bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mechanisms and functional aspects of intestinal calcium absorption
Authors: Bronner Felix 
Published: October 2003

AbstractCalcium absorption, in terms of mechanisms and function, is well adapted to meet the calcium needs of mammals. When calcium levels in the food are low, the active, mediated transcellular calcium transport assumes primary importance. This process is vitamin D‐dependent, largely localized in the duodenum, and involves three steps: entry across the brush border, mediated by a molecular structure, CaT1, with two components; a facilitated transport that saturates at low luminal calcium concentration; and a channel component through which most calcium enters the cell at the higher luminal concentrations. Intracellular diffusion is assured by a small, cytosolic calcium binding molecule, calbindinD9k, which carries more than 90% of the calcium that traverses the duodenal cell, thus also serving as a buffer. Extrusion is by the CaATPase and is not a limiting step. Calcium entry is reduced by more than 90% in the absence of vitamin D, with biosynthesis of calbindinD9k totally vitamin D‐dependent. Active transport is upregulated on low calcium intake and downregulated at high calcium intake, when paracellular calcium transport through the tight junctions of the intestine becomes the dominant process. The amount of calcium absorbed paracellularly is a function of the calcium gradient between lumen and plasma and of the time the chyme spends at a given intestinal site. The coexistence of mediated and nonmediated transport processes assures the organism of an adequate calcium supply, yet prevents excessive calcium absorption. J. Exp. Zool. 300A:47–52, 2003. © 2003 Wiley‐Liss, Inc.
Channels, pumps, and exchangers in the gill and kidney of freshwater fishes: Their role in ionic and acid‐base regulation
Authors: PERRY S.F. , Shahsavarani A. , Georgalis T. , Bayaa M. , Furimsky M. , Thomas S.L.Y. 
Published: October 2003

AbstractIn freshwater fishes, the gill and kidney are intricately involved in ionic and acid‐base regulation owing to the presence of numerous ion channels, pumps, or exchangers. This review summarizes recent developments in branchial and renal ion transport physiology and presents several models that integrate epithelial ion and acid‐base movements in freshwater fishes. At the gill, three cell types are potentially involved in ionic uptake: pavement cells, mitochondria‐rich (MR) PNA+ cells, and MR PNA− cells. The transfer of acidic or basic equivalents between the fish and its environment is accomplished largely by the gill and is appropriately regulated to correct acid‐base imbalances. The kidney, while less important than the gill in overall acid or base excretion, has an essential role in regulating systemic acid‐base balance by controlling HCO3− reabsorption from the filtrate. J. Exp. Zool. 300A:53–62, 2003. © 2003 Wiley‐Liss, Inc.
CFTR: What's it like inside the pore?
Authors: Liu Xuehong , Smith Stephen S. , Dawson David C. 
Published: October 2003

AbstractThe Cystic Fibrosis Conductance Regulator (CFTR) functions as a cAMP‐activated, anion‐selective channel, but the structural basis for anion permeation is not well understood. Here we summarize recent studies aimed at understanding how anions move through the CFTR channel, and the nature of the environment anions experience inside the pore. From these studies it is apparent that anion permeability selectivity and anion binding selectivity of the pore are consistent with a model based on a “dielectric tunnel.” The selectivity pattern for halides and pseudohalides can be predicted if it is assumed that permeant anions partition between bulk water and a polarizable space that is characterized by an effective dielectric constant of about 19. Covalent labeling of engineered cysteines and pH titration of engineered cysteines and histidines lead to the conclusion that the CFTR anion conduction path includes a positively charged outer vestibule. A residue in transmembrane segment 6 (TM6) (R334) appears to reside in the outer vestibule of the CFTR pore where it creates a positive electrostatic potential that enhances anion conduction. J. Exp. Zool. 300A:69–75, 2003. © 2003 Wiley‐Liss, Inc.
Voltage‐Gated ion currents of schwann cells in cell culture models of human neurofibromatosis
Authors: Fieber Lynne A. 
Published: October 2003

