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:3.6.1.3 (ATPase)
65,361 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Immature renal tubules are more tolerant to ischemia than mature renal tubules. Here we compared the developmental pattern for some cellular responses evoked by hypoxia and reoxygenation in renal proximal tubules from 10- and 40-day-old rats. Redistribution of Na(+)-K(+)-ATPase from the plasma membrane was studied by confocal microscopy techniques in primary cultured renal proximal tubular cells. The developmental expression of Na(+)-K(+)-ATPase, micro-calpain and heme oxygenase-1 was measured by RT-PCR techniques in rat renal cortex. In response to hypoxia Na(+)-K(+)-ATPase redistribution from the plasma membrane was almost 2-fold increased in cells isolated from mature kidneys compared with cells isolated from immature kidneys. Reoxygenation resulted in a complete reestablishment of Na(+)-K(+)-ATPase in the plasma membrane in the immature but not in the mature cells. The dissociation of Na(+)-K(+)-ATPase from the plasma membrane was associated with a reduced activity and a reduced expression of Na(+)-K(+)-ATPase in the mature but not in the immature tubular cells. The expression of micro-calpain, a factor shown to induce ischemic injury to proximal tubular cells, was significantly lower in the immature compared with the mature kidney, whereas the expression of heme oxygenase-1, a factor shown to protect from renal ischemic injury, was significantly higher in the immature kidney. The results help to explain the increased tolerance of the immature kidney to injury caused by ischemia and reperfusion.
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PMID:Cellular response to renal hypoxia is different in adolescent and infant rats. 1466 54

The cytosolic calcium concentration in human platelets is elevated by several agonists via receptor-operated mechanisms involving both Ca(2+) release from intracellular stores and Ca(2+) entry. In order to get a mechanistic insight in the effect of carbon monoxide (CO)-containing solutions, this work examines the changes in [Ca(2+)](i) induced by 100 microM adenosine 5'diphosphate (ADP), 0.1 IU/ ml thrombin, 0.5 microM thapsigargin or 0.5 microM ionomycin in human platelets. In a saline solution bubbled with CO, the increase of [Ca(2+)](i) produced by thrombin was 72+/-4% of the response evoked in the control solution (CO-free) and the response elicited by ADP was 64+/-8% of the control. When a mixture of 5% CO/95% N(2) was used, the responses were 70+/-7% of control for thrombin and 79+/-6% of control for ADP. The mobilization of stored calcium produced by thrombin in a calcium-free solution and the increase of [Ca(2+)](i) produced by subsequent introduction of 1 mM extracellular calcium were both reduced in the presence of CO (82+/-6% and 78+/-5% of control, respectively). Similar reductions in the presence of CO were found when platelets were stimulated by ADP (62+/-8% and 60+/-8% for mobilization in calcium-free media and calcium entry, respectively). Although the change in [Ca(2+)](i) induced by ionomycin in the presence of extracellular calcium was almost the same in the absence or presence of CO (97+/-5% of control), the entry induced by depletion of reservoirs with the ionophore undergoes a significant reduction in a solution bubbled with CO (84+/-5% of control). In agreement with the concept that CO has a direct inhibitory effect on capacitative calcium entry, a reduction to 47+/-6% of control was obtained when sarco/endoplasmic reticulum ATPase was blocked by thapsigargin. Diverse mechanisms could be responsible for the effect of CO on calcium entry. On the one hand, a decrease in the calcium release from intracellular stores or an increase in the rate of its back-sequestration could occur, being the reduction of capacitative calcium entry an indirect consequence of a diminished emptying of reservoirs. On the other hand, CO could have a direct inhibitory effect on the pathway that produces the calcium entry. The decrease in the Ca(2+) signal in the presence of CO evoked by receptor-independent emptying of reservoirs indicates that a direct effect of CO on capacitative calcium entry participates in the antiaggregatory properties of CO. The proposal that CO inhibits directly store-operated calcium influx widens the potential mechanisms by which heme oxygenase regulates cell functions.
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PMID:Carbon monoxide inhibits capacitative calcium entry in human platelets. 1530 53

