Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The lens major intrinsic protein (MIP, AQP0) is known to function as a water and solute channel. However, MIP has also been reported to occur in close membrane contacts between lens fiber cells, indicating that it has adhesive properties in addition to its channel function. Using atomic force and cryo-electron microscopy we document that crystalline sheets reconstituted from purified ovine lens MIP mostly consisted of two layers. MIP lattices in the apposing membranes were in precise register, and determination of the membrane sidedness demonstrated that MIP molecules bound to each other via their extracellular surfaces. The surface structure of the latter was resolved to 0.61 nm and revealed two protruding domains providing a tight "tongue-and-groove" fit between apposing MIP molecules. Cryo-electron crystallography produced a projection map at 0.69 nm resolution with a mirror symmetry axis at 45 degrees to the lattice which was consistent with the double-layered nature of the reconstituted sheets. These data strongly suggest an adhesive function of MIP, and strengthen the view that MIP serves dual roles in the lens.
J Mol Biol 2000 Jul 21
PMID:Surface tongue-and-groove contours on lens MIP facilitate cell-to-cell adherence. 1089 Dec 68

Opacities in the crystalline lens of eye appear with high frequency in the general population. Dominantly inherited cataracts with differing clinical features were found in two families carrying different point mutations in the gene encoding lens water channel protein AQP0 (major intrinsic protein, MIP). Families with E134G have a uni-lamellar cataract which is stable after birth, whereas families with T138R have multi-focal opacities which increase throughout life. To establish pathophysiological relevance of cataract formation, the Xenopus laevis oocyte expression system was employed to evaluate functional defects in the mutant proteins, E134G and T138R. Both substitutions cause loss of membrane water channel activity due to impaired trafficking of the mutant proteins to the oocyte plasma membrane. Although missense mutations in AQP1 and AQP2 proteins are known to result in recessive traits in vivo and in vitro, when E134G or T138R are co-expressed with wild-type AQP0 protein, the mutant proteins exhibit dominant negative behaviour. To our knowledge, these studies represent the first in vitro demonstration of functionally defective AQP0 protein from humans with congenital cataracts. Moreover, these observations predict that less severe defects in the AQP0 protein may contribute to lens opacity in patients with common, less fulminant forms of cataracts.
Hum Mol Genet 2000 Sep 22
PMID:Functional impairment of lens aquaporin in two families with dominantly inherited cataracts. 1100 37

We have recently demonstrated that primary cultured rat pneumocytes produce macrophage inflammatory protein-2 (MIP-2) in response to lipopolysaccharide (LPS) stimulation. In this study, we found that brefeldin A, by blocking anterograde transport from the endoplasmic reticulum (ER) to the Golgi apparatus, decreased LPS-induced MIP-2 in the culture medium and increased its storage in cells. This suggests that MIP-2 is secreted via a pathway from the ER to the Golgi apparatus, a process commonly regulated by microtubules. We further found that LPS induced depolymerization of microtubules as early as 1 min after LPS stimulation, and it lasted at least for 4 h. Preventing depolymerization of microtubules with paclitaxel (Taxol; 10 nM to 10 microM) partially inhibited LPS-induced MIP-2 production, whereas the microtubule-depolymerizing agents colchicine (1-10 microM) and nocodazole (1-100 microM) increased LPS-induced MIP-2 protein production without affecting MIP-2 mRNA expression. These results suggest that in pneumocytes, LPS-induced microtubule depolymerization is involved in LPS-induced MIP-2 production and that secretion of MIP-2 from pneumocytes is via the ER-Golgi pathway.
Am J Physiol Lung Cell Mol Physiol 2000 Dec
PMID:Role of microtubules in LPS-induced macrophage inflammatory protein-2 production from rat pneumocytes. 1107 97

Acute lung injury is characterized by accumulation of neutrophils in the lungs, accompanied by the development of interstitial edema and an intense inflammatory response. To assess the role of neutrophils as early immune effectors in hemorrhage- or endotoxemia-induced lung injury, mice were made neutropenic with cyclophosphamide or anti-neutrophil antibodies. Endotoxemia- or hemorrhage-induced lung edema was significantly reduced in neutropenic animals. Activation of the transcriptional regulatory factor nuclear factor-kappaB after hemorrhage or endotoxemia was diminished in the lungs of neutropenic mice compared with nonneutropenic controls. Hemorrhage or endotoxemia was followed by increases in pulmonary mRNA and protein levels for interleukin-1beta (IL-1beta), macrophage inflammatory protein-2 (MIP-2), and tumor necrosis factor-alpha (TNF-alpha). Endotoxin-induced increases in proinflammatory cytokine expression were greater than those found after hemorrhage. The amounts of mRNA or protein for IL-1beta, MIP-2, and TNF-alpha were significantly lower after hemorrhage in the lungs of neutropenic versus nonneutropenic mice. Neutropenia was associated with significant reductions in IL-1beta and MIP-2 but not in TNF-alpha expression in the lungs after endotoxemia. These experiments show that neutrophils play a central role in initiating acute inflammatory responses and causing injury in the lungs after hemorrhage or endotoxemia.
Am J Physiol Lung Cell Mol Physiol 2000 Dec
PMID:Neutrophils as early immunologic effectors in hemorrhage- or endotoxemia-induced acute lung injury. 1107 4

