Proteomics as a Systems Approach to Pancreatitis

Abstract

Proteomics is an approach to looking at the identity, amount, proteolysis, compartmentalization and post-translational modification of a large number of proteins simultaneously in a cell or tissue. Recently, proteomics has begun to be applied to the study of pancreatitis to ascertain mechanisms of disease and search for biomarkers of disease. Most mechanistic work has been carried out in animal models of acute pancreatitis. In eight studies, 97 proteins have been reported to increase, 55 to decrease and 23 to undergo proteolysis. Proteins showing increases are most often related to stress, inflammation or the cytoskeleton while decreases are seen in digestive enzymes and proteins related to metabolism. Many protein changes however, are not consistent between studies and only the most recent studies are rigorous and quantitative. By contrast, biomarker studies have focused on pancreatic juice and plasma of humans with disease and often are directed at distinguishing chronic pancreatitis from cancer. Chronic pancreatitis has also been investigated in tissue sections of histological samples. In this review the results of studies to date are described as well as coverage of the methods used and special issues that must be considered. Areas are pointed out that are worthy of future study.

Mnk1 is a novel acinar cell-specific kinase required for exocrine pancreatic secretion and response to pancreatitis in mice

“…In agreement with proteomic studies assessing the effects of caerulein administration,33 we found reduced digestive enzymes using both western blotting and enzyme activity in WT mice. Mnk1 inactivation led to altered caerulein-associated downregulation of digestive enzymes and total protein content.…”

Molecular architecture of mouse and human pancreatic zymogen granules: protein components and their copy numbers

“… 2004 ; Paulo et al . 2013 ; Williams 2013 ). Our results represent the first effort to identify pancreatic ZG proteins from human pancreatic acini.…”

Clusterin and Pycr1 alterations associate with strain and model differences in susceptibility to experimental pancreatitis

“…For example, Apoa1 is involved in inflammation and increased during pancreatitis in rats [23]; serpinA3k is reported to have a protective function in pancreatitis since it is a proteinase inhibitor and thus important to limit the activity of proteinases that are released prematurely in the pancreatic tissue [24]; and Prdx6 is associated with elevated oxidative stress [25,26]. None of these three proteins showed significant difference in protein levels between the two strains.…”