ER stress-associated CTRC mutants decrease stimulated pancreatic zymogen secretion through SIRT2-mediated microtubule dysregulation

Binker, Marcelo Gustavo; Richards, Daniel A.; Gaisano, Herbert Y.; Cosen-Binker, Laura Iris

doi:10.1016/j.bbrc.2015.05.064

Cited by 10 publications

(6 citation statements)

References 26 publications

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“…In addition, there are a variety of protective mechanisms against premature zymogen activation in vivo through the inhibition or degradation of activated trypsin (Hirota et al, 2006; Binker et al, 2015). These mechanisms include inhibition by pancreatic secretory trypsin inhibitor (PSTI), also known as a serine protease inhibitor Kazal-type 1 (SPINK1) or tumor-associated trypsin inhibitor (TATI) (Hirota et al, 2006), and degradation by chymotrypsin-C (CTRC) (Binker et al, 2015) and the lysosomal hydrolase cathepsin-L (Wartmann et al, 2010).…”

Section: Underlying Mechanisms Of Apmentioning

confidence: 99%

“…These mechanisms include inhibition by pancreatic secretory trypsin inhibitor (PSTI), also known as a serine protease inhibitor Kazal-type 1 (SPINK1) or tumor-associated trypsin inhibitor (TATI) (Hirota et al, 2006), and degradation by chymotrypsin-C (CTRC) (Binker et al, 2015) and the lysosomal hydrolase cathepsin-L (Wartmann et al, 2010). Once these protective mechanisms are expended, there is an increased risk of developing AP.…”

Section: Underlying Mechanisms Of Apmentioning

confidence: 99%

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Chinese Herbal Medicines Attenuate Acute Pancreatitis: Pharmacological Activities and Mechanisms

Xiang

Zhang

et al. 2017

Front. Pharmacol.

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Acute pancreatitis (AP) is a commonly occurring gastrointestinal disorder. An increase in the annual incidence of AP has been observed, and it causes acute hospitalization and high mortality. The diagnosis and treatment guidelines for AP recommend conservative medical treatments focused on reducing pancreatic secretion and secondary injury, as a primary therapeutic approach. Unfortunately, the existing treatment options have limited impact on the incidence and severity of AP due to the complex and multifaceted pathological process of this disease. In recent decades, Chinese herbal medicines (CHMs) have been used as efficient therapeutic agents to attenuate AP in Asian countries. Despite early cell culture, animal models, and clinical trials, CHMs are capable of interacting with numerous molecular targets participating in the pathogenesis of AP; however, comprehensive, up-to-date communication in this field is not yet available. This review focuses on the pharmacological activities of CHMs against AP in vitro and in vivo and the underlying mechanisms. A computational prediction of few selected and promising plant-derived molecules (emodin, baicalin, resveratrol, curcumin, ligustrazine, and honokiol) to target numerous proteins or networks involved in AP was initially established based on a network pharmacology simulation. Moreover, we also summarized some potential toxic natural products for pancreas in order to more safe and reasonable medication. These breakthrough findings may have important implications for innovative drug research and the future development of treatments for AP.

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Section: Underlying Mechanisms Of Apmentioning

confidence: 99%

Section: Underlying Mechanisms Of Apmentioning

confidence: 99%

Chinese Herbal Medicines Attenuate Acute Pancreatitis: Pharmacological Activities and Mechanisms

Xiang

Zhang

et al. 2017

Front. Pharmacol.

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“…Enzyme activities were calculated as units per milligram (U/mg) of protein. The content of protein was detected by using the bicinchoninic acid (BCA) method (Binker et al, 2015).…”

Section: Determination Of Cellular Antioxidant Enzymesmentioning

confidence: 99%

Charge properties of peptides derived from casein affect their bioavailability and cytoprotection against H2O2-induced oxidative stress

Wang

Xie

Лі

2016

Journal of Dairy Science

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The effects of charge properties of casein peptides on absorption stability, antioxidant activity, and cytoprotection were evaluated. Alcalase hydrolysates of casein were separated into 4 fractions by cation-exchange chromatography according to charge properties. After simulated digestion and Caco-2 cell transmembrane transport, we determined the total antioxidant capacity (Trolox equivalent antioxidative capacity and oxygen radical antioxidant activity) and nitrogen content of peptide fractions to estimate available antioxidant efficacy and bioavailability (BA) of peptides. Results showed that negatively charged peptide fractions had greater BA and antioxidant activities after digestion and absorption. The peptide permeates were used to test the cytoprotective effect against H2O2-induced oxidative damage in HepG-2 cells. All peptide permeates increased cell viability, elevated catalase activity, and decreased superoxide dismutase activity. However, negatively charged peptide fractions preserved cell viability to a greater degree. Therefore, the negatively charged peptides from casein may be potential antioxidants and could be used as ingredients in functional foods and dietary supplements.

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“…Pancreatic cells can produce the corresponding ERS response under the stimulation from different secretagogues. The expression of mutant chymotrypsin, which is associated with hereditary pancreatitis, leading to the accumulation of a large amount of misfolded CTRC in the ER and further deterioration due to ERS, ultimately regulating trypsin secretion through the ERS pathway . Cholecystokinin can act on pancreatic acinus in AP and regulate PERK to enable eIF2α phosphorylation and inhibit protein synthesis …”

Section: Ers and Apmentioning

confidence: 99%

“…The expression of mutant chymotrypsin, which is associated with hereditary pancreatitis, leading to the accumulation of a large amount of misfolded CTRC in the ER and further deterioration due to ERS, 79 ultimately regulating trypsin secretion through the ERS pathway. 80 Cholecystokinin can act on pancreatic acinus in AP and regulate PERK to enable eIF2α phosphorylation and inhibit protein synthesis. 77 Zymophagy is an endogenous protective mechanism of the pancreas that was newly discovered by in AP in 2011.…”

Section: Trypsinogen and Zymophagymentioning

confidence: 99%

Endoplasmic reticulum stress is activated in acute pancreatitis

Chen

et al. 2016

J of Digest Diseases

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Endoplasmic reticulum (ER) is one of the most important cell organelles in the body, regulating protein synthesis, folding and aggregation. Endoplasmic reticulum stress (ERS) is a particular subcellular pathological process involving an imbalance of homeostasis and ER disorder. In the early stage of ERS, cells show a protective unfolded protein response that changes the cellular transcriptional and translational programs to alleviate the process. Therefore, a certain degree of ERS can activate the protective adaptation of cells, whereas sustained severe ERS triggers an apoptotic signal and leads to apoptosis. Acute pancreatitis is a disease caused by trypsin digestion of the pancreas, although the pathogenesis is not completely understood. However, a close association has been suggested between pancreatitis and ERS. This article reviewed relevant research advances and discussed the effect of ERS on the development and progression of acute pancreatitis.

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ER stress-associated CTRC mutants decrease stimulated pancreatic zymogen secretion through SIRT2-mediated microtubule dysregulation

Cited by 10 publications

References 26 publications

Chinese Herbal Medicines Attenuate Acute Pancreatitis: Pharmacological Activities and Mechanisms

Chinese Herbal Medicines Attenuate Acute Pancreatitis: Pharmacological Activities and Mechanisms

Charge properties of peptides derived from casein affect their bioavailability and cytoprotection against H2O2-induced oxidative stress

Endoplasmic reticulum stress is activated in acute pancreatitis

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