Selma Süer Gökmen

Serum total and lipid-bound sialic acid levels following acute myocardial infarction

Abstract Although serum total sialic acid has been shown to be a cardiovascular risk factor, with elevated levels associated with increased cardiovascular mortality and also with cerebrovascular disease, the reason for the elevation in serum sialic acid content remains obscure. It has been shown that an increased output of serum proteins by the liver due to some type of acute phase reaction may be one of the possible sources of an increased serum sialic acid concentration in patients with myocardial infarction. An increase in the activity of sialidase, which cleaves the terminal sialic acid residues from oligosaccharides, glycoproteins and gangliosides, may also play an important role in the elevation of serum total sialic acid in myocardial infarction. Elevated serum total sialic acid in the blood might result either from the shedding or secreting of sialic acid from the cell membrane surface, or releasing of cellular sialic acid from the cell into the bloodstream due to cell damage after myocardial infarction. The purpose of the present study is to investigate serum total and lipid-bound sialic acid and the enzymes serum lactate dehydrogenase, creatine kinase and aspartate aminotransferase in patients with acute myocardial infarction, at 24 h post-infarction (day 1), 48 h post-infarction (day 2) and 72 h post-infarction (day 3). A possible role of cell damage in the elevation of serum total and lipid-bound sialic acid levels in these patients was also evaluated. In this study, 40 patients with myocardial infarction ranging in age from 42 to 68 years, and 26 healthy volunteers ranging in age from 45 to 71 years were included. Serum total sialic acid determination was carried out by the thiobarbituric acid method of Warren and lipid-bound sialic acid by the method of Katopodis. Our data shows that a) there is a gradual increase in the levels of serum total sialic acid and lipid-bound sialic acid during the first three days after the acute myocardial infarction and b) the elevation in serum total sialic acid levels correlates with the elevation in lactate dehydrogenase activity only on day 1 following infarction. Therefore, either the shedding or secreting of sialic acid from the cell or cell membrane surface may be partly responsible for an increased serum sialic acid concentration especially on day 1 following myocardial infarction.

Relationship between serum sialic acids, sialic acid-rich inflammation-sensitive proteins and cell damage in patients with acute myocardial infarction

Abstract The role of sialic acid (SA) in the pathogenesis of atherosclerosis and as a predictor of cardiovascular events has attracted much attention in recent years. However, most studies investigating the role of total and lipid-bound sialic acids (TSA and LSA) in the pathogenesis of atherosclerosis lack information on the reason for the elevated SA concentrations in coronary heart disease and myocardial infarction. Since the inflammation-sensitive proteins are glycoproteins with SA residues, an increase in their levels due to some type of acute-phase reaction or inflammation could be responsible for the elevated TSA levels in acute myocardial infarction (AMI). Elevated serum SA levels might also be due to either shedding or secretion of free SA from the cell or cell membrane surface if neuraminidase levels are increased, or to the release of cellular SA-containing glycolipids and/or glycoproteins into plasma from myocardial cells after AMI. The aim of the present study was to investigate both the possible role of SA-rich inflammation-sensitive proteins and the cell damage due to elevated serum TSA levels in AMI. A possible role of serum LSA as an indicator of the shedding or secretion of SA from the cell or cell membrane surface in AMI was also evaluated. The study included 38 subjects with AMI and 32 healthy volunteers. Serum TSA and LSA were determined using the methods of Warren and Katopodis, respectively. The concentrations of serum SA-rich inflammation-sensitive proteins, namely α1-antitrypsin, α2-macroglobulin and ceruloplasmin were determined immunoturbidimetrically. Our data showed that: a) mean levels of serum TSA and LSA and SA-rich inflammation-sensitive proteins in patients with AMI were significantly increased; and b) there was a significant positive correlation between TSA and LSA and α1-antitrypsin in patients with AMI. Since the transfer of free SA to lipoproteins is required for an increase in serum LSA levels, and free SA for this transfer can be provided by the secretion of SA from the cell, it is obvious that the shedding or secretion of SA from the cell membrane surface or release of cellular SA from cells into the bloodstream due to cell damage after AMI also occur after AMI. As a result, we can report that either the shedding or secretion of SA from the cell or cell membrane surface and the increased output of SA-rich inflammation-sensitive proteins may together be responsible for the elevated TSA levels in AMI.

Caffeine Increases Apolipoprotein A-1 and Paraoxonase-1 but not Paraoxonase-3 Protein Levels in Human-Derived Liver (HepG2) Cells

Background: Apolipoprotein A-1, paraoxonase-1 and paraoxonase-3 are antioxidant and anti-atherosclerotic structural high-density lipoprotein proteins that are mainly synthesized by the liver. No study has ever been performed to specifically examine the effects of caffeine on paraoxonase enzymes and on liver apolipoprotein A-1 protein levels. Aims: To investigate the dose-dependent effects of caffeine on liver apolipoprotein A-1, paraoxonase-1 and paraoxonase-3 protein levels. Study Design: In vitro experimental study. Methods: HepG2 cells were incubated with 0 (control), 10, 50 and 200 μM of caffeine for 24 hours. Cell viability was evaluated by 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay. Apolipoprotein A-1, paraoxonase-1 and paraoxonase-3 protein levels were measured by western blotting. Results: We observed a significant increase on apolipoprotein A-1 and paraoxonase-1 protein levels in the cells incubated with 50 µM of caffeine and a significant increase on paraoxonase-1 protein level in the cells incubated with 200 µM of caffeine. Conclusion: Our study showed that caffeine does not change paraoxonase-3 protein level, but the higher doses used in our study do cause an increase in both apolipoprotein A-1 and paraoxonase-1 protein levels in liver cells.

Effect of Lipoic Acid on Serum Paraoxonase-1 and Paraoxonase-3 Protein Levels and Activities in Diabetic Rats

The aim of the present study was to investigate the effect of streptozotocin-induced diabetes mellitus and lipoic acid treatment on serum paraoxonase-1 and paraoxonase-3 protein levels and paraoxonase, arylesterase and lactonase activities.36 rats were equally and randomly divided into 4 groups as control, lipoic acid, diabetes and diabetes+lipoic acid. To induce diabetes, a single dose of streptozotocin (40 mg/kg) was injected intraperitoneally to diabetes and diabetes+lipoic acid groups. Lipoic acid (10 mg/kg/day) was injected intraperitoneally for 14 days to lipoic acid and diabetes+lipoic acid groups. Serum PON1 and PON3 protein levels were measured by western blotting. Serum paraoxonase, arylesterase and lactonase activities were determined by the measuring initial rate of substrate (paraoxon, phenylacetate and dihydrocoumarin) hydrolysis.Streptozotocin-induced diabetes mellitus caused a significant decrease whereas lipoic acid treatment caused a significant increase in serum PON1 and PON3 protein levels and paraoxonase, arylesterase and lactonase activities. The increase percent of serum PON3 protein was higher than that of serum PON1 protein and the increase percent of serum lactonase activity was higher than that of serum paraoxonase and arylesterase activities in diabetes+lipoic acid group.We can report that, like PON1 protein, PON3 protein and actually its lactonase activity may also have a role as an antioxidant in diabetes mellitus and lipoic acid treatment may be useful for the prevention of the atherosclerotic complications of diabetes by increasing serum PON1 and PON3 protein levels and serum enzyme activities.