We have previously demonstrated that lipopolysaccharide (LPS) induces production of macrophage inflammatory protein-2 (MIP-2), a C-X-C chemokine for neutrophil recruitment and activation, in primary cultured rat lung alveolar epithelial cells. We have also demonstrated that LPS depolymerizes microfilaments in rat alveolar epithelial cells. To determine whether the polymerization status of microfilaments affects LPS-induced MIP-2 production, we treated rat alveolar epithelial cells with cytochalasin D (CytoD), a microfilament-disrupting agent, before and during LPS stimulation. A lower concentration (0.1 microM) of CytoD inhibited LPS-induced MIP-2 production without affecting microfilament polymerization. In contrast, LPS-induced MIP-2 production was enhanced by a higher concentration (10 microM) of CytoD, which disrupted the filamentous structure of actin. Jasplakinolide (1 nM to 1 microM), a polymerizing agent for microfilaments, decreased LPS-induced MIP-2 secretion. Jasplakinolide (1 microM) also blocked LPS-induced depolymerization of microfilaments. These results suggest that, in alveolar epithelial cells, LPS-induced MIP-2 production is at least partially regulated by microfilament depolymerization.
Am J Physiol Lung Cell Mol Physiol 2001 Apr
PMID:Role of LPS-induced microfilament depolymerization in MIP-2 production from rat pneumocytes. 1123 18

In crucifers, the ability of the stigma to differentially modulate hydration of pollen grains, depending on whether the pollen is recognized to be compatible or incompatible, represents a crucial stage in pollination. Our recent analysis of the mod mutation of Brassica, which results in a breakdown of the self-incompatibility response, led to the isolation of a gene linked to the MOD locus which is expressed at low levels in mod mutants. The gene is predicted to encode a plasma membrane-localized aquaporin-like protein and has been designated MIP-MOD. We utilized reporter gene analysis to demonstrate that the MIP-MOD promoter is active in Brassica papillar cells as well as in some vegetative tissues. The encoded protein is also likely to be plasma membrane-localized based on the observation that all plasma membrane-intrinsic aquaporin-like proteins in Brassica leaves are enriched in plasma membrane fractions. The MIP-MOD protein results in a low but measurable enhancement in osmotic water permeability of Xenopus oocytes and hence represents a functional aquaporin. The results are consistent with the notion that MIP-MOD is involved in the regulation of water transport across the stigma epidermal cell membrane.
Plant Mol Biol 2001 Jan
PMID:The brassica MIP-MOD gene encodes a functional water channel that is expressed in the stigma epidermis. 1124 6

The MIP-MOD (for MOD-locus associated Major Intrinsic Protein) gene encodes an aquaporin-like product, and has been reported to be a candidate for the MOD gene which is required for the self-incompatibility response in Brassica rapa. In an antisense suppression experiment designed to investigate the role of MIP-MOD, we found that levels of MIP-MOD mRNA in the stigmas of fourteen antisense transgenics, as well as in the self-incompatible cultivar Osome (Osm), were much lower than in the stigmas of the self-incompatible S8 homozygous (S8) strain. Therefore, we analyzed the molecular structure of the MIP-MOD gene in three B. rapa strains: S8, Osm, and the self-compatible var. Yellow Sarson (YS). Nucleotide sequence analysis of the MIP-MOD genes isolated from the three strains revealed that all three encode the same amino acid sequence and that YS and Osm contain the same MIP-MOD allele, designated MIP-MOD(YS). Analysis of other self-incompatible B. rapa strains that are homozygous for the MIP-MOD(YS) allele indicated that high levels of MIP-MOD transcripts are not essential for the self-incompatibility response. Furthermore, a MOD mutant generated by gamma-irradiation was found to contain a wild-type MIP-MOD gene that is expressed at normal levels. These data suggest that MIP-MOD is not MOD itself. We suggest that this gene should be renamed MLM (for MIP gene linked to MOD).
Mol Genet Genomics 2001 May
PMID:Molecular genetic analysis of the candidate gene for MOD, a locus required for self-incompatibility in Brassica rapa. 1140 35

