MATERNAL LEUKOCYTE ENZYMES IN HUMAN FETAL MALNUTRITION

The impaired activity of maternal leukocyte pyruvate kinase and its response to allosteric modulators may be a cause and an indicator of fetal malnutrition.     

Effects of inhibition of glycolysis on calcium homeostasis and functional recovery of stunned myocardium

ＥｆｆｅｃｔｓｏｆｉｎｈｉｂｉｔｉｏｎｏｆｇｌｙｃｏｌｙｓｉｓｏｎｃａｌｃｉｕｍｈｏｍｅｏｓｔａｓｉｓａｎｄｆｕｎｃｔｉｏｎａｌｒｅｃｏｖｅｒｙｏｆｓｔｕｎｎｅｄｍｙｏｃａｒｄｉｕｍＧｕｏＷｅｎｙｉ（郭文怡）；ＯｕＪｉｎｘｉ（区晋禧）；ＪｉａＧｕｏｌ...     

Thiamine corrects delayed replication and decreases production of lactate and advanced glycation end-products in bovine retinal and human umbilical vein endothelial cells cultured under high glucose conditions

Summary This study aimed at verifying whether thiamine, a co-enzyme which decreases intracellular glycolysis metabolites by allowing pyruvate and glyceraldheyde 3-phosphate to enter the Krebs cycle and the pentose-phosphate shunt, respectively, corrects delayed replication caused by high glucose concentrations in cultured human umbilical vein (HUVEC) and bovine retinal endothelial cells (BREC). After incubation in physiological (5.6 mmol/l) or high (28.0 mmol/l) glucose with or without 150 μmol/l thiamine, cells were counted and proliferation assessed by mitochondrial dehydrogenase activity. Lactate was measured in both cell types as an index of glycolytic activity and fluorescent advanced glycosylation end-products (AGE) concentration was determined in the HUVEC lysate. Both cell counts and proliferation assays in either of the cell types confirmed the impairment to cell replication induced by high glucose. When thiamine was added to cells kept under high glucose conditions, the number of surviving cells was significantly increased and the reduced cell proliferation appeared to be corrected. Lactate assays confirmed the increased production of this metabolite by BREC and HUVEC in high glucose, which was reduced by thiamine. Fluorescent AGE determination showed that thiamine may prevent non-enzymatic glycation in HUVEC. Thiamine restores cell replication, decreases the glycolytic flux and prevents fluorescent AGE formation in endothelial cells cultured in high glucose, suggesting that abnormal levels of glycolytic metabolite(s) may damage cells. [Diabetologia (1996) 39: 1263–1268] Received: 18 March 1996 and in revised form: 12 June 1996     

Effect of glutathione deprivation on lens metabolism

1-Chloro-2,4-dinitrobenzene (CDNB) was used to conjugate glutathione (GSH) through the catalysis of lens glutathione S-transferase without the untoward oxidative damage to the lens mediated by GSH oxidants. A 2 hr treatment of the rat lens with 1 mM CDNB resulted in a nearly total depletion of lens GSH with neither formation of GSSG nor glutathione-protein mixed disulfides. Rubidium uptake was found to decrease linearly with the loss of GSH; nevertheless, ionic imbalance did not commence until more than 30% cation pump activity was lost. Glycolytic rate dropped following CDNB treatment, due probably to a decline in demand for ATP by the deactivated cation pump. 31P-NMR studies confirmed the irreversible loss of ATP. CDNB depletion of GSH resulted in a two-fold increase in 14CO2 production from [14C]-1-glucose. Whereas oxidative stress resulted in a six-fold increase in glucose utilization through the hexose monophosphate shunt (HMPS), CDNB-treated lenses showed no such stimulation. This indicated that the residual GSH following CDNB treatment was insufficient for the activation of the glutathione peroxidase-reductase-HMPS mechanism and raised the possibility that the increased glucose utilization might be due to mechanisms other than the HMPS. These results indicate an intimate correlation between the GSH content and major metabolic functions in the lens.     

