دورية أكاديمية
Ca2+ Influx Channel Inhibitor SARAF Protects Mice From Acute Pancreatitis
| العنوان: | Ca2+ Influx Channel Inhibitor SARAF Protects Mice From Acute Pancreatitis |
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| المساهمون: | Aran Son, Malini Ahuja, Daniella M. Schwartz, Arpad Varga, William Swaim, Namju Kang, Jozsef Maleth, Dong Min Shin, Shmuel Muallem, Shin, Dong Min |
| بيانات النشر: | W.B. Saunders |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Acinar Cells/pathology, Animals, Calcium/metabolism, Ceruletide/toxicity, Disease Models, Animal, HEK293 Cells, Humans, Intracellular Calcium-Sensing Proteins/genetics, Intracellular Calcium-Sensing Proteins/metabolism, Membrane Proteins/genetics, Membrane Proteins/metabolism, Mice, Knockout, Neoplasm Proteins/metabolism, Pancreas/cytology, Pancreas/pathology, Pancreatitis/blood, Pancreatitis/chemically induced, Pancreatitis/pathology, Severity of Illness Index, Stromal Interaction Molecule 1/metabolism, Calcium, Injury, Pancreas, SARAF |
| الوصف: | BACKGROUND & AIMS: Pancreatitis is characterized by increased influx of Ca2+ into acinar cells, by unknown mechanisms. Inhibitors of Ca2+ influx channels could be effective in treating acute pancreatitis, but these have deleterious side effects that can result in death. We investigated the expression patterns and functions of acinar cell Ca2+ channels and factors that regulate them during development of acute pancreatitis, along with changes in the channel inactivator store-operated calcium entry-associated regulatory factor (SARAF). We investigated whether SARAF is a target for treatment of acute pancreatitis and its status in human with pancreatitis. METHODS: We generated mice that expressed SARAF tagged with hemagglutinin, using CRISPR/Cas9 gene editing, and isolated acinar cells. We also performed studies with Saraf-/- mice, Sarafzf/zf mice, mice without disruption of Saraf (control mice), and mice that overexpress fluorescently labeled SARAF in acinar cells. We analyzed interactions between stromal interaction molecule 1 (STIM1) and SARAF in HEK cells stimulated with carbachol using fluorescence resonance energy transfer microscopy and immunoprecipitation. Mice were given injections of caerulein or L-arginine to induce pancreatitis. Pancreatic tissues and blood samples were collected and levels of serum amylase, trypsin, tissue damage, inflammatory mediators, and inflammatory cells were measured. We performed quantitative polymerase chain reaction analyses of pancreatic tissues from 6 organ donors without pancreatic disease (controls) and 8 patients with alcohol-associated pancreatitis. RESULTS: Pancreatic levels of Ca2+ influx channels or STIM1 did not differ significantly between acinar cells from mice with vs. without pancreatitis. By contrast, pancreatic levels of Saraf messenger RNA and SARAF protein initially markedly increased but then decreased during cell stimulation or injection of mice with caerulein, resulting in excessive Ca2+ influx. STIM1 interacted stably with SARAF following stimulation ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 0016-5085 1528-0012 |
| العلاقة: | GASTROENTEROLOGY; J00917; OAK-2019-06597; https://ir.ymlib.yonsei.ac.kr/handle/22282913/174552Test; https://www.sciencedirect.com/science/article/pii/S0016508519412997Test; T201904863; GASTROENTEROLOGY, Vol.157(6) : 1660-1672.e2, 2019 |
| DOI: | 10.1053/j.gastro.2019.08.042 |
| الإتاحة: | https://doi.org/10.1053/j.gastro.2019.08.042Test https://ir.ymlib.yonsei.ac.kr/handle/22282913/174552Test https://www.sciencedirect.com/science/article/pii/S0016508519412997Test |
| حقوق: | CC BY-NC-ND 2.0 KR |
| رقم الانضمام: | edsbas.506531ED |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 00165085 15280012 |
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| DOI: | 10.1053/j.gastro.2019.08.042 |