Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Renal ischemia causes a reversible loss of microvillar membrane (MVM) of the proximal tubule cell and of MVM enzyme specific activities (S.A.). We sought to determine if recovery of the MVM glycoprotein was accomplished through de novo synthesis or recycling. Renal ischemia (25 min) was induced in rats by occlusion of the left renal artery, followed by 15 min or 4 hrs of reflow of blood. Radiolabelled fucose was injected into rats before or after ischemia and was used as a marker for new glycoprotein synthesis or recycling of prelabelled glycoprotein. Ischemia, followed by 15 min of reflow, caused a 49% reduction in protein associated with the isolated MVM fraction of the ischemic kidney. There was also a decrease in newly fucosylated glycoprotein in both homogenate and MVM fraction measured as S.A. or total amount of labeled glycoprotein. Pre-labelled glycoproteins had no change in S.A. in homogenates or MVM fractions of ischemic or contralateral kidneys. However, the total amount of labeled glycoprotein in the ischemic MVM fraction was reduced. At 4 hrs of reflow, protein content of the MVM fraction was back to normal. Pre-labelled glycoproteins of the ischemic homogenate and MVM fraction were also back to normal with no significant dilution of glycoprotein S.A. by newly synthesized protein, indicating that glycoprotein recycling occurs to a large extent in the ischemic kidney.
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PMID:Glycoprotein reutilization in regenerating microvilli after renal ischemia in rats. 406 83

Tissue sections of kidneys from 172 patients with various pathologic conditions, such as hydronephrosis, interstitial nephropathies, ischemia, chronic graft rejection and renal cancer, were evaluated by an image analysis technique. Structurally defined kidney alterations were monitored for enzymatic, immunologic and other histochemical changes. Indicator enzymes of the proximal tubule, alanine-aminopeptidase (AAP), alkaline phosphatase (AP), beta-glucoronidase (beta-Gl) and gamma-glutamyltranspeptidase (GGTP), were used as parameters for screening. Enzyme concentrations were found to be significantly decreased in kidney sections of patients with various renal diseases (AP less than 15%, AAP less than 55% and beta-Gl less than 60%) as compared to normal kidney tissues (100%). AAP concentration was measured quantitatively by specific immunofluorescence using an antienzyme antibody. Immunofluorescence of AAP was comparable to that of AAP calculated by the colorimetric technique (substrate: DL-alanine-beta-naphthylamide-HCl) and decreased to less than 50% in altered kidney tissues. Furthermore, kidney cancer (less than 20%) and kidney tissue adjacent to tumours (less than 65%) displayed significantly decreased levels of kidney marker enzyme activity. This study suggests that (1) the diseased kidney is characterized by a defined change in key enzymes of the cell surface and (2) renal cancer exhibits partial depletion of these constituents. Image analysis of the pattern of enzyme activity appears to be a useful tool in the analysis of renal pathology.
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PMID:Quantitative enzymatic, immunologic and histochemical studies of clinically relevant human kidney alterations using image analysis. 611 96

Fluid (sodium) reabsorption, total glucose efflux, and reabsorption of angiotensin II and insulin from the proximal convoluted tubule were studied in rats by in vivo microperfusion. After 35 min of total renal artery occlusion, function was assessed at two intervals, 0-1 h (early recovery, ER) and 2-4 h (late recovery, LR). Light and electron microscopic evaluation showed 60-75% loss of proximal convoluted tubule brush border membrane in ER and nearly complete restoration of brush border in LR. No other structural abnormalities were evident. Renal blood flow was unchanged from control during both ER and LR. During ER, fluid reabsorption was reduced to 29.8 +/- 5.2%, and total glucose efflux, at normal tubule loads, to 73.9 +/- 5.5% of control. However, angiotensin II and insulin reabsorption were unchanged. In LR, fluid reabsorption remained significantly reduced at 54.3 +/- 8.1% of control. Total glucose efflux from the proximal tubule was normal in LR at glucose loads of up to 400 pmol X min-1, but was significantly reduced at higher loads. Passive glucose efflux, measured in the presence of 10(-4)M phloridzin, was not altered by ischemia. Brief ischemia results in significant alterations in proximal tubular reabsorption of sodium and glucose, which correlate with a substantial loss of brush border during ER. However, despite restoration of cell morphology to normal in LR, transport defects for both sodium and glucose persist.
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PMID:Recovery of proximal tubular function from ischemic injury. 636 44

Renal cortex was studied during experimentally induced ischemia. A transient increase in anerobic glycolysis occurred with concomitant swelling of both the Golgi apparatus and mitochondria. These intracytoplasmic organelles underwent marked changes in their intracellular positions. Infolding of cytoplasmic membrane at the basal side of proximal tubule cells increased in complexity and proceeded to enclose various intracytoplasmic microorganelles such as mitochondria and the Golgi apparatus. Piling up in layers was particularly marked around mitochondria. This piling up appeared as myelin-like structures on the free surface of, and within, proximal tubule cells, and followed disruption of the brush border at the free surface. Histological examination of thin sections showed that the fused portions of this brush border were actually brush border cytoplasmic membrane piled up in layers giving the appearance of myelin-like structures. After two hours of ischemia, parts of the membrane of these myelin-like structures were disrupted. Large vacuoles developed and these were thought to be related to the large vacuoles seen during cell degeneration.
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PMID:Myelin-like structures seen intracellularly in renal tubule cells subjected to ischemia. 644 36

