Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:1.1.1.27 (lactate dehydrogenase)
29,211 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The hypothesis that posthypoxic renal injury is mediated by xanthine oxidase-derived oxygen free radical production was tested in an in vitro model of rat proximal tubule epithelial cells in primary culture subjected to 60 min of hypoxia and 30 min of reoxygenation. Hypoxia-reoxygenation-induced injury, measured as lactate dehydrogenase (LDH) release, was 54.0 +/- 7.1%. Inhibition of xanthine oxidase by 10(-4) M allopurinol attenuated injury (LDH release = 35.5 +/- 3.7%; P less than 0.01). Oxypurinol was similarly effective. Alternatively, cells were treated with 50 or 100 microM tungsten to inactivate xanthine oxidase. Tungsten prevented hypoxia-reoxygenation-induced superoxide radical production (basal = 97 +/- 8, hypoxia-reoxygenation = 172 +/- 12, and plus tungsten = 73 +/- 8 nmol/micrograms protein) and attenuated hypoxia-reoxygenation-induced injury (LDH release: basal = 18.8 +/- 3.0%, hypoxia-reoxygenation = 62.0 +/- 4.8%, plus 50 microM tungsten = 24.8 +/- 5.0%, and plus 100 microM tungsten = 6.0 +/- 0.7%). In addition, hypoxia and reoxygenation increased the ratio of xanthine oxidase to total activity (xanthine oxidase + xanthine dehydrogenase) from 73 to 100%. Therefore xanthine oxidase was responsible for hypoxia-reoxygenation-induced superoxide radical formation and hypoxia-reoxygenation-induced injury. Xanthine oxidase is likely to be the major source of oxygen free radicals during renal ischemia and reperfusion.
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PMID:Xanthine oxidase produces O2-. in posthypoxic injury of renal epithelial cells. 132 7

Both glutathione and glycine provide some protection against ischemic renal injury in a variety of experimental models. However, results have been inconsistent and there may also be model heterogeneity. The effects of glutathione, glycine, and alanine in a cell culture model of renal anoxia/reoxygenation injury were tested. When primary cultures of rat proximal tubule epithelial cells were subjected to 60 min of anoxia and 30 min of reoxygenation, glutathione (2 mM) essentially eliminated lethal cell injury as determined by lactate dehydrogenase release. Glycine or alanine, on the other hand, provided only partial protection. Glutamate did not protect, although cysteine did. The glutathione synthesis inhibitor buthionine sulfoximine blocked the protective effect of exogenous glutathione, and the glutathione transport inhibitor probenecid partially blocked glutathione protection. A combination of glycine, glutamate, plus cysteine also protected against anoxia/reoxygenation injury. The studies suggest that both glutathione degradation with intracellular resynthesis and transport of intact glutathione into the cell are involved in the protection afforded by exogenous glutathione. These results are different from those obtained in other experimental models of renal ischemia, such as freshly isolated proximal tubules, because the protective effects of glutathione were not derived solely from glycine generation. These studies also suggest the need for caution in extrapolating results from one model of renal anoxic injury to another.
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PMID:Protective effects of glutathione, glycine, or alanine in an in vitro model of renal anoxia. 162 58

The influence of neutrophils on peritubular capillary permeability and intravascular red blood cell (RBC) aggregation after renal ischemia was studied in anesthetized Sprague-Dawley rats. Intraperitoneal administration of antineutrophil serum (ANS) reduced the number of neutrophils in the blood to 3% of normal. The control group received an equal volume of inactive serum. Renal macromolecular capillary permeability was studied from 1) extravasation of albumin and 2) plasma to lymph transport of plasma proteins and of neutral and negatively charged lactate dehydrogenase (LDH). The net driving force (NDF) for fluid transfer over the peritubular capillary membrane was determined by the micropuncture technique. The intrarenal distributions of neutrophils and RBC were measured by a histochemical method and 51Cr-labeled RBC, respectively. Under preischemic control conditions neither macromolecular permeability nor renal clearance of inulin was affected by ANS. However, the steep increase in the macromolecular transport from plasma to lymph resulting from 45 min of ischemia and reperfusion was blunted by ANS, and preischemic control values were restored after 1 h of recirculation. In the control group the mass transport of plasma proteins increased twofold and that of both neutral and negatively charged LDH fourfold. NDF was equal in the two groups. In the ANS-treated animals the intrarenal neutrophil content was only 2% of the control. Neutrophils were found mainly in the cortex, whereas RBC aggregation was observed only in the renal medulla. It is concluded that neutrophils mediate postischemic capillary leakage. It is suggested that this leakage underlies RBC aggregation and incomplete return of blood flow in the renal medulla after ischemia.
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PMID:Peritubular capillary permeability and intravascular RBC aggregation after ischemia: effects of neutrophils. 233 Sep 69

