Abstract
Sustained elevation in cytosolic Ca2+ concentration ([Ca2+]C) is believed to induce premature trypsin activation and initiate acute pancreatitis. Among many triggering factors, ethanol abuse is the most prevalent in provoking acute pancreatitis but with unknown etiological mechanism. Here we show that elevated [Ca2+]C is directly responsible for inducing premature trypsin activation in the zymogen granules (ZGs) of pancreas acinar cells and is exacerbated by ethanol treatment. In vitro, a highly cooperative ion exchange mechanism has been found to regulate elevation in [Ca2+]C induced premature trypsin activation. The sustained rise in [Ca2+]C triggers K+ influx into the ZGs in exchange for the release of matrix bound-Ca2+ and -H+. Such K+/Ca2+ ion-exchange mechanism promotes the amplification of mobile-Ca2+ concentration in the ZGs ([Ca2+]G) while K+ replaces bound-H+ by K+/H+ ion-exchange to decrease the pH within ZGs (pHG). Increasing [Ca2+]G with concomitant lowering of pHG generate premature trypsin activation in ZGs. Hence, our data suggest that ethanol abuse provokes a sustained rise in [Ca2+]C by which K+ influx induced ion-exchange mechanism initiates premature trypsin activation in acinar ZGs during acute pancreatitis.
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Ding, Y., Chen, E., Yang, K., Chin, WC. (2008). The Role of Ion-Exchange on Trypsin Premature Activation in Zymogen Granules. In: Pollack, G.H., Chin, WC. (eds) Phase Transitions in Cell Biology. Springer, Dordrecht. https://doi.org/10.1007/978-1-4020-8651-9_4
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DOI: https://doi.org/10.1007/978-1-4020-8651-9_4
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