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)

Increased urine flow is often a feature of mild to moderate acute renal failure. This study examines the possible role of dysregulation of collecting duct aquaporins as a factor in this increase. In rats, the left renal pedicle was clamped for 45 min followed by contralateral nephrectomy. Control rats were identical except that the renal pedicle was not clamped. Rats were sacrificed and the kidneys were homogenized at various time points after release of the clamp for semiquantitative immunoblotting of collecting duct aquaporins, as well as the thick ascending limb Na-K-2Cl cotransporter and the proximal tubule water channel, aquaporin-1. Urinary flow rate was significantly increased 18 h after the ischemic insult and remained increased through 72 h. Whole kidney aquaporin-2 protein abundance was 45% of controls at 18 h, 55% of controls at 36 h, and returned to normal 72 h after ischemia. Whole kidney aquaporin-3 protein abundance was 37% of controls at 18 h, 13% of controls at 36 h, and 45% of controls at 72 h. The decline in aquaporin-2 and -3 was confirmed by immunocytochemistry. Abundance of the thick ascending limb Na-K-2Cl cotransporter protein was not significantly decreased. Aquaporin-1 protein abundance was not significantly decreased at 18 h after the ischemic insult, but was significantly reduced after 36 h. Thus, the post-ischemic state is associated with decreased levels of the collecting duct aquaporins, coinciding with an increase in water excretion. It is concluded that decreased aquaporin protein abundance in collecting duct cells is a contributing factor in the increased urine flow seen in moderate post-ischernic acute renal failure.
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PMID:Decreased abundance of collecting duct aquaporins in post-ischemic renal failure in rats. 1044 33

Exocytosis of intravesicular material should help a cell meet a relative extracellular hyposmotic challenge by expanding the plasmalemma through fusion with vesicular membrane. Cell swelling evokes an immediate secretory burst of hormones stored in secretory vesicles with dynamics indistinguishable from those induced by specific secretagogues. Hormone secretion induced by cell swelling is not associated with a rise in cAMP, IP(3), or prostaglandins, and it is not depressed by inhibition of stretch mechano-receptors or aquaporin channels. In contrast to most types of regulated secretion, that induced by cell swelling in normal cells does not require a rise in intracellular Ca(2+) through opening L-type Ca(2+) channels. However, such Ca(2+) influx is essential for cell-swelling induced secretion in tumor-derived pituitary cells. Cell swelling induces universal secretion of exocytotic material. The response of cells specialized in osmoregulation is, however, different. Possible physiological significance: Consistent stimulation of secretion occurs with a 4% hyposmolar challenge. It is likely that fluctuations in osmotic pressure with resultant cell volume changes have a significant regulatory role in hormone secretion. Released hormones could also play an important role in the pathophysiology of ischemia. Exocytosis itself does not have an essential role in volume regulation.
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PMID:Regulation of hormone secretion by acute cell volume changes: Ca(2+)-independent hormone secretion. 1112 21

Aquaporin-9 (AQP9) is a new member of the aquaporin family of water-selective channels mainly expressed in liver and testis, presenting the characteristic of also being permeable to various solutes, particularly lactate. Recent data have shown the presence of AQP9 on tanycytes in the rat brain. In the current study, the authors show the expression of AQP9 in astrocytes in the mouse brain and changes in its expression after cerebral ischemia. Indeed, in control mouse, the AQP9 immunolabeling is present on astrocytic processes bordering the subarachnoid space and ventricles. The labeling also is observed on astrocytes in the white matter, hippocampus, hypothalamus, and lateral septum. After focal transient ischemia, an increase of the immunolabeling is detected on astrocytes in periinfarct areas. This AQP9 distribution study in mouse brain suggests a role of AQP9 in water homeostasis in the central nervous system. Furthermore, the overexpression of AQP9 on astrocytes surrounding an ischemic lesion suggests that AQP9 may also play a role in the regulation of postischemia edema and, in view of its permeability to monocarboxylates, in the clearance of lactate from the ischemic focus.
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PMID:Astrocyte-specific expression of aquaporin-9 in mouse brain is increased after transient focal cerebral ischemia. 1133 57

The aim of the present experimental research was to study brain oxygenation parameters in relation to tissue water movement and brain cortex oedema caused by focal brain ischemia. It has been demonstrated that local osmotic dehydration of the parietal brain cortex, mercury compounds (aquaporin inhibitors) and brain cortex oedema resulting from focal brain ischemia all influence extra-capillary oxygen transport lowering tissue respiration rates and oxygen transfer coefficients. The changes of brain oxygenation parameters in case of cortex ischemic oedema are reflected in the gas composition (oxygen and carbon dioxide partial pressure) of the blood in v. jugularis. A short course of hyperbaric treatment results in normalization of water content in the brain. The results are interpreted in terms of the functioning of tissue microcirculation that might participate, at the extra-capillary level, in brain oxygenation.
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PMID:Experimental study on brain oxygenation in relation to tissue water redistribution and brain oedema. 1145 25