We sought to identify novel genes involved in intestinal iron absorption by inducing iron deficiency in rats during postnatal development from the suckling period through adulthood. We then performed comparative gene chip analyses (RAE230A and RAE230B chips; Affymetrix) with cRNA derived from duodenal mucosa. Real-time PCR was used to confirm changes in gene expression. Genes encoding the apical iron transport-related proteins [divalent metal transporter 1 (DMT1) and duodenal cytochrome b] were strongly induced at all ages studied, whereas increases in mRNA encoding the basolateral proteins iron-regulated gene 1 and hephaestin were observed only by real-time PCR. In addition, transferrin receptor 1 and heme oxygenase 1 were induced. We also identified induction of novel genes not previously associated with intestinal iron transport. The Menkes copper ATPase (ATP7a) and metallothionein were strongly induced at all ages studied, suggesting increased copper absorption by enterocytes during iron deficiency. We also found significantly increased liver copper levels in 7- to 12-wk-old iron-deficient rats. Also upregulated at most ages examined were the sodium-dependent vitamin C transporter, tripartite motif protein 27, aquaporin 4, lipocalin-interacting membrane receptor, and the breast cancer-resistance protein (ABCG2). Some genes also showed decreased expression with iron deprivation, including several membrane transporters, metabolic enzymes, and genes involved in the oxidative stress response. We speculate that dietary iron deprivation leads to increased intestinal copper absorption via DMT1 on the brush-border membrane and the Menkes copper ATPase on the basolateral membrane. These findings may thus explain copper loading in the iron-deficient state. We also demonstrate that many other novel genes may be differentially regulated in the setting of iron deprivation.
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PMID:Identification of differentially expressed genes in response to dietary iron deprivation in rat duodenum. 1563 78

The present study was designed to examine whether aqueous extract of steamed root of Rehmannia glutinose (ARR) has an ameliorative effect on renal functional parameters in association with the expressions of aquaporin 2 (AQP 2), Na,K-ATPase, and heme oxygenase-1 (HO-1) in the ischemia-reperfusion induced acute renal failure (ARF) rats. Polyuria caused by down-regulation of renal AQP 2 in the ischemia-induced ARF rats was markedly restored by administration of ARR (200 mg/kg, p.o.) with restoring expression of AQP 2 in the kidney. The expressions of Na,K-ATPase alpha1 and beta1 subunits in the renal medullar and cortex of the ARF rats were also restored in the ARF rats by administration of ARR. On the other hand, administration of ARR lowered the renal expression of HO-1 up-regulated in rats with ischemia-induced ARF. The renal functional parameters including creatinine clearance, urinary sodium excretion, urinary osmolality, and solute-free reabsorption were also markedly restored in ischemia-ARF rats by administration of ARR. Taken together, these data indicate that RSR ameliorates renal defects in rats with ischemia-induced ARF.
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PMID:Rehmannia glutinose ameliorates renal function in the ischemia/reperfusion-induced acute renal failure rats. 1614 36

The present study was designed to examine whether Yukmijihwang-tang (YJT), which is a Korean decoction for the treatment of renal disease, has an effect on renal functional parameters in association with the expression of aquaporin 2 (AQP 2), Na,K-ATPase, heme oxygenase-1 (HO-1) in rats with ischemia/reperfusion-induced acute renal failure (ARF). Polyuria caused by down-regulation of renal AQP 2 in the ischemia/reperfusion-induced ARF rats was markedly restored by administration of YJT (100 or 200 mg/kg, p.o.) with restoring expression of AQP 2 in the kidney. The expressions of Na,K-ATPase alpha1 and beta1 subunits in the renal medulla and cortex of the ARF rats were also restored in them by the administration of YJT. Administration of YJT lowered the expression of renal HO-1, which was up-regulated in rats with ischemia/reperfusion-induced ARF. The renal functional parameters including creatinine clearance, urinary sodium excretion, urinary osmolality, and solute-free reabsorption were also markedly restored in ischemia-ARF rats by administration of YJT. Histological study also showed that renal damages in the ARF rats were abrogated by administration of YJT. Taken together, these data indicate that YJT ameliorates renal defects in rats with ischemia/reperfusion-induced ARF.
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PMID:Yukmijihwang-tang ameliorates ischemia/reperfusion-induced renal injury in rats. 1618 23

