Language:

The serum protein renalase reduces injury in experimental pancreatitis

The Journal of biological chemistry, 2017-12, Vol.292 (51), p.21047-21059 [Peer Reviewed Journal]

2017 © 2017 ASBMB. Currently published by Elsevier Inc; originally published by American Society for Biochemistry and Molecular Biology. ;ISSN: 0021-9258 ;EISSN: 1083-351X ;DOI: 10.1074/jbc.M117.789776 ;PMID: 29042438

Full text available

Citations Cited by

Actions
1. Add to My Research
2. Remove from My Research
3. E-mail
4. Print
5. Permalink
6. Citation
7. EasyBib
8. EndNote
9. RefWorks
10. Delicious
11. Export RIS
12. Export BibTeX

Title:
The serum protein renalase reduces injury in experimental pancreatitis
Author: Kolodecik, Thomas R. ; Reed, Anamika M. ; Date, Kimie ; Shugrue, Christine A. ; Patel, Vikhil ; Chung, Shang-Lin ; Desir, Gary V. ; Gorelick, Fred S.
Subjects: Acinar Cells - drug effects ; Acinar Cells - metabolism ; Acinar Cells - pathology ; Animals ; Anti-Inflammatory Agents, Non-Steroidal - metabolism ; Anti-Inflammatory Agents, Non-Steroidal - therapeutic use ; Biomarkers - metabolism ; Calcium Signaling - drug effects ; Carbachol - pharmacology ; Cell Line ; cell signaling ; Ceruletide - toxicity ; chymotrypsin ; Enzyme Activation - drug effects ; Fluorescent Antibody Technique, Indirect ; Gene Expression Regulation, Enzymologic - drug effects ; Humans ; Hypertension - etiology ; Hypertension - prevention & control ; Ligands ; Membrane Transport Modulators - pharmacology ; Mice ; Mice, Knockout ; Molecular Bases of Disease ; Monoamine Oxidase - blood ; Monoamine Oxidase - genetics ; Monoamine Oxidase - metabolism ; Monoamine Oxidase - therapeutic use ; pancreas ; Pancreas - drug effects ; Pancreas - immunology ; Pancreas - metabolism ; Pancreas - pathology ; Pancreatitis - chemically induced ; Pancreatitis - drug therapy ; Pancreatitis - metabolism ; Pancreatitis - pathology ; plasma membrane calcium-transporting ATPase 4 (ATP2B4) ; Plasma Membrane Calcium-Transporting ATPases - antagonists & inhibitors ; Plasma Membrane Calcium-Transporting ATPases - chemistry ; Plasma Membrane Calcium-Transporting ATPases - genetics ; Plasma Membrane Calcium-Transporting ATPases - metabolism ; Recombinant Fusion Proteins - metabolism ; Recombinant Fusion Proteins - therapeutic use ; Taurolithocholic Acid - analogs & derivatives ; Taurolithocholic Acid - pharmacology ; trypsin
Is Part Of: The Journal of biological chemistry, 2017-12, Vol.292 (51), p.21047-21059
Description: Acute pancreatitis is a disease associated with inflammation and tissue damage. One protein that protects against acute injury, including ischemic injury to both the kidney and heart, is renalase, which is secreted into the blood by the kidney and other tissues. However, whether renalase reduces acute injury associated with pancreatitis is unknown. Here, we used both in vitro and in vivo murine models of acute pancreatitis to study renalase's effects on this condition. In isolated pancreatic lobules, pretreatment with recombinant human renalase (rRNLS) blocked zymogen activation caused by cerulein, carbachol, and a bile acid. Renalase also blocked cerulein-induced cell injury and histological changes. In the in vivo cerulein model of pancreatitis, genetic deletion of renalase resulted in more severe disease, and administering rRNLS to cerulein-exposed WT mice after pancreatitis onset was protective. Because pathological increases in acinar cell cytosolic calcium levels are central to the initiation of acute pancreatitis, we also investigated whether rRNLS could function through its binding protein, plasma membrane calcium ATPase 4b (PMCA4b), which excretes calcium from cells. We found that PMCA4b is expressed in both murine and human acinar cells and that a PMCA4b-selective inhibitor worsens pancreatitis-induced injury and blocks the protective effects of rRNLS. These findings suggest that renalase is a protective plasma protein that reduces acinar cell injury through a plasma membrane calcium ATPase. Because exogenous rRNLS reduces the severity of acute pancreatitis, it has potential as a therapeutic agent.
Publisher: United States: Elsevier Inc
Language: English
Identifier: ISSN: 0021-9258
EISSN: 1083-351X
DOI: 10.1074/jbc.M117.789776
PMID: 29042438
Source: MEDLINE
PubMed Central
Alma/SFX Local Collection

Back to results list


INSPIRE LIBRARY - TON DUC THANG UNIVERSITY	(84-028) 37 755 057	Feedback
19 Nguyen Huu Tho St. Dist.7, HCM	thuvien@tdtu.edu.vn	Feedback

The serum protein renalase reduces injury in experimental pancreatitis

2017 © 2017 ASBMB. Currently published by Elsevier Inc; originally published by American Society for Biochemistry and Molecular Biology. ;ISSN: 0021-9258 ;EISSN: 1083-351X ;DOI: 10.1074/jbc.M117.789776 ;PMID: 29042438

Searching Remote Databases, Please Wait