Left kidneys of rats were made ischemic for 25 minutes and proximal tubule brush border alterations studied in the S1 and S2 segments. Scanning electron microscopy revealed that brush border microvilli became unstable, fused with one another, and were interiorized into proximal tubule cytoplasm soon after reflow of blood following ischemia. Rapid regeneration followed; scanning electron microscopy showed that regeneration occurred in a fashion whereby clusters of microvilli in flower-like configurations were extruded from the cell interior toward the surface. Such unique patterns of microvillus formation have not been reported before. Activity of the brush border enzymes, alkaline phosphatase and maltase, were not significantly depressed throughout the cycle of brush border loss and regeneration. Likewise, there were no alterations in the activity of beta-glucuronidase, a lysosomal enzyme. Alkaline phosphatase cytochemistry showed that microvillus membranes that were interiorized into the cell cytoplasm retained enzyme activity on their surfaces during the early period of brush border loss as well as during regeneration. These results strongly suggest that in reversibly injured proximal tubule cells regeneration of the brush border occurs primarily by a process of recycling of damaged, previously incorporated membrane. The nature of the initial membrane damage and the mechanism of recycling remain unknown.
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PMID:Mechanism of proximal tubule brush border loss and regeneration following mild renal ischemia. 730 Feb 48

Upon exposure to a transient ischemia, the distal tubule of the kidney often escapes the severe damage which afflicts the proximal tubule. To ascertain whether this feature of the distal tubule is attributable to its intrinsic cellular properties, we focused on two pairs of unique tubule segments; distal versus proximal convoluted tubules in the superficial cortex and distal versus proximal straight tubules in the outer stripe of the outer medulla. These tubules were chosen because, firstly, they can be identified by morphology and immunostaining, and secondly, each pair has the same anatomical relationship to the circulation. Detailed morphometric analyses were performed six hours following unilateral transient ischemia in adult rats to semiquantitate the local tissue damage in these specific nephron segments. The architecture of the distal convoluted and straight tubules was remarkably well preserved, contrasting to the moderate to extensive necrotic changes seen in the proximal tubules. In search of the potential intrinsic cellular mechanism that underlies the observed difference, we examined the segmental distribution along the nephron of manganese superoxide dismutase gene transcripts by in situ hybridization. This antioxidant enzyme gene was expressed primarily in the distal tubules with contrastingly low levels of expression in the proximal tubules. Moreover, following ischemia-reperfusion, this distal tubule-dominant pattern was further accentuated immediately following reperfusion. The study indicates that the marked difference between the proximal and distal tubules in their susceptibility to injury in vivo is attributable to their intrinsic cellular properties, which include the local level of antioxidants.
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PMID:Strategic locus for the activation of the superoxide dismutase gene in the nephron. 753 59

Previous studies have suggested that EGF or other members of the EGF family of mitogenic proteins are involved in proliferation of renal tubular epithelial cells occurring during recovery from injury to the kidney. The present studies examined whether expression of mRNA for the recently identified heparin-binding EGF-like growth factor (HB-EGF) is regulated in response to renal injury induced by either ischemia/reperfusion or mercuric chloride. Increased expression of HB-EGF mRNA was demonstrated in the post-ischemic kidney within 45 min of unilateral ischemia/reperfusion in the rat. Induction of HB-EGF mRNA occurred only when ischemia was followed by reperfusion, and was not eliminated by removal of blood cells from the post-ischemic kidney by saline perfusion. In situ hybridization with 35S-labeled antisense riboprobes of HB-EGF indicated that compared with control, there was increased HB-EGF mRNA expression in the 6 h post-ischemic kidney in the inner cortex and outer medulla in a patchy distribution, with the greatest expression in the inner stripe of the outer medulla. Expression occurred primarily in tubular epithelial cells. Recombinant human HB-EGF stimulated [3H]-thymidine incorporation in both primary cultures of rabbit proximal tubule cells and NRK 52E normal rat kidney epithelial cells, with potency similar to that of EGF. Induction of HB-EGF mRNA was observed in tubules freshly isolated from rat renal cortex or outer medulla when the tubules were subjected to reoxygenation after incubation in anoxic conditions. The nephrotoxin, mercuric chloride, also caused induction of HB-EGF mRNA both in vivo and in isolated rat cortical tubules. The anoxia/reoxygenation-induced expression of HB-EGF mRNA in isolated tubules was inhibited by the free radical scavengers, di- and tetra-methylthiourea, indicating involvement of reactive oxygen species. These findings indicate that HB-EGF mRNA is inducible in the kidney in vivo by acute tubular injury and suggest that HB-EGF may act as an autocrine/paracrine growth factor involved in proliferation of tubular epithelial cells and repair of the kidney.
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PMID:Induction of heparin-binding epidermal growth factor-like growth factor mRNA in rat kidney after acute injury. 763 38

