Molecular and cellular mechanisms of pancreatic injury

Abstract

Purpose of review-This review focuses on studies from the past year that highlight molecular and cellular mechanisms of pancreatic injury arising from acute and chronic pancreatitis.Recent findings-Factors that induce or ameliorate injury as well as cellular pathways involved have been examined. Causative or sensitizing factors include refluxed bile acids, hypercalcemia, ethanol, hypertriglyceridemia, and acidosis. In addition, the diabetes drug exendin-4 has been associated with pancreatitis, whereas other drugs may reduce pancreatic injury. The intracellular events that influence disease severity are better understood. Cathepsin-L promotes injury through an antiapoptotic effect, rather than by trypsinogen activation. In addition, specific trypsinogen mutations lead to trypsinogen misfolding, endoplasmic reticulum stress, and injury. Endogenous trypsin inhibitors and upregulation of proteins including Bcl-2, fibroblast growth factor 21, and activated protein C can reduce injury. Immune cells, however, have been shown to increase injury via an antiapoptotic effect. Summary-The current findings are critical to understanding how causative factors initiate downstream cellular events resulting in pancreatic injury. Such knowledge will aid in the development of targeted treatments for pancreatitis. This review will first discuss factors influencing pancreatic injury, and then conclude with studies detailing the cellular mechanisms involved.

Toxicological effects of benzo(a)pyrene, DDT and their mixture on the green mussel Perna viridis revealed by proteomic and metabolomic approaches

“…SOD is a typical antioxidant enzyme and plays a critical role in ROS (reactive oxygen species) scavenging (Hern andez-Nistal et al, 2002;Kim et al, 2011). In mussel, oxidative stress is a prominent feature of DDT toxicity, seen from the increase of gelsolin and actin, it ultimately generate complex cytoskeletal rearrangements in gill cell (Riva et al, 2011;Thrower et al, 2010).…”

Induction of chronic pancreatitis by pancreatic duct ligation activates BMP2, apelin, and PTHrP expression in mice

“…Although utilization of experimental models has helped identify molecular mechanisms linked to development of CP (19,32,41,47), significant gaps persist in our knowledge of endogenous factors that function to either inhibit or amplify the inflammatory-fibrosis cascade (7,9,41), a key component of the CP disease process.…”

Endokrine Störungen und Verdauungstrakt

“…Wahrscheinlich ist die Hyperkalzämie per se und nicht der primäre Hyperparathyreodismus der Trigger für eine akute Pankreatitis, da auch Hyperkalzämien durch andere Ursachen (Malignome) zu einer Pankreatitis führen können [45,46]. Pathogenetisch werden entweder Kalziumablagerungen in den Azini mit nachfolgender Entzün-dung oder eine hyperkalzämiegetriggerte Aktivierung von Trypsinogen diskutiert [47,48].…”