Observation of colocalziation played central role in understanding of the cause-effect relatioships between zymogen activation and other early events in secretagogue-induced acute pancreatitis. CoLocalizer Pro software was used by Dr. Van Acker and colleagues from Tufts-New England Medical Center in Boston to show that inhibition of cathepsin B by pre-treatment with CA-074me prevents intrapancreatic zymogen activation and reduces organellar fragility but it does not alter the caerulein-induced co-localization phenomenon or sub-cellular F-actin redistribution or prevent caerulein-induced activation of NF-B, ERK 1/2, and JNK, or up-regulated expression of cyto-chemokines. The authors concluded (a) that the co-localization phenomenon, F-actin redistribution, activation of pro-inflammatory transcription factors, and up-regulated expression of cyto-chemokines are not the result of zymogen activation, and (b) that these early events in pancreatitis are not dependent upon cathepsin B activity. The paper appeared in in American Journal of Physiology (Gastrointestinal and Liver Physiology), an official journal of The American Physiological Society ((2007) 292 G1738-G1746).
Monday, June 18, 2007
Colocalization of zymogens with lysosomal hydrolases
Observation of colocalziation played central role in understanding of the cause-effect relatioships between zymogen activation and other early events in secretagogue-induced acute pancreatitis. CoLocalizer Pro software was used by Dr. Van Acker and colleagues from Tufts-New England Medical Center in Boston to show that inhibition of cathepsin B by pre-treatment with CA-074me prevents intrapancreatic zymogen activation and reduces organellar fragility but it does not alter the caerulein-induced co-localization phenomenon or sub-cellular F-actin redistribution or prevent caerulein-induced activation of NF-B, ERK 1/2, and JNK, or up-regulated expression of cyto-chemokines. The authors concluded (a) that the co-localization phenomenon, F-actin redistribution, activation of pro-inflammatory transcription factors, and up-regulated expression of cyto-chemokines are not the result of zymogen activation, and (b) that these early events in pancreatitis are not dependent upon cathepsin B activity. The paper appeared in in American Journal of Physiology (Gastrointestinal and Liver Physiology), an official journal of The American Physiological Society ((2007) 292 G1738-G1746).
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