乳酸阈强度下探讨无氧阈机制的人体与动物实验研究

目的:分别通过人体和动物实验探讨乳酸阈强度下代谢转变的机制。方法:选取24名体育专业学生作为人体组,进行递增负荷功率自行车运动;选取30只SD大鼠作为大鼠组,进行递增负荷游泳运动。首先确定两组受试各自的乳酸阈强度,后在不吸氧与补充吸氧条件下按相同运动方案进行递增负荷运动至乳酸阈强度,分别于运动前和乳酸阈强度下测定人体组及大鼠组静脉血氧分压、丙酮酸和乳酸含量。结果:(1)人体组和大鼠组在乳酸阈强度下,氧分压平均值分别是33.55±6.49mmHg(不吸氧)、31.86±6.23mmHg(补充吸氧)和58.64±2.01mmHg(不吸氧)、54.82±7.27mmHg(补充吸氧);血乳酸平均值分别是3.61±0.56mmol/L(不吸氧)、3.72±0.58mmol/L(补充吸氧)和5.43±0.55mmol/L(不吸氧)、5.35±0.50mmol/L(补充吸氧)。人体组和大鼠组运动前及乳酸阈强度下,丙酮酸平均值分别是0.97±0.17mmol/L、1.04±0.16mmol/L和0.93±0.25mmol/L、0.91±0.37mmol/L。(2)在乳酸阈强度下,不论是否吸氧,人体组和大鼠组血乳酸含量与氧分压之间均不相关,整个测试过程中人体组血氧饱和度均不低于98%;而二者血乳酸与血丙酮酸含量之间均呈高度显著性差异(P<0.001);二者运动前与乳酸阈强度时的血丙酮酸含量均无显著性差异(P>0.05)。结果表明,运动中由有氧向无氧代谢转变时体内不缺氧,本实验结果在整体水平上支持了糖酵解时丙酮酸转变成乳酸入血,以防止其堆积的观点。     

Sources of energy for the brain and susceptibility to audiogenic seizures.

The onset of susceptibility to audiogenic seizures (AGS) coincides with the draining of the ear canal at about 14 to 16 days of age. This is also when the mouse brain has almost attained its maximal size and weight, and also about the time of weaning from the dam's high-fat milk to the beginning of dietary self-sufficiency. During suckling, the brain is primarily dependent on ketone-body utilization as a source for brain energy; weaned mice use glucose. It is suggested that in AGS-prone mice, there may be a developmental lag in the onset of a sufficient rate of glycolysis in brain to provide adequate immediately available energy reserves to last through a brief period of an external-stimulus-induced large energy expediture until energy repletion processes can begin. As a results, ATP levels might fall below an hypothesized lower limit to subserve organized neural activity in some inhibitory area of the brain, resulting in the onset of an AGS.     

Enzyme Activities of Myocardial Energy Metabolism during Prolonged Digoxin Treatment in Rats

Abstract The effect of prolonged digoxin treatment (1 mg/kg day for 8 days) on the activity levels of some enzymes of energy metabolism (phosphofructokinase, lactate dehydrogenase, citrate synthase, succinate dehydrogenase) in rat myocardium was studied. In the control animals receiving the solvent mixture (glycerol: ethanol:water in 1:1:1) a transient decrease in the lactate dehydrogenase and citrate synthase activity levels was observed. In the hearts of digoxin treated rats the level of activity of phosphofructokinase was permanently lowered by the fourth day and the level of activity of citrate synthase permanently increased after the first day of treatment. A transient increase in the activity level of succinate dehydrogenase in the myocardium of digoxin treated animals was seen between days 1 and 6. In this study a permanent decrease in phosphofructokinase and an increase in citrate synthase activity levels in rat heart muscle was noted during prolonged digoxin treatment.     

Net proteolysis in glucose-deprived rat lenses incubated in amino acid-free medium

A study of proteolysis was undertaken in rat lenses cultured in balanced salt solution, without amino acids. When glucose was present, slow loss of amino acids to the medium occurred, but sodium and potassium levels remained normal for at least 48 hr. Lenticular glutathione slowly disappeared, with matching increases of glycine and cysteine in the lens plus medium. Lenticular ATP gradually decreased, with matching increase of free phosphate. Ascorbate decreased steadily during incubation, and lactate loss by diffusion exceeded replacement via glycolysis. Lens taurine decreased steadily, but the total in lens plus medium remained constant. In the absence of glucose, the initial loss of ATP and glutathione were faster and some exchange of sodium and potassium occurred. Starting abruptly after 24 hr, when ATP was depleted, rapid net proteolysis was observed. The quantities of proteogenic amino acids in lens plus medium increased linearly to several times the initial values by 48 hr. Increased lens levels of proteogenic amino acids were accompanied by marked influx of sodium and water. Calcium also increased in the lens. Loss of lens taurine was accelerated and depletion of lactate was faster.The results obtained suggest that disappearance of ATP in glucose-deprived lenses is followed by onset of net proteolysis.