Water movement between cells and interstitium in spinal cord and brain occurs during neural signal transduction and in response to injuries such as ischemia and blunt trauma. At least two aquaporin-type water channels are expressed in spinal cord: AQP1 in afferent sensory nerve fibers in the superficial layers of the dorsal horn, and AQP4 in glial cells throughout gray matter. An imaging method was developed to map thickness changes in viable spinal cord and brain slices cut by a vibratome, and applied to measure osmotically induced water transport in spinal cord slices from wildtype and aquaporin knockout mice. Spinal cord slices (300 microm thickness) were mounted in a perfusion chamber with < 2 s exchange time, and transmitted light (565 nm) was imaged by a CCD camera. Changes in slice thickness were mapped from the amount of light passing through a thin ( approximately 100 microm) layer of perfusate bathing the slice, in which hemoglobin (6 mg/ml) was added to the perfusate as an inert absorbing chromophore. In response to osmotic challenges imposed by changing perfusate osmolality by 100 mOsm, transmitted light intensity changed reversibly with approximately mono-exponential kinetics whose initial rate depended upon position in the slice. In the superficial dorsal horn where AQP1 is strongly expressed, the rate of osmotic swelling was 7.0 +/- 1.3 microm/s in wildtype mice and 2.0 +/- 0.2 microm/s in AQP1 null mice; osmotic swelling was slower in deeper lamina of dorsal horn, and was decreased in AQP4 but not AQP1 null mice. These results establish a simple imaging method to map changes in water content of spinal cord slices, and provide evidence that aquaporins facilitate osmotic water transport in functionally relevant areas of the spinal cord.
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PMID:Optical measurement of swelling and water transport in spinal cord slices from aquaporin null mice. 1174 25

Water homeostasis in the brain is of central physiologic and clinical importance. Neuronal activity and ion water homeostasis are inextricably coupled. For example, the clearance of K+ from areas of high neuronal activity is associated with a concomitant water flux. Furthermore, cerebral edema, a final common pathway of numerous neurologic diseases, including stroke, may rapidly become life threatening because of the rigid encasement of the brain. A water channel family, the aquaporins, facilitates water flux through the plasma membrane of many cell types. In rodent brain, several recent studies have demonstrated the presence of different types of aquaporins. Aquaporin 1 (AQP1) was detected on epithelial cells in the choroid plexus whereas AQP4, AQP5 and AQP9 were localized on astrocytes and ependymal cells. In rodent brain, AQP4 is present on astrocytic end-feet in contact with brain vessels, and AQP9 is found on astrocytic processes and cell bodies. In basal physiologic conditions, AQP4 and AQP9 appear to be implicated in brain homeostasis and in central plasma osmolarity regulation. Aquaporin 4 may also play a role in pathophysiologic conditions, as shown by the reduced edema formation observed after water intoxication and focal cerebral ischemia in AQP4-knockout mice. Furthermore, pathophysiologic conditions may modulate AQP4 and AQP9 expression. For example, AQP4 and AQP9 were shown to be upregulated after ischemia or after traumatic injuries. Taken together, these recent reports suggest that water homeostasis in the brain is maintained by regulatory processes that, by control of aquaporin expression and distribution, induce and organize water movements. Facilitation of these movements may contribute to the development of edema formation after acute cerebral insults such as ischemia or traumatic injury.
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PMID:Aquaporins in brain: distribution, physiology, and pathophysiology. 1191 8

The Wnt-beta-catenin pathway plays key roles in embryogenesis. Wnt-4 is known to be expressed in the mesonephric duct in embryonic development. It is tempting to speculate that the Wnt-4-beta-catenin pathway contributes to the recovery from acute renal failure (ARF). This study used an in vivo model of ARF rats to clarify the significance of the Wnt-4-beta-catenin pathway in ARF. ARF was induced by clamping the rat left renal artery for 1 h. At 3, 6, 12, 24, 48, and 72 h after reperfusion, whole kidney homogenate and total RNA were extracted for examination by Western blot analysis and real-time RT-PCR. Wnt-4 mRNA and protein expression were strongly increased at 3 to 12 h and 6 to 24 h after ischemia, respectively. In immunohistologic examination, Wnt-4 was expressed in the proximal tubules and co-expressed with aquaporin-1, GM130, and PCNA. Cyclin D1 and cyclin A were expressed at 24 to 48 h after reperfusion. In addition, the overexpression of Wnt-4 and beta-catenin promoted the cell cycle and increased the promoter activity and protein expression of cyclin D1 in LLC-PK1 cells. Taken together, these data suggest that the Wnt-4-beta-catenin pathway plays a key role in the cell cycle progression of renal tubules in ARF. The Wnt-4-beta-catenin pathway may regulate the transcription of cyclin D1 and control the regeneration of renal tubules in ARF.
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PMID:Expression and function of the developmental gene Wnt-4 during experimental acute renal failure in rats. 1270 92

