English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Toxic alcohol effects on pancreatic acinar cells, causing the often fatal human disease acute pancreatitis, are principally mediated by fatty acid ethyl esters (non-oxidative products of alcohol and fatty acids), emptying internal stores of Ca2+ . This excessive Ca2+ liberation induces Ca2+ -dependent necrosis due to intracellular trypsin activation. Our aim was to identify the specific source of the Ca2+ release linked to the fatal intracellular protease activation. In 2-photon permeabilized mouse pancreatic acinar cells, we monitored changes in the Ca2+ concentration in the thapsigargin-sensitive endoplasmic reticulum (ER) as well as in a bafilomycin-sensitive acid compartment, localized exclusively in the apical granular pole. We also assessed trypsin activity in the apical granular region. Palmitoleic acid ethyl ester (POAEE) elicited Ca2+ release from both the ER as well as the acid pool, but trypsin activation depended predominantly on Ca2+ release from the acid pool, that was mainly mediated by functional inositol 1,4,5- trisphosphate receptors (IP3 Rs) of types 2 and 3. POAEE evoked very little Ca2+ release and trypsin activation when IP3 Rs of both types 2 and 3 were knocked out. Antibodies against IP3 Rs of types 2 and 3, but not type 1, markedly inhibited POAEE-elicited Ca2+ release and trypsin activation. We conclude that Ca2+ release through IP3 Rs of types 2 and 3 in the acid granular Ca2+ store induces intracellular protease activation, and propose that this is a critical process in the initiation of alcohol-related acute pancreatitis.

Pancreatic protease activation by alcohol metabolite depends on Ca 2+ release via acid store IP 3 receptors

Pancreatic protease activation by alcohol metabolite depends on Ca ²⁺ release via acid store IP ₃ receptors