Recent in vitro studies have suggested that the presence of extracellular acidosis is protective against the development of oxygen-deprivation injury in several tissues. Because cellular Ca accumulation after renal ischemia may represent a major pathogenic event leading to cellular damage, the purpose of the present study was to examine the effect of extracellular acidosis on 45Ca uptake and desaturation in normal and hypoxic isolated rat proximal tubules. At pH 7.4, an increase in 45Ca uptake was observed in proximal tubules after 30 min of hypoxia. In addition, 45Ca desaturation was increased significantly in hypoxic tubules at pH 7.4. The alterations in 45Ca uptake and desaturation in hypoxic tubules at pH 7.4 were accompanied by significant signs of cellular injury as assessed by the amount of lactate dehydrogenase (LDH) released by the tubules at the end of the hypoxic period (22.5% above control tubules, P less than 0.01) as well as in morphological changes consistent with hypoxic cell injury. In contrast, when maintained at pH 6.9 throughout the study, no difference in 45Ca uptake or desaturation was observed between the control and hypoxic tubules; the hypoxic proximal tubules exhibited a smaller increase in LDH release (12.7% above control tubules) and did not develop the morphological changes observed at pH 7.4. Thus, during hypoxia and reoxygenation at pH 7.4, the increased 45Ca uptake may contribute in part to cellular injury in rat proximal tubules.
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PMID:Effect of extracellular acidosis on 45Ca uptake in isolated hypoxic proximal tubules. 337 71

The urinary excretion of four enzymes (alkaline phosphatase: AP, leucine aminopeptidase: LAP, lactate dehydrogenase: LDH, muramidase: M) was measured in unanesthetized adult male Wistar rats within 48 h after either a single injection of mercuric chloride (HgCl2) (0.5-1.0 mg x kg-1), or of gentamicin (2.5-25 mg x kg-1), or of tobramoycin (2.5-25 mg x kg-1), or after 30 min of clamping of both renal arteries. Glomerular filtration rate (GFR), TmPAH, plasma urea, urinary protein and sodium excretion were measured simultaneously. The excretion of AP, LAP and LDH, but not that of M, increased significantly above control levels after renal ischemia or the nephrotoxic agents; the increase was dose-related after HgCl2. GFR was not depressed, but TmPAH decreased after the higher doses of the toxic agents. Though more sensitive for detecting minor grades of acute renal damage than function tests, measurements of urinary enzyme excretion were fraught with large inter-individual variation, and variable time-course of changes in different types of renal damage. Short-term exposure (3 months) to phenylmercuric acetate was associated with a significant decrease of the urinary excretion of AP, and of LAP, and of AP activity measured histochemically in proximal tubular cells.
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PMID:Urinary enzyme excretion and changes in renal functions induced by toxic substances or by renal ischemia in rats. 693 3

The mechanisms responsible for the loss of cell potassium during renal ischemia are poorly understood. The present studies examined the hypothesis that potassium channels are activated as an early response to hypoxia and contribute to potassium loss independent from an inhibition of active K+ uptake. Potassium flux in suspensions of freshly isolated rat proximal tubules was measured using an ion-selective electrode. Exposure of the tubules to hypoxia for only 2.5 min resulted in a rise in the passive leak rate of K+ but no decrease in active K+ uptake. The passive leak of K+ was associated with a 40% decrease in cell ATP content. The passive K+ efflux was inhibited by 5 mM Ba2+ (95%) and by 15 mM tetraethylammonium (85%) suggesting that K+ channels were the primary route of K+ movement. The effects of K+ channel blockade on the development of hypoxic injury were also examined. Tetraethylammonium and glibenclamide, an inhibitor of ATP-sensitive K+ channels, reduced hypoxic injury as assessed by the release of lactate dehydrogenase or measurement of DNA damage. These results suggest that activation of K+ channels is an early response to hypoxia and contributes to hypoxic renal injury.
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PMID:Activation of potassium channels contributes to hypoxic injury in proximal tubules. 798 84

Previous studies from our laboratory have demonstrated that postischemic infusion of thyroxin (T4) will augment the restoration of cellular ATP and enhance the recovery of renal function. It has not been clear, however, whether T4 has a direct effect on mitochondrial ATP synthesis or an indirect effect by stabilization of the plasma membrane. To differentiate these putative effects, rats were subjected to 45 min of renal ischemia and given either normal saline (0.5 mL) or T4 (20 micrograms/100 g body weight) during the first 15 min of reflow. Cellular ATP levels were assessed by 31P-nuclear magnetic resonance spectroscopy, and release of lactate dehydrogenase (LDH) was used as an index of plasma membrane integrity at 30 and 120 min of reflow. In rats given normal saline, renal ATP had returned to only 57.9 +/- 1.4% of preischemic values at 30 min of reflow and 66.1 +/- 1.4% by 120 min. LDH release was 13 +/- 0.89% at 30 min and 14.6 +/- 1.6% at 120 min. In contrast, T4-treated animals had ATP levels of 70.2 +/- 2.0% at 30 min and 84.0 +/- 1.9% at 120 min, whereas LDH release was elevated to values similar to those in normal saline-treated rats, 14.9 +/- 1.5% and 14.4 +/- 0.5% at 30 min and 120 min, respectively (nonischemic LDH 8.8 +/- 0.8%). These data suggest that T4 stimulates the recovery of renal ATP by a direct effect on synthesis rather than an indirect effect related to global improvement in cellular integrity.
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PMID:Disassociation of postischemic recovery of renal adenosine triphosphate and cellular integrity. 837 18

