Modulation of gastric mucosal calcium channel activity by mucus glycoprotein |
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| Institution: | 1. Hefei National Lab for Physical Sciences at the Microscale and the Centers for Biomedical Engineering, University of Science and Technology of China, Hefei, Anhui, 230027, China;2. Department of Chemistry, Government College Women University, Faisalabad, 38000, Pakistan;3. Aga Khan University Hospital Laboratory Specimen Collection Unit, Faisalabad, 38000, Pakistan;4. Division of Life Sciences and Medicine, Cancer Research Center, The First Affiliated Hospital of University of Science and Technology of China, University of Science and Technology of China, Hefei, Anhui, 230036, China;5. School of Life Science and Food Engineering, Huaiyin Institute of Technology, Huaian, 223003, China;6. Professor of Pathology, Al-Nafees Medical College and Hospital, Isra University, Islamabad, 45600, Pakistan;1. Laboratory of Insect Virology, Department of Biochemistry and Molecular Biology, Federal University of Santa Maria, Santa Maria, RS, 97105-900, Brazil;2. Laboratory of Biochemistry, Department of Biochemistry and Molecular Biology, Federal University of Santa Maria, Santa Maria, RS, 97105-900, Brazil;1. Marine and Freshwater Research Centre, Galway-Mayo Institute of Technology, Dublin Road, Galway, Co. Galway, Ireland;2. FishVet Group Ireland, Unit 7b Oranmore Business Park, Oranmore, Co. Galway, Ireland;3. Department of Cell Biology and Histology, Faculty of Biology, Campus Regional de Excelencia Internacional “Campus Mare Nostrum”, University of Murcia, Murcia, Spain;1. Department of Oral Science, Graduate School of Medicine, Chiba University, Chiba, Japan;2. Department of Dentistry and Oral-Maxillofacial Surgery, Chiba University Hospital, Chiba, Japan;3. Division of Oral Surgery, Eastern Chiba Medical Center, Chiba, Japan;4. Division of Oral Surgery, Chiba Rosai Hospital, Chiba, Japan;5. Division of Dentistry, Chiba Prefectural Sawara Hospital, Chiba, Japan;6. Department of Medical Oncology, Graduate School of Medicine, Chiba University, Chiba, Japan |
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| Abstract: | - 1.1. The effect of gastric mucus glycoprotein on the activity of calcium channel isolated from gastric epithelial cell membrane was investigated. The 45Ca2+ uptake into the vesicle-reconstituted channels, while only moderately (14%) affected by the intact mucus glycoprotein, was found significantly inhibited (59%) by the acidic glycoprotein fraction. This effect was associated with the sialic acid and sulfate ester groups of the glycoprotein, as their removal caused a loss in the inhibition.
- 2.2. The channel complex in the presence of epidermal growth factor (EGF) and ATP responded by an increase in protein tyrosine phosphorylation of 55 and 170 kDa proteins, and the vesicles containing the phosphorylated channels showed a 50% increase in 45Ca2+ uptake. The phosphorylation and the calcium uptake were susceptible to inhibition by a specific tyrosine kinase inhibitor, genistein.
- 3.3. The channel protein phosphorylation was inhibited by the acidic mucus glycoprotein, which also interfered with the binding of EGF to the channel protein. The inhibitory effect was dependent upon the presence of sulfate ester and sialic acid groups, as evidenced by the loss of the glycoprotein inhibitory capacity following their removal.
- 4.4. The results suggest that the acidic gastric mucus glycoproteins, by modulating the EGF-controlled calcium channel phosphorylation, play a major role in gastric mucosal calcium homeostasis.
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