Paraquat, one of the most widely used herbicides, is highly toxic to humans and animals. There is much information regarding its toxic effects on the lungs, but less is known about its toxicity in other organs. Paraquat is thought to play pivotal roles in the pathophysiology of acute renal failure and the progression of chronic kidney disease. We investigated the effects of paraquat on gene expression in the kidneys of rats treated with paraquat using a DNA array system, and the gene up-regulation observed was confirmed by quantitative real-time RT-PCR. Rats were sacrificed at 3, 24 h after the first injection (20 mg/kg), and at 3 h after the second injection. Expression of six genes had increased significantly by 3 h after the first injection: metallothionein-1 (MT-1), phosphoenolpyruvate carboxykinase, Na/K-transporting ATPase beta1 subunit, glutamate oxaloacetic transaminase, glutathione-S-transferase, and heme oxygenase-1 (HO-1). The transcription levels of MT-1 and HO-1 showed the biggest increases, but the increases did not continue until 24 h after injection, and the second injection had less effect than the first. Up-regulation of MT-1 and HO-1 mRNA levels was confirmed at the protein level. We observed a paraquat-induced increase of these proteins at 3 h post-injection, whereas this level did not continue until 24 h, as observed in RNA levels. The MT-1 protein in kidneys had been consumed. In addition, the protein level due to the second injection did not increase to the same level as that due to the first injection. These results suggest that protection against paraquat injury is mediated by induction of expression of some genes, and suppression on the induction of MT-1 and HO-1 may explain the injury observed due to paraquat intake. This is the first report of inducible pathways of defense against paraquat-induced oxidative stress in the kidney.
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PMID:Paraquat-induced gene expression in rat kidney. 1655 45

Previous studies revealed novel genetic changes in the duodenal mucosa of iron-deprived rats during postnatal development. These observations are now extended to compare the genetic response to iron deficiency in the duodenum versus jejunum of 12-wk-old rats. cRNA samples were prepared from the duodenal and jejunal mucosa of three groups each of control and iron-deficient rats and hybridized with RAE 230A and 230B gene chips (Affymetrix). Stringent data reduction strategies were employed. Results showed that several genes were similarly induced in both gut segments, including DMT1, Dcytb, transferrin receptor 1, heme oxygenase 1, metallothionein, the Menkes copper ATPase (ATP7A), tripartitie motif protein 27, and the sodium-dependent vitamin C transporter. However, a subset of genes showed regulation in only one or the other gut segment. In duodenum only, gastrokine 1, trefoil factor 1 and claudin 2 were induced by iron-deficiency. Other genes previously identified were only regulated in the duodenum. Overall, these studies demonstrate similarities and distinct differences in the genetic response to iron deprivation in the duodenum versus jejunum and provide evidence that more distal gut segments also may play a role in increasing iron absorption in iron-deficiency anemia.
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PMID:Gene chip analyses reveal differential genetic responses to iron deficiency in rat duodenum and jejunum. 1662 62

The present study investigated the cellular mechanism underlying the degradation of heme oxygenase-1 (HO-1), an endoplasmic reticulum (ER)-anchored protein. The turnover of HO-1 induced in vascular smooth muscle cells (VSMCs) was significantly attenuated by proteasome inhibitors, suggesting the involvement of a proteasome-mediated pathway. High molecular weight ubiquitin conjugates were co-immunoprecipitated with HO-1 from VSMCs after proteasome inhibition, and HO-1 ubiquitination was confirmed in HEK293 cells overexpressing His-tagged HO-1 and HA-tagged ubiquitin. Endogenous p97, an ATPase, and Ufd1, both implicated as essential components in the ER-associated degradation pathway (ERAD), were co-eluted with His-tagged HO-1 from metal affinity resin. Knockdown of either p97 or Ufd1 in HEK293 cells using specific siRNA significantly prolonged the half-life of endogenously induced HO-1 and slowed the degradation of ubiquitinated HO-1. HO-1 ubiquitination in HEK293 cells was enhanced by zinc chloride, but suppressed with a zinc chelator (N,N,N',N'-tetrakis(2-pyridylmethyl)ethyl-enediamine), suggesting the involvement of a RING-E3 ligase in this process. Collectively, these data indicate that HO-1 protein turnover is regulated by the ubiquitin-proteasome system through the ERAD pathway.
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PMID:Ubiquitin-proteasome system mediates heme oxygenase-1 degradation through endoplasmic reticulum-associated degradation pathway. 1854 48

