Spautin-A41 Attenuates Cerulein-Induced Acute Pancreatitis through Inhibition of Dysregulated Autophagy

Dong, Kai; Xia, Chen; Xie, Liping; Yu, Lanting; Shen, Min; Wang, Yanping; Wu, Shanshan; Wang, Jiajia; Lu, Junxi; Wei, Gang; Xu, Danfeng; Liu, Yang

doi:10.1248/bpb.b19-00132

Cited by 10 publications

(5 citation statements)

References 69 publications

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“…Moreover, a spautin-1 derivative, spautin-A41, was described as a potent autophagy inhibitor. Mice treated with spautin-A41 were resistant to cerulein-induced pancreatitis due to the inhibition of autophagosome formation [450]. Interestingly, sitagliptin, a dipeptidyl peptidase-4 (DPP4) inhibitor recently associated with autophagy, ameliorated AP-induced acute lung injury.…”

Section: Future Perspectivesmentioning

confidence: 99%

The Pathogenesis of Pancreatitis and the Role of Autophagy

Tsomidis,

Voumvouraki,

Kouroumalis

2024

Gastroenterology Insights

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The pathogenesis of acute and chronic pancreatitis has recently evolved as new findings demonstrate a complex mechanism operating through various pathways. In this review, the current evidence indicating that several mechanisms act in concert to induce and perpetuate pancreatitis were presented. As autophagy is now considered a fundamental mechanism in the pathophysiology of both acute and chronic pancreatitis, the fundamentals of the autophagy pathway were discussed to allow for a better understanding of the pathophysiological mechanisms of pancreatitis. The various aspects of pathogenesis, including trypsinogen activation, ER stress and mitochondrial dysfunction, the implications of inflammation, and macrophage involvement in innate immunity, as well as the significance of pancreatic stellate cells in the development of fibrosis, were also analyzed. Recent findings on exosomes and the miRNA regulatory role were also presented. Finally, the role of autophagy in the protection and aggravation of pancreatitis and possible therapeutic implications were reviewed.

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Section: Future Perspectivesmentioning

confidence: 99%

The Pathogenesis of Pancreatitis and the Role of Autophagy

Tsomidis,

Voumvouraki,

Kouroumalis

2024

Gastroenterology Insights

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“…Small-molecule inhibitor Spautin-1 can increase the ubiquitination level of Beclin1 subunit in VPS34-PI3K kinase complex and promote its degradation by suppressing the activities of USP10 and USP13, thus preventing the process of cell autophagy. The combination of DUBs inhibitors and anticancer drugs can enhance the sensitivity of tumor cells to drugs (Shao et al, 2014;Schott et al, 2018;Yeo et al, 2018;Dong et al, 2019). The treatment of H1299 lung cancer cells with LDN-57444, a small-molecule inhibitor targeting UCH-L1, significantly decreased the proliferation rate of tumor cells (Liu et al, 2003).…”

Section: Small-molecule Inhibitors Of Dubsmentioning

confidence: 99%

A review of deubiquitinases and thier roles in tumorigenesis and development

Liang,

Wang,

Liu

et al. 2023

Front. Bioeng. Biotechnol.

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Ubiquitin is a small protein that can be added onto target protein for inducing target degradation, thereby modulating the activity and stability of protein. Relatively, deubiquitinases (DUBs), a class catalase that can remove ubiquitin from substrate protein, provide a positive regulation of the protein amount at transcription level, post-translational modification, protein interaction, etc. The reversible and dynamic ubiquitination-deubiquitination process plays an essential role in maintaining protein homeostasis, which is critical to almost all the biological processes. Therefore, the metabolic dysregulation of deubiquitinases often lead to serious consequences, including the growth and metastasis of tumors. Accordingly, deubiquitinases can be served as key drug targets for the treatment of tumors. The small molecule inhibitors targeting deubiquitinases has become one of the hot spots of anti-tumor drug research areas. This review concentrated on the function and mechanism of deubiquitinase system in the proliferation, apoptosis, metastasis and autophagy of tumor cells. The research status of small molecule inhibitors of specific deubiquitinases in tumor treatment is introduced, aiming to provide reference for the development of clinical targeted drugs.

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“…In addition, targeted autophagy can provide therapeutic targets for AP (30). For example, spautin-a41 reduces cerulein-induced acute pancreatitis by inhibiting dysregulated autophagy (31). β1 syntrophin protects cerulein-induced acute pancreatitis via modulating autophagy initiation.…”

Section: Construction Of Mirna-mrna Regulation Network In Apmentioning

confidence: 99%