Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P50583 (asymmetrical)
 12,197 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It is well known that arginine vasopressin (AVP) produces up to a 40-fold increase (0.1 to 4.0 microL/min.cm2) in net water flux across the amphibian urinary bladder under an osmotic gradient (mucosal side 10% hypotonic). No AVP effect is observed when the gradient is in the opposite direction (serosal hypotonic). Similar asymmetrical behavior to osmotic gradients occurs in the frog corneal epithelium. This rectification phenomenon has not been satisfactorily explained. We measured net water fluxes in bladder sacs and confirmed that AVP has no effect when the serosal bath is hypotonic. We reasoned that the 'abnormal' serosal osmolarity was inducing changes in membrane water permeability, the very parameter being measured. Thus, we studied the effect of solution osmolarity on diffusional water flow (Jdw) across the frog bladder using 3H2O. As expected, AVP doubled Jdw (in either direction from 12 to 21 microL/min.cm2) when the serosal solution was iso-osmolar regardless of mucosal osmolarity. However, in the AVP-stimulated bladders, hypo-osmolarity of the serosal solution reduced Jdw by 42%, an effect that was reversible when normal osmolarity was re-established. Amphotericin B (instead of AVP) was used to irreversibly increase the permeability to water of the apical membrane. Under these conditions, basolateral hypotonicity also reversibly decreased Jdw by 32%, suggesting the basolateral membrane as the site where permeability is reduced. SEM and TEM of the tissue shows extreme swelling when it was exposed to serosal hypotonicity with or without AVP and typical surface morphology changes following hormone stimulation. We conclude that this swelling may initiate a signaling mechanism that reduces basolateral water permeability. These findings constitute evidence of basolateral water channel permeability regulation, which can also contribute to cell volume regulation.
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PMID:Evidence of basolateral water permeability regulation in amphibian urinary bladder. 946 4

We have used freeze-fracture electron microscopy to examine the oligomeric structure and molecular asymmetry of integral plasma membrane proteins. Recombinant plasma membrane proteins were functionally expressed in Xenopus laevis oocytes, and the dimensions of their freeze-fracture particles were analyzed. To characterize the freeze-fracture particles, we compared the particle cross-sectional area of proteins with alpha-helical transmembrane domains (opsin, aquaporin 1, and a connexin) with their area obtained from existing maps calculated from two-dimensional crystals. We show that the cross-sectional area of the freeze-fracture particles corresponds to the area of the transmembrane domain of the protein, and that the protein cross-sectional area varies linearly with the number membrane-spanning helices. On average, each helix occupies 1.40 +/- 0.03 nm2. By using this information, we examined members from three classes of plasma membrane proteins: two ion channels, the cystic fibrosis transmembrane conductance regulator and connexin 50 hemi-channel; a water channel, the major intrinsic protein (the aquaporin 0); and a cotransporter, the Na+/glucose cotransporter. Our results suggest that the cystic fibrosis transmembrane conductance regulator is a dimer containing 25 +/- 2 transmembrane helices, connexin 50 is a hexamer containing 24 +/- 3 helices, the major intrinsic protein is a tetramer containing 24 +/- 3 helices, and the Na+/glucose cotransporter is an asymmetrical monomer containing 15 +/- 2 helices.
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PMID:Structural analysis of cloned plasma membrane proteins by freeze-fracture electron microscopy. 973 19

Optical coherence tomography (OCT) provides a new dimenstion in ophthalmology because it allows evaluation of the pathology in vivo, and provides information to assist the management of macular disease and glaucoma. It is necessary to differentiate the diagnosis of glaucoma from diseases of the optic nerve and of the visual pathway. This study evaluates the usefulness of OCT in detecting disorders of the optic nerve and visual pathway. In addition, the pathogenesis of glaucomatous optic neuropathy (GON), the most common optic neuropathy, was investigated by focusing on the dynamics of aquaporin. I. Evaluation of optic nerve and visual pathway disorders by optical coherence tomography. The swinging flashlight test is an easy, sensitive, objective test to detect relative afferent pupillary defects (RAPD). The number of RAPD detected by the swinging flashlight test was closely correlated with the ratio of retinal nerve fiber layer thickness (RNFLT) between the two eyes of 20 cases of unilateral optic atrophy. OCT could assess the amount of RAPD that reflected an asymmetrical functional disturbance of the optic nerves, as a structural difference. The time courses of RNFLT and ganglion cell complex (GCC) changes' were observed immediately following the time of injury in 4 cases of traumatic optic neuropathy. OCT revealed that both the RNFLT and GCC decreased rapidly from 2 weeks after the injury until 20 weeks later. The RNFLT decreased significantly in the horizontal direction in comparison to the perpendicular direction in 34 eyes from the cases of optic chiasm syndrome. This means that OCT could quantitatively detect the band atrophy of the optic disc in optic chiasm syndrome. Measuring the RNFLT showed a thinning of RNFLT in the perpendicular direction in comparison to the horizontal direction in ipsilateral eyes and thinning in the horizontal direction in comparison to the perpendicular direction in the contralateral eyes in optic tract syndrome. Measuring the GCC showed a thinning of the GCC in the temporal hemifield to the central fovea of the ipsilateral eyes, and thinning of the GCC in the nasal hemifield of the contralateral eyes. This means that OCT could detect the structural changes of hourglass atrophy in the ipsilateral eye and band atrophy in the contralateral eye at the optic disc as well as the homonymous hemianopia in the visual field. OCT was useful in evaluating the optic nerve and visual pathway disorders, but there were also some limitations. The thinning area of RNFLT measured by OPTVue and Cirrus were in entirely opposite directions in cases of optic chasm syndrome. The reason was attributed to the better performance of RTVue in measuring a thin RNFLT on the nasal side of the optic disc in comparison to Cirrus. The specific characteristics of the instruments should be considered when the results of OCT are evaluated. II. Dynamics of aquaporin in the optic nerve Aquaporin (AQP) is a membrane protein that forms a water channel to facilitate water crossing the plasma membrane. AQP-4 was originally thought to be expressed in the optic nerve, but it is expressed only in the retrobulbar medullated region of the optic nerve and the expression of AQPs in the optic disc has not been detected. This study investigated the expressions of AQPs in the optic nerve in rat, monkey and human. The results demonstrate that only AQP-9 was expressed at the unmedullated pre-lamina cribrosa and lamina cribrosa regions, and both AQP-4 and AQP-9 were expressed at the medullated retrobulbar region. Astrocytes were observed to express AQP-9, because AQP-9 immunoreactivity was identical to that of glial fibrillary acidic protein. Elevated intraocular pressure substantially reduced AQP-9 expression in the optic nerve, whereas expression of AQP-4 was not changed in rat eyes. The same phenomena were also observed in the monkey eye with ocular hypertension as well as human eye with glaucoma. AQP-9 is an aquaglyceroporin that allows solutes such as lactate rather than water to cross the cell membrane. The astrocyte-to-neuron lactate shuttle hypothesis has been proposed, in which lactate transported from astrocytes is used by neurons as an energy substrate. Reduction of AQP-9 expression in the optic nerve head under elevated intraocular pressures might be closely related to the pathogenesis of GON.
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PMID:[New insights into the study of optic nerve diseases]. 2363 Dec 54