Ischemia results in alterations in the integrity of the plasma membrane of renal epithelial cells, changes in cell polarity, and initiation of cell division. Because microtubules are implicated in these processes, we examined the effects of ischemia and reperfusion on the microtubular cytoskeleton in rat kidney. Major alterations in the microtubule network of S3 proximal tubules were detected after 40 min of ischemia followed by 1 h of reperfusion. There was fragmentation of microtubules and considerably less intense staining with antitubulin antibodies than with normal kidneys. Some thick ascending limbs of Henle close to medullary vascular bundles showed a variable loss of tubulin staining. After 24 and 48 h of reperfusion, tubulin labeling was again present in most proximal tubule cells in contact with the basement membrane but was not detectable in exfoliated cells. Numerous mitotic figures were present in kidneys 48 h after reperfusion. Kidneys subjected to 40 min of ischemia without reperfusion and contralateral kidneys studied after 1 h of reperfusion showed only mild microtubular disruption. Because of the established role of microtubules in the generation and maintenance of epithelial cell polarity, their loss may contribute to structural changes that occur after ischemia and reperfusion.
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PMID:The microtubule network of renal epithelial cells is disrupted by ischemia and reperfusion. 781 Jul 5

L-type Ca2+ channel blockers (CCBs) have been shown to be protective against ischemia-induced injury of the kidney, suggesting that increased intracellular Ca2+ levels ([Ca2+]i) play an important role in the pathogenesis of ischemic cell injury. To assess the role of [Ca2+]i in anoxic injury of the proximal tubule (PT) and the protective effect of CCBs, digital imaging fluorescence microscopy was used to monitor [Ca2+]i in individual PT cells during 60 minutes of anoxia. [Ca2+]i started to rise within 10 minutes and reached maximal levels between 30 to 45 minutes of anoxia. The onset of this increase and the maximal levels reached varied markedly among individual cells. The mean values for initial and maximal anoxic [Ca2+]i were 109 +/- 2 (N = 209) and 422 +/- 14 (N = 240) nM, respectively. Methoxyverapamil (D600; 1 microM) significantly reduced anoxic [Ca2+]i to 122 +/- 5 nM (P < 0.05; N = 79). Removal of extracellular Ca2+ completely abolished anoxia-induced increases in [Ca2+]i, confirming that these increases in [Ca2+]i result from Ca2+ influx. During 60 minutes of anoxia, PT cells showed a gradual decrease in cell viability to 54 +/- 2%. D600 (1 microM) significantly increased cell viability to 64 +/- 3% (P < 0.05). Glycine (5 mM), however, increased cell viability to 77 +/- 4% without a significant reduction in anoxic [Ca2+]i levels. Low Ca2+ medium only protected when 0.1 mM La3+ was included, a condition which increased cell viability to 82 +/- 5%.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of Ca2+ channel blockers, low Ca2+ medium and glycine on cell Ca2+ and injury in anoxic rabbit proximal tubules. 793 41

The present study was performed in vivo in rabbits to evaluate the functional and morphologic effects of verapamil in a model of ischemic acute renal failure (ARF). Particularly impressive was the ultrastructural integrity of renal tubules in the animals exposed to both ischemia and verapamil. Three groups were studied: Group A: no ischemia; Group B: renal ischemia alone; and Group C: renal ischemia with verapamil. Creatinine clearance was higher in Group C (0.77 mL/min/kg) compared to Group B (0.13 mL/min/kg) at 24 h of reperfusion (p < .005) as well as at 48 and 72 h (0.73 mL/min/kg) vs. 0.35 mL/min/kg; p < .05 and 0.90 mL/min/kg vs. 0.46 mL/min/kg; p < 0.05, respectively). Light microscopic evaluation of Group C rabbits revealed significantly better preservation of proximal tubule (PT) brush border (p < .0005) and less desquamation of PT (p < .05) compared to Group B. Ultrastructural examination of in vivo perfused kidneys also demonstrated decreased loss of microvilli of PT (p < .0005) as well as less cellular edema (p < .005), fewer cells with apical PT membrane rupture (p < .01), better preservation of mitochondria (p < .005), less flattening of the PT basolateral labyrinth (p < .05), and fewer hypertrophic actin bands at the basal surface of PT epithelial cells (p < .05). These results suggest that verapamil markedly attenuates PT morphologic injury in a rabbit model of reversible ischemic ARF. The functional protection observed in these studies may be related, in part, to the improved structural integrity of the renal tubules. Renal transplantation and anticipated renal ischemia (i.e., surgical interventions) are two important situations where treatment with verapamil or other calcium channel blockers may prove to be clinically beneficial.
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PMID:Functional, histologic, and ultrastructural study of the protective effects of verapamil in experimental ischemic acute renal failure in the rabbit. 804 59


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