Next Article in Journal
Complexity and Specificity of Sec61-Channelopathies: Human Diseases Affecting Gating of the Sec61 Complex
Next Article in Special Issue
Extracellular Vesicle Surface Signatures in IPF Patients: A Multiplex Bead-Based Flow Cytometry Approach
Previous Article in Journal
Next Generation Therapeutics for the Treatment of Myelofibrosis
Previous Article in Special Issue
Transmembrane and Tetratricopeptide Repeat Containing 4 Is a Novel Diagnostic Marker for Prostate Cancer with High Specificity and Sensitivity
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
Cells
Volume 10
Issue 5
10.3390/cells10051035
cells-logo
Submit to this Journal Review for this Journal Propose a Special Issue
► Article Menu

Article Menu

share Share announcement Help format_quote Cite question_answer Discuss in SciProfiles
first_page
settings
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Article

Protective Effects of Necrostatin-1 in Acute Pancreatitis: Partial Involvement of Receptor Interacting Protein Kinase 1

by
Yulin Ouyang
1,2,
Li Wen
3,
Jane A. Armstrong
3,
Michael Chvanov
1,
Diane Latawiec
3,
Wenhao Cai
3,
Mohammad Awais
3,
Rajarshi Mukherjee
3,
Wei Huang
3,
Peter J. Gough
4,
John Bertin
4,
Alexei V. Tepikin
1,
Robert Sutton
3 and
David N. Criddle
1,*
1
Department of Molecular Physiology & Cell Signalling, Institute of Systems, Molecular & Integrative Biology, University of Liverpool, Liverpool L69 3BX, UK
2
Brain Cognition and Brain Disease Institute, Chinese Academy of Sciences, Shenzhen 518055, China
3
Molecular & Clinical Cancer Medicine, Institute of Systems, Molecular & Integrative Biology, University of Liverpool, Liverpool L69 3BX, UK
4
Pattern Recognition Receptor Discovery Performance Unit, Immuno-Inflammation Therapeutic Area, GlaxoSmithKline, Collegeville, PA 19426, USA
*
Author to whom correspondence should be addressed.
Cells 2021, 10(5), 1035; https://doi.org/10.3390/cells10051035
Submission received: 8 March 2021 / Revised: 22 April 2021 / Accepted: 23 April 2021 / Published: 27 April 2021
(This article belongs to the Special Issue 10th Anniversary of Cells—Advances in Cellular Pathology)
Browse Figures
Versions Notes

Abstract

Acute pancreatitis (AP) is a severe and potentially fatal disease caused predominantly by alcohol excess and gallstones, which lacks a specific therapy. The role of Receptor-Interacting Protein Kinase 1 (RIPK1), a key component of programmed necrosis (Necroptosis), is unclear in AP. We assessed the effects of RIPK1 inhibitor Necrostatin-1 (Nec-1) and RIPK1 modification (RIPK1K45A: kinase dead) in bile acid (TLCS-AP), alcoholic (FAEE-AP) and caerulein hyperstimulation (CER-AP) mouse models. Involvement of collateral Nec-1 target indoleamine 2,3-dioxygenase (IDO) was probed with the inhibitor Epacadostat (EPA). Effects of Nec-1 and RIPK1K45A were also compared on pancreatic acinar cell (PAC) fate in vitro and underlying mechanisms explored. Nec-1 markedly ameliorated histological and biochemical changes in all models. However, these were only partially reduced or unchanged in RIPK1K45A mice. Inhibition of IDO with EPA was protective in TLCS-AP. Both Nec-1 and RIPK1K45A modification inhibited TLCS- and FAEE-induced PAC necrosis in vitro. Nec-1 did not affect TLCS-induced Ca2+ entry in PACs, however, it inhibited an associated ROS elevation. The results demonstrate protective actions of Nec-1 in multiple models. However, RIPK1-dependent necroptosis only partially contributed to beneficial effects, and actions on targets such as IDO are likely to be important.
Keywords: acute pancreatitis; receptor-interacting protein kinase 1; RIPK1; necrostatin-1; necroptosis; cell death; indoleamine 2,3-dioxygenase; epacadostat acute pancreatitis; receptor-interacting protein kinase 1; RIPK1; necrostatin-1; necroptosis; cell death; indoleamine 2,3-dioxygenase; epacadostat

Share and Cite

MDPI and ACS Style

Ouyang, Y.; Wen, L.; Armstrong, J.A.; Chvanov, M.; Latawiec, D.; Cai, W.; Awais, M.; Mukherjee, R.; Huang, W.; Gough, P.J.; et al. Protective Effects of Necrostatin-1 in Acute Pancreatitis: Partial Involvement of Receptor Interacting Protein Kinase 1. Cells 2021, 10, 1035. https://doi.org/10.3390/cells10051035

AMA Style

Ouyang Y, Wen L, Armstrong JA, Chvanov M, Latawiec D, Cai W, Awais M, Mukherjee R, Huang W, Gough PJ, et al. Protective Effects of Necrostatin-1 in Acute Pancreatitis: Partial Involvement of Receptor Interacting Protein Kinase 1. Cells. 2021; 10(5):1035. https://doi.org/10.3390/cells10051035

Chicago/Turabian Style

Ouyang, Yulin, Li Wen, Jane A. Armstrong, Michael Chvanov, Diane Latawiec, Wenhao Cai, Mohammad Awais, Rajarshi Mukherjee, Wei Huang, Peter J. Gough, and et al. 2021. "Protective Effects of Necrostatin-1 in Acute Pancreatitis: Partial Involvement of Receptor Interacting Protein Kinase 1" Cells 10, no. 5: 1035. https://doi.org/10.3390/cells10051035

APA Style

Ouyang, Y., Wen, L., Armstrong, J. A., Chvanov, M., Latawiec, D., Cai, W., Awais, M., Mukherjee, R., Huang, W., Gough, P. J., Bertin, J., Tepikin, A. V., Sutton, R., & Criddle, D. N. (2021). Protective Effects of Necrostatin-1 in Acute Pancreatitis: Partial Involvement of Receptor Interacting Protein Kinase 1. Cells, 10(5), 1035. https://doi.org/10.3390/cells10051035

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop