Functional Transformation of Gastric Parietal Cells and Intracellular Trafficking of Ion Channels/Transporters in the Apical Canalicular Membrane Associated with Acid Secretion

Aoyama, Fumiyo; Sawaguchi, Akira

doi:10.1248/bpb.34.813

Cited by 12 publications

(8 citation statements)

References 38 publications

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“…A comparison of SPECT/CT images from AA and WT mice revealed greater accumulation of 125 I-p5+14 in the amyloid-laden spleen, liver and intestines at all time points. Dehalogenation of the radioiodinated p5+14, which occurs intracellularly in the renal proximal tubules (and to a lesser extent, hepatocytes) as a consequence of catabolism [ 43 ], liberated free radioiodide which was then sequestered by halide symporters in the stomach [ 44 ] and thyroid.…”

Section: Resultsmentioning

confidence: 99%

Preclinical Validation of the Heparin-Reactive Peptide p5+14 as a Molecular Imaging Agent for Visceral Amyloidosis

et al. 2015

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Amyloid is a complex pathologic matrix comprised principally of paracrystalline protein fibrils and heparan sulfate proteoglycans. Systemic amyloid diseases are rare, thus, routine diagnosis is often challenging. The glycosaminoglycans ubiquitously present in amyloid deposits are biochemically and electrochemically distinct from those found in the healthy tissues due to the high degree of sulfation. We have exploited this unique property and evaluated heparin-reactive peptides, such as p5+14, as novel agents for specifically targeting and imaging amyloid. Herein, we demonstrate that radiolabeled p5+14 effectively bound murine AA amyloid in vivo by using molecular imaging. Biotinylated peptide also reacted with the major forms of human amyloid in tissue sections as evidenced immunohistochemically. Furthermore, we have demonstrated that the peptide also binds synthetic amyloid fibrils that lack glycosaminoglycans implying that the dense anionic OPEN ACCESSMolecules 2015, 20 7658 motif present on heparin is mimicked by the amyloid protein fibril itself. These biochemical and functional data support the translation of radiolabeled peptide p5+14 for the clinical imaging of amyloid in patients.

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Section: Resultsmentioning

confidence: 99%

Preclinical Validation of the Heparin-Reactive Peptide p5+14 as a Molecular Imaging Agent for Visceral Amyloidosis

et al. 2015

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“…This process is far more efficient than the organification of 124 I in the thyroid as evidenced by the difference in the rate of uptake by these two organs over 120 min pi. It may be that the stomach, due to its larger mass, dominates the removal of iodide from the circulation, or it could be due to the relative expression of halide transport proteins in the thyroid (Na/I symporters) and the stomach (numerous chloride channel transporters [2]).…”

Section: Discussionmentioning

confidence: 99%

Dynamic PET and SPECT imaging with radioiodinated, amyloid-reactive peptide p5 in mice: A positive role for peptide dehalogenation

et al. 2014

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Dynamic molecular imaging provides bio-kinetic data that is used to characterize novel radiolabeled tracers for the detection of disease. Amyloidosis is a rare protein misfolding disease that can affect many organs. It is characterized by extracellular deposits composed principally of fibrillar proteins and hypersulfated proteoglycans. We have previously described a peptide, p5, which binds preferentially to amyloid deposits in a murine model of reactive (AA) amyloidosis. We have determined the whole body distribution of amyloid by molecular imaging techniques using radioiodinated p5. The loss of radioiodide from imaging probes due to enzymatic reaction has plagued the use of radioiodinated peptides and antibodies. Therefore, we studied iodine-124-labeled p5 by using dynamic PET imaging of both amyloid-laden and healthy mice to assess the rates of amyloid binding, the relevance of dehalogenation and the fate of the radiolabeled peptide. Rates of blood pool clearance, tissue accumulation and dehalogenation of the peptide were estimated from the images. Comparisons of these properties between the amyloid-laden and healthy mice provided kinetic profiles whose differences may prove to be indicative of the disease state. Additionally, we performed longitudinal SPECT/CT imaging with iodine-125-labeled p5 up to 72 hours post injection to determine the stability of the radioiodinated peptide when bound to the extracellular amyloid. Our data show that amyloid-associated peptide, in contrast to the unbound peptide, is resistant to dehalogenation resulting in enhanced amyloid-specific imaging. These data further support the utility of this peptide for detecting amyloidosis and monitoring potential therapeutic strategies in patients.

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“…Moreover, CLC-2 can be activated by protein kinase C [77]. Secretagogue stimulation results in a major rapid morphological transformation in parietal cells, which is essential for maximal acid secretion; in this process, cytoplasmic tubulovesicles containing H + /K + -ATPase (and perhaps Cl − and K + channels/transporters) fuse with the apical membrane to form a greatly expanded secretory canaliculus with Evidence-Based Complementary and Alternative Medicine 3 increased elongated microvilli that are recycled during the resting stage [13,78,79]. CLC-2 localized to gastric parietal cells in isolated rabbit gastric glands showed similar localization to H + /K + -ATPase and was important for gastric parietal cell acid secretion [80].…”

Section: Physiological Function Of Clc-2 In the Stomachmentioning

confidence: 99%

Physiological Significance of Ion Transporters and Channels in the Stomach and Pathophysiological Relevance in Gastric Cancer

Yuan

Tuo

et al. 2020

Evidence-Based Complementary and Alternative Medicine

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Gastric cancer (GC) is a highly invasive and fatal malignant disease that accounts for 5.7% of new global cancer cases and is the third leading cause of cancer-related death. Acid/base homeostasis is critical for organisms because protein and enzyme function, cellular structure, and plasma membrane permeability change with pH. Various ion transporters are expressed in normal gastric mucosal epithelial cells and regulate gastric acid secretion, ion transport, and fluid absorption, thereby stabilizing the differentiation and homeostasis of gastric mucosal epithelial cells. Ion transporter dysfunction results in disordered ion transport, mucosa barrier dysfunction, and acid/base disturbances, causing gastric acid-related diseases such as chronic atrophic gastritis (CAG) and GC. This review summarizes the physiological functions of multiple ion transporters and channels in the stomach, including Cl− channels, Cl−/HCO3− exchangers, sodium/hydrogen exchangers (NHEs), and potassium (K+) channels, and their pathophysiological relevance in GC.

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Functional Transformation of Gastric Parietal Cells and Intracellular Trafficking of Ion Channels/Transporters in the Apical Canalicular Membrane Associated with Acid Secretion

Cited by 12 publications

References 38 publications

Preclinical Validation of the Heparin-Reactive Peptide p5+14 as a Molecular Imaging Agent for Visceral Amyloidosis

Preclinical Validation of the Heparin-Reactive Peptide p5+14 as a Molecular Imaging Agent for Visceral Amyloidosis

Dynamic PET and SPECT imaging with radioiodinated, amyloid-reactive peptide p5 in mice: A positive role for peptide dehalogenation

Physiological Significance of Ion Transporters and Channels in the Stomach and Pathophysiological Relevance in Gastric Cancer

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