AbstractK+ (K) channels play a role in the proliferation of many cell types in normal cells and certain disease states. Several laboratories have studied K currents in cultured Schwann cells from models of the human diseases, neurofibromatosis type 1 (NF1) and neurofibromatosis type 2 (NF2). These diseases are characterized by the growth of Schwann cell tumors. In all cell culture NF models the K current properties differ in tumor‐derived and normal Schwann cells. Depending on the model however, the type of K channel abnormality differs. K channels appear to play a role in the proliferation of Schwann cell cultures of these disease models, because a link has been established between K current blockade and the inhibition of Schwann cell proliferation in NF1 and NF2. Differences in the proliferation response of normal Schwann cells to K channel blockers suggest that in vitro regulation of proliferation in neoplastic and normal Schwann cells is complex. J. Exp. Zool. 300A:76–83, 2003. © 2003. Wiley‐Liss, Inc.
Confocal imaging of xenobiotic transport across the blood‐brain barrier
Authors: Miller David S. 
Published: October 2003

AbstractThe brain capillary endothelium is a formidable barrier to entry of foreign chemicals into the central nervous system (CNS). For the most part it poorly distinguishes between therapeutics and neurotoxins and thus the blood‐brain barrier both protects the brain from toxic chemicals and limits our ability to treat a variety of CNS disorders. Two elements underlie the barrier function of the brain capillary endothelium: 1) a physical barrier comprised of tight junctions, which form an effective seal to intercellular diffusion, and the cells themselves, which exhibit a low rate of endocytosis, and 2) a metabolic/active barrier, comprised of specific membrane transporters expressed by the endothelial cells. We have recently developed an experimental system based on confocal microscopy to study mechanisms of transport in freshly isolated brain capillaries. Here I review studies demonstrating a major role for the ATP‐driven, xenobiotic export pump, p‐glycoprotein, in barrier function and recent experiments showing that transient inhibition of pump function can have substantial benefit for chemotherapy in an animal model of brain cancer. J. Exp. Zool. 300A:84–90, 2003. © 2003 Wiley‐Liss, Inc.
Identity and function of γ‐secretase
Authors: Kimberly W. Taylor , Wolfe Michael S. 
Published: October 2003

Abstractγ‐Secretase catalyzes intramembrane proteolysis of various type I membrane proteins, including the amyloid‐β precursor protein and the Notch receptor. Despite its importance in the pathogenesis of Alzheimer's disease and to normal development, this protease has eluded identification until only very recently. Four membrane proteins are now known to be members of the protease complex: presenilin, nicastrin, aph‐1, and pen‐2. Recent findings suggest that these four proteins are sufficient to reconstitute the active γ‐secretase complex and that together they mediate the cell surface signaling of a variety of receptors via intramembrane proteolysis. © 2003 Wiley‐Liss, Inc.
Proteolytic processing of the Alzheimer's disease amyloid precursor protein in brain and platelets
Authors: Evin Geneviève , Zhu Aiqin , Holsinger R.M. Damian , Masters Colin L. , Li Qiao‐Xin 
Published: October 2003

AbstractProteolytic processing of the amyloid precursor protein by β ‐and γ‐secretases results in the production of Alzheimer's disease (AD) Aβ amyloid peptides. Modulation of secretase activity is being investigated as a potential therapeutic approach. Recent studies with human brain have revealed that the β‐secretase protein, BACE, is increased in cortex of AD patients. Analysis of βCTF (or C99), the amyloid precursor protein (APP) product of BACE cleavage that is the direct precursor to Aβ, shows it is also elevated in AD, underlying the importance of β‐secretase cleavage in AD pathogenesis. The C‐terminal product of γ‐secretase cleavage of APP, ϵCTF (or AICD), is enriched in human brain cortical nuclear fractions, a subcellular distribution appropriate for a putative involvement of APP cytosolic domain in signal transduction. Analysis of AD cortex samples, particularly that of a carrier of a familial APP mutation, suggests that processing of APP transmembrane domain generates an alternative CTF product. All these particularities observed in the AD brain demonstrate that APP processing is altered in AD. The transgenic mouse model Tg2576 seems to be a promising laboratory tool to test potential modulators of Aβ formation. Indeed, C‐terminal products of α‐, β‐, and γ‐secretase cleavage are readily detectable in the brain of these transgenic mice. Finally, the finding of the same secretase products in platelets and neurons make platelets a potentially useful and easily accessible clinical tool to monitor effects of novel therapies based on inhibition of β‐ or γ‐secretase. © 2003 Wiley‐Liss, Inc.
Changes in spinal GDNF, BDNF, and NT‐3 expression after transient spinal cord ischemia in the rat
Authors: Tokumine Joho , Kakinohana Osamu , Cizkova Dasa , Smith Doug W. , Marsala Martin 
Published: October 2003

