title: Clusterin and Pycr1 alterations associate with strain and model differences in susceptibility to experimental pancreatitis.
abstract: Acute pancreatitis has several underlying etiologies, and results in consequences ranging from mild to complex multi-organ failure. The wide range of pathology suggests a genetic predisposition for progression. We compared the susceptibility to acute pancreatitis in BALB/c and FVB/N mice, coupled with proteomic analysis, in order to identify potential protein associations with pancreatitis progression.
  
  
  METHODS
  Pancreatitis was induced in BALB/c and FVB/N mice by administration of cerulein or feeding a choline-deficient, ethionine-supplemented (CDE) diet. Histology and changes in serum amylase were examined. Proteome profiling in cerulein-treated mice was performed using 2-dimensional differential in gel electrophoresis (2D-DIGE) followed by mass spectrometry analysis and biochemical validation.
  
  
  RESULTS
  Male and female FVB/N mice manifested more severe cerulein-induced pancreatitis as compared with BALB/c mice, but both strains were similarly susceptible to CDE-induced pancreatitis. Few of the 2D-DIGE alterations were validated by immunoblotting. Clusterin was markedly up-regulated after cerulein-induced pancreatitis in FVB/N but less-so in BALB/c mice. Pyrroline-5-carboxylate reductase (Pycr1), an enzyme involved in proline biosynthesis, had higher basal levels in FVB/N male and female mouse pancreata compared with BALB/c pancreata, and was relatively more resistant to degradation in FVB/N pancreata. However, serum and pancreas tissue proline levels were similar in the two strains.
  
  
  CONCLUSIONS
  FVB/N is more susceptible than BALB/c mice to cerulein-induced but not CDE-induced pancreatitis. Most of the 2D-DIGE alterations in the two strains likely relate to posttranslational modifications rather than protein level differences. Clusterin levels increase dramatically in association with pancreatitis severity, while Pycr1 is higher in FVB/N versus BALB/c pancreata basally and after induction of pancreatitis. Changes in proline metabolism may represent a novel potential genetic modifier in the context of pancreatitis.
authors.affiliation: Research & Development, Protein and Cell Analysis, Thermo Fisher Scientific, Bangalore, India.
authors.forename: Sapna
authors.initials: S
authors.lastname: Iyer
authors.affiliation: Department of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Min-Jung
authors.initials: MJ
authors.lastname: Park
authors.affiliation: Department of Pathology, University of Michigan, Ann Arbor, MI, USA.
authors.forename: David
authors.initials: D
authors.lastname: Moons
authors.affiliation: Department of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Raymond
authors.initials: R
authors.lastname: Kwan
authors.affiliation: Applied Biomics, Freemont, CA, USA.
authors.forename: Jian
authors.initials: J
authors.lastname: Liao
authors.affiliation: Hepatology Unit and Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China. Electronic address: 18602062738@163.com.
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, MI, USA; Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA; VA Ann Arbor Healthcare System, Ann Arbor, MI, USA. Electronic address: mbishr@umich.edu.
authors.forename: M Bishr
authors.initials: MB
authors.lastname: Omary
mesh_terms: D000681:Amylases / Q000097:blood; D000818:Animals; D002108:Ceruletide / Q000737:chemistry; D002794:Choline / Q000737:chemistry; D051152:Clusterin / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D005001:Ethionine / Q000737:chemistry; D005260:Female; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010195:Pancreatitis / Q000235:genetics* / Q000378:metabolism; D011392:Proline / Q000737:chemistry; D011499:Protein Processing, Post-Translational; D020543:Proteome; D011762:Pyrroline Carboxylate Reductases / Q000235:genetics* / Q000378:metabolism; D013045:Species Specificity; D000097502:delta-1-Pyrroline-5-Carboxylate Reductase
chemical_list: D000681:Amylases; D002108:Ceruletide; D002794:Choline; D051152:Clusterin; D005001:Ethionine; D011392:Proline; D020543:Proteome; D011762:Pyrroline Carboxylate Reductases; D000097502:delta-1-Pyrroline-5-Carboxylate Reductase; C495243:Clu protein, mouse
keywords: Cerulein; Clusterin; Pancreas; Pancreatitis; Pycr1