Endoplasmic reticulum stress is activated in acute pancreatitis

Wu, Jian; Li, Wei Min; Chen, Yi Na; Zhao, Qian; Chen, Qin Fen

doi:10.1111/1751-2980.12347

Cited by 42 publications

(28 citation statements)

References 92 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The development of SAP is a complex process that initiates in the pancreatic acinar cells and is characterized by inflammation response and cell death, usually accompanying disorder of endocrine function as a result of pancreatic islet injury [ 29 , 30 ]. ER stress and its responses participate in the development of acute pancreatitis [ 31 ]. Under the circumstance of unresolved and severe ER stress, persistent activation of the UPR may destroy the pancreatic acinar cell and beta-cell homeostasis that constantly end in cell death owing to accumulation of misfolded or unfolded proteins and subsequently result in release of digestive enzymes and inflammatory cytokines, as well as insulin [ 32 , 33 ].…”

Section: Discussionmentioning

confidence: 99%

4-Phenylbutyric Acid Attenuates Pancreatic Beta-Cell Injury in Rats with Experimental Severe Acute Pancreatitis

Hong

Wang

et al. 2016

International Journal of Endocrinology

View full text Add to dashboard Cite

Endoplasmic reticulum (ER) stress is a particular process with an imbalance of homeostasis, which plays an important role in pancreatitis, but little is known about how ER stress is implicated in severe acute pancreatitis (SAP) induced pancreatic beta-cell injury. To investigate the effect of 4-phenylbutyric acid (4-PBA) on the beta-cell injury following SAP and the underlying mechanism, twenty-four Sprague-Dawley rats were randomly divided into sham-operation (SO) group, SAP model group, and 4-PBA treatment group. SAP model was induced by infusion of 5% sodium taurocholate into the biliopancreatic duct. 4-PBA or normal saline was injected intraperitoneally for 3 days in respective group before successful modeling. Results showed that 4-PBA attenuated the following: (1) pancreas and islet pathological injuries, (2) serum TNF-α and IL-1β, (3) serum insulin and glucose, (4) beta-cell ultrastructural changes, (5) ER stress markers (BiP, ORP150, and CHOP), Caspase-3, and insulin expression in islet. These results suggested that 4-PBA mitigates pancreatic beta-cell injury and endocrine disorder in SAP, presumably because of its role in inhibiting excessive endoplasmic reticulum stress. This may serve as a new therapeutic target for reducing pancreatic beta-cell injury and endocrine disorder in SAP upon 4-PBA treatment.

show abstract

Section: Discussionmentioning

confidence: 99%

4-Phenylbutyric Acid Attenuates Pancreatic Beta-Cell Injury in Rats with Experimental Severe Acute Pancreatitis

Hong

Wang

et al. 2016

International Journal of Endocrinology

View full text Add to dashboard Cite

show abstract

“…As presented in Figure 2 , the pathogenesis of AP seems to be related to a series of complex and multifaceted pathological processes, involving pancreatic self-digestion (Lerch and Gorelick, 2000), inflammatory response, oxidative stress (Xiang et al, 2016), intracellular calcium overload, endoplasmic reticulum (ER) stress (Wu J.S. et al, 2016), pancreatic acinar cell apoptosis and necrosis (Xiang et al, 2016), and microcirculation disorder (Tomkotter et al, 2016).…”

Section: Underlying Mechanisms Of Apmentioning

confidence: 99%

Chinese Herbal Medicines Attenuate Acute Pancreatitis: Pharmacological Activities and Mechanisms

Xiang

Zhang

et al. 2017

Front. Pharmacol.

View full text Add to dashboard Cite

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.

show abstract

“…Interestingly, we found a correlation between the degree of endocytosed CEL-HYB and CEL-MODY proteins and cell viability ( Figures 1-3 and 5). A high uptake of aggregated proteins might trigger ER stress and disturb ER homeostasis, ultimately leading to apoptosis [32,33]. This was recently supported by Xiao et al [31], who reported that intracellular CEL-MODY aggregates generated ER stress and induced apoptosis.…”

Section: Discussionmentioning

confidence: 86%

Pathogenic Carboxyl Ester Lipase (CEL) Variants Interact with the Normal CEL Protein in Pancreatic Cells

Dalva

Lavik

Jellas

et al. 2020

Cells

View full text Add to dashboard Cite

Mutations in the gene encoding the digestive enzyme carboxyl ester lipase (CEL) are linked to pancreatic disease. The CEL variant denoted CEL-HYB predisposes to chronic pancreatitis, whereas the CEL-MODY variant causes MODY8, an inherited disorder of endocrine and exocrine pancreatic dysfunction. Both pathogenic variants exhibit altered biochemical and cellular properties compared with the normal CEL protein (CEL-WT, wild type). We here aimed to investigate effects of CEL variants on pancreatic acinar and ductal cell lines. Following extracellular exposure, CEL-HYB, CEL-MODY, and CEL-WT were endocytosed. The two pathogenic CEL proteins significantly reduced cell viability compared with CEL-WT. We also found evidence of CEL uptake in primary human pancreatic acinar cells and in native ductal tissue. Moreover, coexpression of CEL-HYB or CEL-MODY with CEL-WT affected secretion of the latter, as CEL-WT was observed to accumulate intracellularly to a higher degree in the presence of either pathogenic variant. Notably, in coendocytosis experiments, both pathogenic variants displayed a modest effect on cell viability when CEL-WT was present, indicating that the normal protein might diminish toxic effects conferred by CEL-HYB and CEL-MODY. Taken together, our findings provide valuable insight into how the pathogenic CEL variants predispose to pancreatic disease and why these disorders develop slowly over time.

show abstract

Endoplasmic reticulum stress is activated in acute pancreatitis

Cited by 42 publications

References 92 publications

4-Phenylbutyric Acid Attenuates Pancreatic Beta-Cell Injury in Rats with Experimental Severe Acute Pancreatitis

4-Phenylbutyric Acid Attenuates Pancreatic Beta-Cell Injury in Rats with Experimental Severe Acute Pancreatitis

Chinese Herbal Medicines Attenuate Acute Pancreatitis: Pharmacological Activities and Mechanisms

Pathogenic Carboxyl Ester Lipase (CEL) Variants Interact with the Normal CEL Protein in Pancreatic Cells

Contact Info

Product

Resources

About