AbstractPrevious studies have demonstrated that the expression of several growth factors including glial cell‐derived neurotrophic factor (GDNF), brain‐derived growth factor (BDNF), and neurotrophin‐3 (NT‐3) play an important role in defining neuronal survival after brain ischemia. In the present study, using a well‐defined model of transient spinal ischemia in rat, we characterized the changes in spinal GDNF, BDNF, and NT‐3 expression as defined by enzyme‐linked immunosorbent assay (ELISA) and immunofluorescence coupled with deconvolution microscopy. In control animals, baseline levels of GDNF, BDNF, and NT‐3 (74 ± 22, 3,600 ± 270, 593 ± 176 pg/g tissue, respectively) were measured. In the ischemic group, 6 min of spinal ischemia resulted in a biphasic response with increases in tissue GDNF and BDNF concentrations at the 2‐hr and 72‐hr points after ischemia. No significant differences in NT‐3 concentration were detected. Deconvolution analysis revealed that the initial increase in tissue GDNF concentration corresponded to a neuronal upregulation whereas the late peak seen at 72 hr corresponded with increased astrocyte‐derived GDNF synthesis. Increased expression of BDNF was seen in neurons, astrocytes, and oligodendrocytes. These data suggest that the early increase in neuronal GDNF/BDNF expression likely modulates neuronal resistance/recovery during the initial period of postischemic reflow. Increased astrocyte‐derived BDNF/GDNF expression corresponds with transient activation of astrocytes and may play an active role in neuronal plasticity after non‐injurious intervals of spinal ischemia. © 2003 Wiley‐Liss, Inc.
Plastic changes of calcitonin gene‐related peptide in morphine tolerance: Behavioral and immunohistochemical study in rats
Authors: Zhou Xiang , Li Jin‐Ju , Yu Long‐Chuan 
Published: October 2003

AbstractThe present study was undertaken to investigate the plasticity of calcitonin gene‐related peptide (CGRP) in antinociception after morphine tolerance in rats. The hindpaw withdrawal latencies (HWLs) to both thermal and mechanical stimulation increased significantly after intracerebroventricular injection of 2.5 nmol of CGRP in opioid‐naive rats, indicating that CGRP produces an antinociceptive effect in the brain. Furthermore, there was an antinociceptive effect after intracerebroventricular injection of 2.5 nmol of CGRP in morphine‐tolerant rats. Interestingly, the antinociceptive effect induced by intracerebroventricular injection of CGRP was lower in morphine‐tolerant rats than that in opioid‐naive rats at the same dose. At the same time, there was downregulation of CGRP‐like immunoreactivity in both lateral septal nucleus and central nucleus of amygdala tested by immunohistochemical methods, whereas no significant changes were observed in arcuate nucleus of hypothalamus and periaqueductal gray after morphine treatment in rats. The present study demonstrates plastic changes in both CGRP‐induced antinociception and CGRP‐like immunoreactivity in rat brain after morphine tolerance, suggesting that CGRP may play an important role in morphine tolerance. © 2003 Wiley‐Liss, Inc.
Phosphoinositide 3‐kinase promotes adult subventricular neuroblast migration after stroke
Authors: Katakowski Mark , Zhang Zheng Gang , Chen Jieli , Zhang Ruilan , Wang Ying , Jiang Hao , Zhang Lijie , Robin Adam , Li Yi , Chopp Michael 
Published: October 2003