Iron-dependent free radical reactions and renal ischemia are believed to be critical mediators of myohemoglobinuric acute renal failure. Thus, this study assessed whether catalytic iron exacerbates O2 deprivation-induced proximal tubular injury, thereby providing an insight into this form of renal failure. Isolated rat proximal tubular segments (PTS) were subjected to either hypoxia/reoxygenation (H/R: 27:15 min), "chemical anoxia" (antimycin A; 7.5 microM x 45 min), or continuous oxygenated incubation +/- ferrous (Fe2+) or ferric (Fe3+) iron addition. Cell injury (% lactic dehydrogenase [LDH] release), lipid peroxidation (malondialdehyde, [MDA]), and ATP depletion were assessed. Under oxygenated conditions, Fe2+ and Fe3+ each raised MDA (approximately 7-10x) and decreased ATP (approximately 25%). Fe2+, but not Fe3+, caused LDH release (31 +/- 2%). During hypoxia, Fe2+ and Fe3+ worsened ATP depletion; however, each decreased LDH release (approximately 31 to approximately 22%; P < 0.01). Fe(2+)-mediated protection was negated during reoxygenation because Fe2+ exerted its intrinsic cytotoxic effect (LDH release: Fe2+ alone, 31 +/- 2%; H/R 36 +/- 2%; H/R + Fe2+, 41 +/- 2%). However, Fe(3+)-mediated protection persisted throughout reoxygenation because it induced no direct cytotoxicity (H/R, 39 +/- 2%; H/R + Fe3+, 25 +/- 2%; P < 0.002). Fe3+ also decreased antimycin toxicity (41 +/- 4 vs. 25 +/- 3%; P < 0.001) despite inducing marked lipid peroxidation and without affecting ATP. These results indicate that catalytic iron can mitigate, rather than exacerbate, O2 deprivation/reoxygenation PTS injury.
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PMID:Inorganic iron effects on in vitro hypoxic proximal renal tubular cell injury. 843 70

We present a 72-year-old man who had episodes of severe, acute renal failure during severe attacks of diarrhea caused by Vibrio cholerae. Patterns of acute tubular necrosis and tubulointerstitial nephritis developed following hypotension and decrease in renal blood flow, causing secondary renal ischemia. There was severe dehydration with profound hypovolemia and infection. The clinical picture included fever, weakness, arthralgia, pedal edema, mild bilateral pleural effusions, anemia, leukocytosis, azotemia with a maximum of 330 mg/dl of urea, creatine to a maximum of 9.8 mg/dl, hypoproteinemia, severe metabolic acidosis, marked increase in lactate dehydrogenase (LDH) and creatine phosphokinase (CPK), microscopic hematuria, sterile leukocyturia, normoglycemic glucosuria and phosphaturia with diminished tubular reabsorption of phosphorus. A short oliguric phase was followed by a polyuric phase lasting about 10 days, and glomerular and tubular function became normal after about 3 weeks. Treatment was by intensive infusions of fluids, electrolytes, sodium bicarbonate, salt-free albumin and antibiotics. To the best of our knowledge, this renal complication of cholera has not yet been described in Israel.
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PMID:[Acute renal failure as a complication of cholera]. 868 55

The 72-kDa heat stress protein (HSP-72) is an inducible cytoprotectant protein. Although transient renal ischemia in vivo induces HSP-72, it is not known whether prior heat stress protects renal epithelial cells from injury mediated by ATP depletion. To evaluate this hypothesis, opossum kidney (OK) cells were exposed to sodium cyanide and 2-deoxy-D-glucose in the absence of medium glucose, a maneuver that reduced cell ATP content to < 10% of the control value within 10 min and decreased cell survival. One day after 2 h of ATP depletion, OK cells previously exposed to heat stress (to induce accumulation of HSP-72) exhibited marked improvement in survival (a > 4-fold increase in total DNA), less uptake of vital dye, and less release of lactate dehydrogenase (LDH) than cells subjected to ATP depletion alone (23.0 +/- 1.6 vs. 34.1 +/- 1.2% of total LDH, respectively). Enhanced clonogenicity post-heat stress was completely prevented by cycloheximide and positively correlated with the steady-state content of HSP-72. In the recovery period after ATP depletion, cell ATP content, maximum mitochondrial ATP production rate, and total LDH activity were all significantly higher in cells with abundant HSP-72. Although the protective effects associated with heat stress are likely to be multifactoral, preserved cell metabolism and higher ATP content could enhance cellular repair processes after ATP depletion.
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PMID:Prior heat stress enhances survival of renal epithelial cells after ATP depletion. 876 25


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