Given that the physiology of heme oxygenase-1 (HO-1) encompasses mitochondrial biogenesis, we tested the hypothesis that the HO-1 product, carbon monoxide (CO), activates mitochondrial biogenesis in skeletal muscle and enhances maximal oxygen uptake (Vo(2max)) in humans. In 10 healthy subjects, we biopsied the vastus lateralis and performed Vo(2max) tests followed by blinded randomization to air or CO breathing (1 h/day at 100 parts/million for 5 days), a contralateral muscle biopsy on day 5, and repeat Vo(2max) testing on day 8. Six independent subjects underwent CO breathing and two muscle biopsies without exercise testing. Molecular studies were performed by real-time RT-PCR, Western blot analysis, and immunochemistry. After Vo(2max) testing plus CO breathing, significant increases were found in mRNA levels for nuclear respiratory factor-1, peroxisome proliferator-activated receptor-gamma coactivator-1alpha, mitochondrial transcription factor-A (Tfam), and DNA polymerase gamma (Polgamma) with no change in mitochondrial DNA (mtDNA) copy number or Vo(2max). Levels of myosin heavy chain I and nuclear-encoded HO-1, superoxide dismutase-2, citrate synthase, mitofusin-1 and -2, and mitochondrial-encoded cytochrome oxidase subunit-I (COX-I) and ATPase-6 proteins increased significantly. None of these responses were reproduced by Vo(2max) testing alone, whereas CO alone increased Tfam and Polgamma mRNA, and COX-I, ATPase-6, mitofusin-2, HO-1, and superoxide dismutase protein. These findings provide evidence linking the HO/CO response involved in mitochondrial biogenesis in rodents to skeletal muscle in humans through a set of responses involving regulation of the mtDNA transcriptosome and mitochondrial fusion proteins autonomously of changes in exercise capacity.
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PMID:Carbon monoxide, skeletal muscle oxidative stress, and mitochondrial biogenesis in humans. 1946 54

For the application of microarray technology as an additional endpoint in toxicological studies, there is a need to understand associations between pathological processes and gene expression alterations. In the current study, we investigated gentamicin as a nephrotoxic model compound. Gene expression changes of the kidney in response to a dose of 80 mg/kg gentamicin were analyzed by using DNA microarray technology and alterations in gene expression were associated with results from conventional histopathological investigations and with the described pathomechanisms of gentamicin. Under the conditions of our experiment, the mRNA level of 211 genes were found to be deregulated by gentamicin. The gentamicin-induced affection of proximal convoluted tubules was associated with a strong up-regulation of mRNAs encoding for proteins which are used as nephrotoxicity markers in urine and plasma such as Kim-1, Osteopontin and TIMP1. Candidate marker genes for nephrotoxicity such as GATM were deregulated. Gentamicin-induced lysosomal phospholipidosis was indicated by deregulation of lysosomal located gene products such as ATP6V1D, a subunit of the lysosomal H+ transporting ATPase. Effects on glucose transport and metabolism were indicated by the down-regulation on SGLT-2 and glucose-6-phosphatase. Renal cell apoptosis was indicated by up-regulated genes as TP53 and BAX. The role of oxidative stress in gentamicin toxicity was reflected by deregulation of transferrin receptor and heme oxygenase. The results of the study show the potential of microarray technology to study a complex mechanism of toxicity in a single study.
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PMID:Identification of genes involved in gentamicin-induced nephrotoxicity in rats--a toxicogenomic investigation. 1966 12


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