AbstractRodent adult subventricular zone (SVZ)‐derived progenitor cells abandon the rostral migratory stream (RMS)/olfactory complex postmiddle cerebral artery occlusion (MCAo) and migrate into compromised tissue, possibly playing a role in brain recovery. Using SVZ tissue explants from the adult rat, we investigated the role of the phosphoinositide 3‐kinase (PI3K) signal transduction pathway in the migration of SVZ cells. Stroke significantly (P < .01) increased migratory speed (198 ± 39 μm/day) of neuroblasts out of the SVZ explants compared with the speed (99 ± 20 μm/day) in the normal SVZ (nSVZ) explants within the first 3 days of incubation. Three‐dimensional laser scanning confocal microscopy revealed formation of neuroblast encompassing chain‐like astrocyte structures extruding from both normal and stroke explants. Western blots showed that stroke SVZ (sSVZ) explants increased Akt phosphorylation. Treatment of sSVZ explants with the selective PI3K inhibitor LY294002 significantly (P < .01) attenuated neuroblast migration and Akt phosphorylation, whereas treatment with LY294002 did not affect the number of bromodeoxyuridine (BrdU)‐ and caspase‐3‐immunoreactive cells, indicating that stroke‐enhanced neuroblast migration is independent of cell proliferation and survival. PI3K catalyzes phosphatidylinositol‐3,4,5‐triphosphate (PIP3) which facilitates Akt phosphorylation. Thus, our data demonstrate that the PI3K/Akt signal transduction pathway mediates neuroblast migration after stroke. © 2003 Wiley‐Liss, Inc.
An inhibitor of mitochondrial complex I, rotenone, inactivates proteasome by oxidative modification and induces aggregation of oxidized proteins in SH‐SY5Y cells
Authors: Shamoto‐Nagai Masayo , Maruyama Wakako , Kato Yoji , Isobe Ken‐ichi , Tanaka Masashi , Naoi Makoto , Osawa Toshihiko 
Published: October 2003

AbstractIn Parkinson's disease, characteristic pathological features are the cell death of nigrostriatal dopamine neurons and the formation of Lewy bodies composed of oxidized proteins. Mitochondrial dysfunction and aggregation of abnormal proteins have been proposed to cause the pathological changes. However, the relation between these two factors remains to be clarified. In this study, the effects of mitochondrial dysfunction on the oxidative modification and accumulation of proteins were analyzed using an inhibitor of mitochondrial complex I, rotenone, and antibodies against acrolein‐ and dityrosine‐modified proteins. Under conditions inducing mainly apoptosis in neuroblastoma SH‐SY5Y cells, rotenone markedly increased oxidized proteins, especially those modified with acrolein, even though the increase in intracellular reactive oxygen and nitrogen species was only transient and was not so marked. In addition, the activity of the proteasome system degrading oxidized proteins was reduced profoundly after treatment with rotenone. The 20S β subunit of proteasome was modified with acrolein, to which other acrolein‐modified proteins were found to bind, as shown by coprecipitation with the antibody against 20S β subunit. These results suggest that mitochondrial dysfunction, especially decreased activity of complex I, may reduce proteasome activity through oxidative modification of proteasome itself and aggregation with other oxidized proteins. This mechanism might account for the accumulation of modified protein and, at least partially, for cell death of the dopamine neurons in Parkinson's disease. © 2003 Wiley‐Liss, Inc.
Novel roles of neuropeptide processing enzymes: EC3.4.24.15 in the neurome
Authors: Kim S.I. , Grum‐Tokars V. , Swanson T.A. , Cotter E.J. , Cahill P.A. , Roberts J.L. , Cummins P.M. , Glucksman M.J. 
Published: October 2003

AbstractNeuropeptide processing metalloenzymes, such as angiotensin converting enzyme, neprilysin, endothelin converting enzyme, neurolysin, and EC3.4.24.15 (EP24.15), are central to the formation and degradation of bioactive peptides. We present EP24.15 as a paradigm for novel functions ascribed to these enzymes in the neurome. Although the neurome typically encompasses proteomes of the brain and central nervous system, exciting new roles of these neuropeptidases have been demonstrated in other organ systems. We discuss the involvement of EP24.15 with clinical sequelae involving the use of gonadotropin‐releasing hormone (GnRH; LHRH) analogs that act as enzyme inhibitors, in vascular physiology (blood pressure regulation), and in the hematologic system (immune surveillance). Hemodynamic forces, such as cyclic strain and shear stress, on vascular cells, induce an increase in EP24.15 transcription, suggesting that neuropeptidase‐mediated hydrolysis of pressor/depressor peptides is likely regulated by changes in hemodynamic force and blood pressure. Lastly, EP24.15 regulates surface expression of major histocompatibility complex Class I proteins in vivo, suggesting that EP24.15 may play an important role in maintenance of immune privilege in sites of increased endogenous expression. In these extraneural systems, regulation of both neuropeptide and other peptide substrates by neuropeptidases indicates that the influence of these enzymes may be more global than was anticipated previously, and suggests that their attributed role as neuropeptidases underestimates their physiologic actions in the neural system. © 2003 Wiley‐Liss, Inc.
Decrease of morphine‐induced reward effects and withdrawal symptoms in mice overexpressing γ‐aminobutyric acid transporter I
Authors: Hu Jia‐Hua , Yang Na , Ma Ying‐Hua , Zhou Xiao‐Gang , Zhang Xu‐Ying , Jiang Jie , Mei Zhen‐Tong , Fei Jian , Guo Li‐He 
Published: October 2003