With the aim of identifying cells and tissues with high expression of aquaporins (water channels) or homologous genes in Norway spruce (Picea abies), we report the expression patterns of such transcripts in seedlings, in roots of various ages, and in needles. In situ hybridization experiments with a conserved area of a tonoplast intrinsic protein (TIP) gene from P. abies gave high expression signals in differentiating vascular tissues and in the columella cells of the seedling root cap. High-staining signals were also seen in guard cells and in the bundle sheath cells of needles. Moreover, a slightly increased staining signal was seen in cells forming lateral roots as well as in adventitious roots formed from hypocotyl cuttings. By using PCR-based procedures we also identified a full-length aquaporin-like cDNA (mipr) from roots of two-week old seedlings. Sequence homology analysis of the gene suggests that it belongs to the TIP subgroup within the large MIP (major intrinsic protein) family. A phylogenetic analysis of the plant MIP family, including both plasmamembrane (PIP) and tonoplast intrinsic protein (TIP) from Picea, suggests that MIP subgroups evolved already 330 million years ago, as this is the dating of conifer and angiosperm divergence.
Plant Mol Biol 2001 Jun
PMID:Expression pattern of transcripts encoding water channel-like proteins in Norway spruce (Picea abies). 1148 76

Coxsackievirus B3 (CVB3)-induced myocarditis in NMRI mice represents a model for studying the pathogenesis of this chronic heart disease. Previously, we reported on specific cytokine patterns during the acute stage of myocarditis since cytokines are thought to play the important role in this cardiomyopathy. In this study, the expression of various cytokine mRNAs and CVB3-RNA kinetics was examined with particular emphasis on the late phase of myocarditis, by using reverse transcriptase-polymerase chain reaction (RT-PCR), in situ hybridization (ISH) and immunohistochemistry (IHC). In addition, replicating and persisting CVB3-RNAs were semiquantified by PCR-ELISA. Distinct histopathological changes responsible for ongoing heart disease were found and characterized by increased fibrosis, persistent cellular infiltration and degenerated necrotic myocytes. One of the most important findings of this study was that the mRNA-expression of TNF- alpha, IL-1 alpha, interferon- gamma, IL-10, IL-18, macrophage inflammatory protein-1 alpha (MIP-1 alpha), transforming growth factor- beta (TGF- beta) and inducible nitric oxide synthase (iNOS) persisted as long as 98 days after the virus infection. The induction of IL-10 as well as IFN- gamma mRNAs was also verified by ISH and IHC at days 28 and 98 p.i. The clearly apparent persistence of the viral genomes in the myocardium of infected mice was confirmed by seminested PCR, ISH, and PCR-enzyme linked immunoabsorbent assay (ELISA), showing the highest amount of viral RNA in myocardial cells at day 7 after infection. These data indicate that the persistence of viral RNA is associated with persistently high levels of cytokine mRNAs which, when translated, could severely contribute to pathological changes and injury of connective tissue in the chronic stage of myocarditis.
J Mol Cell Cardiol 2001 Sep
PMID:Persistent expression of cytokines in the chronic stage of CVB3-induced myocarditis in NMRI mice. 1154 41

Molecular analysis of CCR5, the cardinal coreceptor for HIV-1 infection, has implicated the N-terminal extracellular domain (N-ter) and regions vicinal to the second extracellular loop (ECL2) in this activity. It was shown that residues in the N-ter are necessary for binding of the physiologic ligands, RANTES (CCL5) and MIP-1 alpha (CCL3). vMIP-II, encoded by the Kaposi's sarcoma-associated herpesvirus, is a high affinity CCR5 antagonist, but lacks efficacy as a coreceptor inhibitor. Therefore, we compared the mechanism for engagement by vMIP-II of CCR5 to its interaction with physiologic ligands. RANTES, MIP-1 alpha, and vMIP-II bound CCR5 at high affinity, but demonstrated partial cross-competition. Characterization of 15 CCR5 alanine scanning mutants of charged extracellular amino acids revealed that alteration of acidic residues in the distal N-ter abrogated binding of RANTES, MIP-1 alpha, and vMIP-II. Whereas mutation of residues in ECL2 of CCR5 dramatically reduced the binding of RANTES and MIP-1 alpha and their ability to induce signaling, interaction with vMIP-II was not altered by any mutation in the exoloops of the receptor. Paradoxically, monoclonal antibodies to N-ter epitopes did not block chemokine binding, but those mapped to ECL2 were effective inhibitors. A CCR5 chimera with the distal N-ter residues of CXCR2 bound MIP-1 alpha and vMIP-II with an affinity similar to that of the wild-type receptor. Engagement of CCR5 by vMIP-II, but not RANTES or MIP-1 alpha blocked the binding of monoclonal antibodies to the receptor, providing additional evidence for a distinct mechanism for viral chemokine binding. Analysis of the coreceptor activity of randomly generated mouse-human CCR5 chimeras implicated residues in ECL2 between H173 and V197 in this function. RANTES, but not vMIP-II blocked CCR5 M-tropic coreceptor activity in the fusion assay. The insensitivity of vMIP-II binding to mutations in ECL2 provides a potential rationale to its inefficiency as an antagonist of CCR5 coreceptor activity. These findings suggest that the molecular anatomy of CCR5 binding plays a critical role in antagonism of coreceptor activity.
J Mol Biol 2001 Nov 09
PMID:Molecular anatomy of CCR5 engagement by physiologic and viral chemokines and HIV-1 envelope glycoproteins: differences in primary structural requirements for RANTES, MIP-1 alpha, and vMIP-II Binding. 1170 73


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