Apamin Attenuated Cerulein-Induced Acute Pancreatitis by Inhibition of JNK Pathway in Mice

Bae, Gi‐Sang; Heo, Kwang-Ho; Park, Kyoung-Chel; Choi, Sun Bok; Jo, Il‐Joo; Seo, Sang‐Woo; Kim, Dong-Goo; Shin, Joon-Yeon; Kang, Dae‐Gil; Lee, Ho-Sub; Song, Ho‐Joon; Shin, Byung‐Cheul; Park, Sung‐Joo

doi:10.1007/s10620-013-2800-0

Cited by 16 publications

(18 citation statements)

References 26 publications

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“…Bae et al [20] explored the possibility that apamin suppresses AP on acinal cells via SK channel regulation and the role of SK channels in AP in acinar cells. Bae et al [20] demonstrated evidence that apamin inhibits the development of AP by cerulein, a well-known substance that stimulates smooth muscles and induces digestion. Treatment with apamin in mice reduces serum amylase, lipase, cytokine, and myeloid oxidase activities.…”

Section: Pancreatitismentioning

confidence: 99%

“…Treatment with apamin in mice reduces serum amylase, lipase, cytokine, and myeloid oxidase activities. Based on Bae et al's study [20], the inhibitory effects of apamin have been demonstrated through c-Jun N-terminal kinases (JNK) inactivation in a cerulein-induced AP model in vivo. The administration of apamin inhibits the development of cerulein-induced AP, reducing inflammation, edema, cytokine production, and neutrophil infiltration in the pancreas.…”

Section: Pancreatitismentioning

confidence: 99%

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Therapeutic Effects of Apamin as a Bee Venom Component for Non-Neoplastic Disease

Han

Park

2020

Toxins

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Bee venom is a natural toxin produced by honeybees and plays an important role in defending bee colonies. Bee venom has several kinds of peptides, including melittin, apamin, adolapamine, and mast cell degranulation peptides. Apamin accounts for about 2%-3% dry weight of bee venom and is a peptide neurotoxin that contains 18 amino acid residues that are tightly crosslinked by two disulfide bonds. It is well known for its pharmacological functions, which irreversibly block Ca2+-activated K+ (SK) channels. Apamin regulates gene expression in various signal transduction pathways involved in cell development. The aim of this study was to review the current understanding of apamin in the treatment of apoptosis, fibrosis, and central nervous system diseases, which are the pathological processes of various diseases. Apamin's potential therapeutic and pharmacological applications are also discussed.

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Section: Pancreatitismentioning

confidence: 99%

Section: Pancreatitismentioning

confidence: 99%

Therapeutic Effects of Apamin as a Bee Venom Component for Non-Neoplastic Disease

Han

Park

2020

Toxins

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“…Following exposure to several stimulants, a series of the downstream molecules of NF-κB are activated, such as TNF-α, IL-10, IL-6, IL-1b, and iNOS. Studies have reported that cerulein induces NF-κB activation, thereby causing AP in vitro and in vivo [ 27 – 29 ]. In the present study, we found that cerulein stimulation promoted the phosphorylation of p65 and thus caused the activation of NF-κB in AR42J cells.…”

Section: Discussionmentioning

confidence: 99%

Protective Role of TNIP2 in Myocardial Injury Induced by Acute Pancreatitis and Its Mechanism

et al. 2017

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BackgroundAberrant regulation of nuclear factor-κB (NF-κB) and the signaling pathways that regulate its activity have been found to be involved in various pathologies, particularly cancers, as well as inflammatory and autoimmune diseases. Acute pancreatitis (AP) is a complex pathological process, depending on autodigestion caused by premature activation of zymogens. This study aimed to investigate the effect of high expression of TNIP2 gene on AP and AP-induced myocardial injury.Material/MethodsTo investigate the effect of TNIP2 on AP and AP-induced myocardial injury, we established an AP cell model and rat model. HE staining was applied for histological examination. ELISA was used to determine the level of pro-inflammatory cytokines (TNF-α and IL-6) and myocardial injury markers (LDH and CK-MB). QRT-PCR and Western blot analysis were performed to determine the mRNA and protein level of related genes, respectively.ResultsWe found that the protein level of TNIP2 was relatively higher in the normal AR42J cells. At 4 h after stimulating with cerulein, the protein level of TNIP2 decreased, reached a minimum at 8 h, and then gradually increased. We also found that TNIP2 was correlated with the activation of NF-κB in cerulein-stimulated AR42J cells, and TNIP2 over-expression inhibited the inflammatory response caused by cerulein. Moreover, our results suggest that TNIP2 over-expression relieved the cerulein-triggered inflammatory response and AP-induced myocardial injury in mice.ConclusionsTNIP2 was shown to exert a protective effect on AP and AP-induced myocardial injury.