AbstractMorphine addiction has been shown to result from neural adaptations produced by repeated drug exposure, but the mechanism is still unclear. In the present study, we found that γ‐aminobutyric acid (GABA) uptake was increased in mouse brain 120 min after, but not 20 min after, morphine (10 mg/kg, s.c.) injection. We generated GABA transporter I (GAT1)‐overexpressing mice to investigate whether the GABAergic system and GABA transporter are involved in morphine‐induced reward effects and withdrawal symptoms. Our results revealed that the rewarding effects induced by morphine were significantly decreased in GAT1‐overexpressing mice as measured by the conditioned place preference (CPP) paradigm. Moreover, both somatic and vegetative signs of naloxone‐induced morphine withdrawal symptoms were substantially reduced in GAT1‐overexpressing mice. In addition, the decreased morphine rewarding in transgenic mice could be recovered when mice were coinjected with NO‐711 (a GAT1 selective inhibitor) in the CPP paradigm. These findings suggest that the GABAergic system plays an important role in morphine addiction and point to the possibility of developing drugs that target GAT1 and extend the clinical application of opiates. © 2003 Wiley‐Liss, Inc.
Mice lacking tissue plasminogen activator and urokinase plasminogen activator genes show attenuated matrix metalloproteases activity after sciatic nerve crush
Authors: Siconolfi Lisa B. , Seeds Nicholas W. 
Published: October 2003

AbstractPlasminogen activators (PAs), tissue PA (tPA) and urokinase PA (uPA), have been shown to be induced in sensory neurons after sciatic nerve crush. These findings suggested that PAs facilitate peripheral nerve regeneration by digesting adhesive cell contacts and by activation of other proteases, thereby initiating a proteolytic cascade. Both tPA and uPA activate some matrix metalloproteases (MMPs), indirectly via plasminogen activation or directly, such as the uPA activation of MMP‐2. In this study, we demonstrated, by using tPA and uPA knockout mice, that a lack of a plasminogen activator affected MMP‐9 and MMP‐2 activity after crushing of the sciatic nerve. These findings show that the PAs are important for MMP‐9 and MMP‐2 activity at the crush site. © 2003 Wiley‐Liss, Inc.
Treatment of chronically injured spinal cord with neurotrophic factors stimulates βII‐tubulin and GAP‐43 expression in rubrospinal tract neurons
Authors: Storer Paul D. , Dolbeare Dirk , Houle John D. 
Published: October 2003

AbstractExogenous neurotrophic factors provided at a spinal cord injury site promote regeneration of chronically injured rubrospinal tract (RST) neurons into a peripheral nerve graft. The present study tested whether the response to neurotrophins is associated with changes in the expression of two regeneration‐associated genes, βII‐tubulin and growth‐associated protein (GAP)‐43. Adult female rats were subjected to a right full hemisection lesion via aspiration of the C3 spinal cord. A second aspiration lesion was made 4 weeks later and gel foam saturated in brain‐derived neurotrophic factor (BDNF), glial cell‐line derived neurotrophic factor (GDNF), or phosphate‐buffered saline (PBS) was applied to the lesion site for 60 min. Using in situ hybridization, RST neurons were examined for changes in mRNA levels of βII‐tubulin and GAP‐43 at 1, 3, and 7 days after treatment. Based on analysis of gene expression in single cells, there was no effect of BDNF treatment on either βII‐tubulin or GAP‐43 mRNA expression at any time point. βII‐Tubulin mRNA levels were enhanced significantly at 1 and 3 days in animals treated with GDNF relative to levels in animals treated with PBS. Treatment with GDNF did not affect GAP‐43 mRNA levels at 1 and 3 days, but at 7 days there was a significant increase in mRNA expression. Interestingly, 7 days after GDNF treatment, the mean cell size of chronically injured RST neurons was increased significantly. Although GDNF and BDNF both promote axonal regeneration by chronically injured neurons, only GDNF treatment is associated with upregulation of βII‐tubulin or GAP‐43 mRNA. It is not clear from the present study how exogenous BDNF stimulates regrowth of injured axons. © 2003 Wiley‐Liss, Inc.