appeared. Furthermore, it has been proved that abnormal uric acid level induces endothelial dysfunction and renal fibrosis. The shift between positive and negative consequences secondary to uric acid is clearly in accordance with the J curve shaped relation that describes the correlation between mortality and serum uric acid level
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