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“…Through functional enrichment analysis, significant functions related to miR-24 were predicted: 'Positive regulation of calcium-mediated signaling', 'activation of JUN kinase activity', 'calcium ion transport', 'regulation of Rho protein signal transduction', 'negative regulation of protein kinase B signaling cascade', and 'T cell receptor signaling pathway'. Previous studies suggested that the dose-dependent inhibition of Rho-kinase had protective effects on AP, whereas bee venom could prevent AP and inhibit pancreatic acinar cell death through the inhibition of c-Jun N-terminal kinase activation (40,41). The phosphoinositide 3-kinase and protein kinase B signal transduction pathways may participate in the pathological process of lung injury in severe AP through the upregulation of NF-κB, tumor necrosis factor-α, and IL-lβ (18).…”

Section: Discussionmentioning

confidence: 99%

Screening and validation of differentially expressed extracellular miRNAs in acute pancreatitis

Meng

Wang

Xue

et al. 2017

Molecular Medicine Reports

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The present study aimed to screen for differentially expressed extracellular microRNAs (miRNAs) during the development of acute pancreatitis (AP) and validate the miRNA expression in the plasma of patients with AP. The culture medium of taurolithocholic acid‑3 sulfate‑treated rat pancreatic acinar AR42J cells was collected to extract total RNA for miRNA microarray analysis. Compared with the miRNA test results of the AP rats in the GEO databases, the differentially expressed extracellular miRNAs were screened. The TargetScan, miRanda, and PicTar programs were used for target gene prediction of the identified miRNAs, and gene ontology‑biological processes (GO‑BP) functional annotation was performed. Finally, the results from the combined microarray analyses (in vitro cell line and in vivo rat samples) were validated using plasma samples from patients with mild and moderately severe AP by reverse transcription‑polymerase chain reaction. The results demonstrated that extracellular miR‑24 was differentially expressed by microarray and bioinformatics analysis in both the cell line and the animal model of AP. Bioinformatics prediction analysis revealed that downstream target genes of miR‑24 included Vav2, Syk, Lhcgr, Slc9a3r1, Cacnb1, Cacna1b, Bcl10, and Fgd3. Functional enrichment analysis revealed that the main GO‑BP predicted functional presentations were positive regulation of calcium‑mediated signaling, activation of c‑Jun N‑terminal kinase activity, calcium ion transport, regulation of Rho protein signal transduction, negative regulation of the protein kinase B signaling cascade, and the T cell receptor signaling pathway. Validation analysis for the plasma miR‑24 expression in humans revealed a significant upregulation of miR‑24 in the plasma samples of AP patients compared with the healthy controls, while no significant difference was observed in the miR‑24 expression between the mild and the moderately severe AP groups. The present study confirmed the high expression of miR‑24 in peripheral blood during AP, suggesting that miR‑24 might have an intercellular communication role contributing to the AP‑associated distant organ injury.

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Apamin Attenuated Cerulein-Induced Acute Pancreatitis by Inhibition of JNK Pathway in Mice

Abstract: These results could suggest that apamin could protect against AP by inhibition of JNK activation.

Cited by 16 publications

References 26 publications

Therapeutic Effects of Apamin as a Bee Venom Component for Non-Neoplastic Disease

Therapeutic Effects of Apamin as a Bee Venom Component for Non-Neoplastic Disease

Protective Role of TNIP2 in Myocardial Injury Induced by Acute Pancreatitis and Its Mechanism

Screening and validation of differentially expressed extracellular miRNAs in acute pancreatitis

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