Recent studies indicate a key role of aquaporin (AQP) 4 in astrocyte swelling and brain edema and suggest that AQP4 inhibition may be a new therapeutic way for reducing cerebral water accumulation. To understand the physiological role of AQP4-mediated astroglial swelling, we used 21-nucleotide small interfering RNA duplexes (siRNA) to specifically suppress AQP4 expression in astrocyte primary cultures. Semiquantitative RT-PCR experiments and Western blot analysis showed that AQP4 silencing determined a progressive and parallel reduction in AQP4 mRNA and protein. AQP4 gene suppression determined the appearance of a new morphological cell phenotype associated with a strong reduction in cell growth. Water transport measurements showed that the rate of shrinkage of AQP4 knockdown astrocytes was one-half of that of controls. Finally, cDNA microarray analysis revealed that the gene expression pattern perturbed by AQP4 gene silencing concerned ischemia-related genes, such as GLUT1 and hexokinase. Taken together, these results indicate that 1) AQP4 seems to be the major factor responsible for the fast water transport of cultured astrocytes; 2) as in skeletal muscle, AQP4 is a protein involved in cell plasticity; 3) AQP4 alteration may be a primary factor in ischemia-induced cerebral edema; and 4) RNA interference could be a new potent tool for studying AQP pathophysiology in those organs and tissues where they are expressed.
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PMID:Inhibition of aquaporin-4 expression in astrocytes by RNAi determines alteration in cell morphology, growth, and water transport and induces changes in ischemia-related genes. 1282 87

Aquaporin 9 (AQP9) is a member of the aquaporin channel family involved in water flux through plasma membranes and exhibits the distinct feature of being also permeable to monocarboxylates, such as lactate, and various solutes, including glycerol, carbamides, purines, pyrimidines, and urea. AQP9 is constitutively expressed at high levels in the liver. In the brain under physiological conditions, AQP9 was first observed in tanycytes, and then in astrocytes. Only recently, its expression was also shown in neurons. Neurons expressing AQP9 are catecholaminergic and glucose sensitive. The expression of neuronal AQP9 can be negatively regulated by insulin and in diabetic animals an increase in AQP9 expression is observed in the catecholaminergic nuclei of the hindbrain, similar to the regulation of AQP9 by insulin in the liver. Furthermore, after transient brain ischemia, AQP9 expression is increased in astrocytes and its regulation may implicate the MAP-kinase pathways stimulated in such pathological conditions. Despite these new data, the exact role of AQP9 in the brain is still unclear. However, we may hypothesize that AQP9 is implicated in brain energy metabolism, as a neutral solute channel. AQP9 could facilitate the diffusion of lactate from the astrocyte to the neuron. In glucose sensitive neurons, diffusion of lactate and glycerol could stimulate these neurons in a similar manner to glucose and could regulate the energy balance. In pathological conditions, induction of AQP9 in astrocytes could participate in the clearance of excess lactate in the extracellular space. These hypotheses concerning the function of brain AQP9 are still speculative and open new areas of investigation.
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PMID:Distribution and possible roles of aquaporin 9 in the brain. 1556 12

The aquaporin-7 (AQP7) water channel is known as a member of the aquaglyceroporins, which facilitate the transport of glycerol as well as water. Although AQP7 is abundantly expressed on the apical membrane of the proximal straight tubules in the kidney, the physiological role of AQP7 is still unknown. To investigate this, we generated AQP7 knockout mice. The water permeability of the proximal tubule brush-border membrane measured by the stopped-flow method was slightly but significantly reduced in the AQP7 knockout mice compared with that of wild-type mice (AQP7, 18.0 +/- 0.4 x 10(-3) cm/s vs. wild-type, 20.0 +/- 0.3 x 10(-3) cm/s). Although AQP7 solo-knockout mice did not exhibit a urinary concentrating defect, AQP1/AQP7 double-knockout mice had a reduction in urinary concentrating ability compared with AQP1 solo-knockout mice, suggesting that the amount of water reabsorbed through AQP7 in the proximal straight tubules is physiologically substantial. On the other hand, AQP7 knockout mice showed marked glyceroluria (AQP7, 1.7 +/- 0.34 mg/ml vs. wild-type, 0.005 +/- 0.002 mg/ml). This identified a novel glycerol reabsorption pathway in the proximal straight tubules. In two mouse models of proximal straight tubule injury, the cisplatin-induced acute renal failure (ARF) model and the ischemic ARF model, an increase in urine glycerol was observed (pretreatment, 0.007 +/- 0.005 mg/ml; cisplatin, 0.063 +/- 0.043 mg/ml; ischemia, 0.076 +/- 0.02 mg/ml), suggesting that urine glycerol could be used as a new biomarker for detecting proximal straight tubule injury.
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PMID:Defective water and glycerol transport in the proximal tubules of AQP7 knockout mice. 1627 46


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