Acute Pancreatitis: A Multifaceted Set of Organelle and Cellular Interactions

Figure 1 presents a summary of this article in showing environmental stressors and genetic factors known to increase the risk for pancreatitis. As pointed out earlier, some risk factors act in combination to promote the disease as exemplified to alcohol abuse and smoking; and it is likely that genetic alterations also can increase susceptibility when combined with a lifestyle factor such as alcohol abuse.37Whitcomb D.C. LaRusch J. Krasinskas A.M. et al.Common genetic variants in the CLDN2 and PRSS1-PRSS2 loci alter risk for alcohol-related and sporadic pancreatitis.Nat Genet. 2012; 44: 1349-1354Crossref PubMed Scopus (232) Google Scholar Although not completely explored, stressors such as gallstones and the effect their passage has on reflux of bile acids into the pancreas could act through increased calcium influx to cause mitochondrial de-energinization.89Kim J.Y. Kim K.H. Lee J.A. et al.Transporter-mediated bile acid uptake causes Ca2+-dependent cell death in rat pancreatic acinar cells.Gastroenterology. 2002; 122: 1941-1953Abstract Full Text Full Text PDF PubMed Scopus (141) Google Scholar, 90Kim M.S. Hong J.H. Li Q. et al.Deletion of TRPC3 in mice reduces store-operated Ca2+ influx and the severity of acute pancreatitis.Gastroenterology. 2009; 137: 1509-1517Abstract Full Text Full Text PDF PubMed Scopus (121) Google Scholar, 91Petersen O.H. Sutton R. Ca2+ signalling and pancreatitis: effects of alcohol, bile and coffee.Trends Pharmacol Sci. 2006; 27: 113-120Abstract Full Text Full Text PDF PubMed Scopus (127) Google ScholarFigure 1Summary of environmental stressors and genetic factors known to increase the risk for pancreatitis. CFTR, cystic fibrosis transmembrane conductance regulator; TFs, transcription factors.View Large Image Figure ViewerDownload Hi-res image Download (PPT)