PMID- 25370603
OWN - NLM
STAT- MEDLINE
DCOM- 20150410
LR  - 20220129
IS  - 1470-8728 (Electronic)
IS  - 0264-6021 (Print)
IS  - 0264-6021 (Linking)
VI  - 465
IP  - 3
DP  - 2015 Feb 1
TI  - The role of Ca2+ influx in endocytic vacuole formation in pancreatic acinar 
      cells.
PG  - 405-12
LID - 10.1042/BJ20140398 [doi]
AB  - The inducers of acute pancreatitis trigger a prolonged increase in the cytosolic 
      Ca(2+) concentration ([Ca(2+)]c), which is responsible for the damage to and 
      eventual death of pancreatic acinar cells. Vacuolization is an important 
      indicator of pancreatic acinar cell damage. Furthermore, activation of 
      trypsinogen occurs in the endocytic vacuoles; therefore the vacuoles can be 
      considered as 'initiating' organelles in the development of the cell injury. In 
      the present study, we investigated the relationship between the formation of 
      endocytic vacuoles and Ca(2+) influx developed in response to the inducers of 
      acute pancreatitis [bile acid taurolithocholic acid 3-sulfate (TLC-S) and 
      supramaximal concentration of cholecystokinin-8 (CCK)]. We found that the 
      inhibitor of STIM (stromal interaction molecule)/Orai channels, GSK-7975A, 
      effectively suppressed both the Ca(2+) influx (stimulated by inducers of 
      pancreatitis) and the formation of endocytic vacuoles. Cell death induced by 
      TLC-S or CCK was also inhibited by GSK-7975A. We documented the formation of 
      endocytic vacuoles in response to store-operated Ca(2+) entry (SOCE) induced by 
      thapsigargin [TG; inhibitor of sarcoplasmic/endoplasmic reticulum (ER) Ca(2+) 
      pumps] and observed strong inhibition of TG-induced vacuole formation by 
      GSK-7975A. Finally, we found that structurally-unrelated inhibitors of calpain 
      suppress formation of endocytic vacuoles, suggesting that this Ca2+-dependent 
      protease is a mediator between Ca(2+) elevation and endocytic vacuole formation.
FAU - Voronina, Svetlana
AU  - Voronina S
AD  - *Department of Cellular and Molecular Physiology, University of Liverpool, Crown 
      Street, Liverpool L69 3BX, U.K.
FAU - Collier, David
AU  - Collier D
AD  - *Department of Cellular and Molecular Physiology, University of Liverpool, Crown 
      Street, Liverpool L69 3BX, U.K.
FAU - Chvanov, Michael
AU  - Chvanov M
AD  - *Department of Cellular and Molecular Physiology, University of Liverpool, Crown 
      Street, Liverpool L69 3BX, U.K.
FAU - Middlehurst, Ben
AU  - Middlehurst B
AD  - *Department of Cellular and Molecular Physiology, University of Liverpool, Crown 
      Street, Liverpool L69 3BX, U.K.
FAU - Beckett, Alison J
AU  - Beckett AJ
AD  - *Department of Cellular and Molecular Physiology, University of Liverpool, Crown 
      Street, Liverpool L69 3BX, U.K.
FAU - Prior, Ian A
AU  - Prior IA
AD  - *Department of Cellular and Molecular Physiology, University of Liverpool, Crown 
      Street, Liverpool L69 3BX, U.K.
FAU - Criddle, David N
AU  - Criddle DN
AD  - *Department of Cellular and Molecular Physiology, University of Liverpool, Crown 
      Street, Liverpool L69 3BX, U.K.
FAU - Begg, Malcolm
AU  - Begg M
AD  - double daggerRespiratory Therapy Area Unit, Medicines Research Centre, GlaxoSmithKline, 
      Stevenage SG1 2NY, England, U.K.
FAU - Mikoshiba, Katsuhiko
AU  - Mikoshiba K
AD  - daggerLaboratory for Developmental Neurobiology, Riken Brain Science Institute, 2-1 
      Hirosawa, Wako City, Saitama 351-0198, Japan.
FAU - Sutton, Robert
AU  - Sutton R
AD  -  section signNIHR Liverpool Pancreas Biomedical Research Unit, University of Liverpool, Crown 
      Street, Liverpool L69 3BX, U.K.
FAU - Tepikin, Alexei V
AU  - Tepikin AV
AD  - *Department of Cellular and Molecular Physiology, University of Liverpool, Crown 
      Street, Liverpool L69 3BX, U.K.
LA  - eng
GR  - MR/K012967/1/MRC_/Medical Research Council/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Biochem J
JT  - The Biochemical journal
JID - 2984726R
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Acinar Cells/*metabolism
MH  - Animals
MH  - Calcium/*metabolism
MH  - Cells, Cultured
MH  - Mice
MH  - Pancreas/*cytology/*metabolism
MH  - Transport Vesicles/*metabolism
MH  - Vacuoles/*metabolism
PMC - PMC4303308
EDAT- 2014/11/06 06:00
MHDA- 2015/04/11 06:00
PMCR- 2015/01/22
CRDT- 2014/11/06 06:00
PHST- 2014/11/06 06:00 [entrez]
PHST- 2014/11/06 06:00 [pubmed]
PHST- 2015/04/11 06:00 [medline]
PHST- 2015/01/22 00:00 [pmc-release]
AID - BJ20140398 [pii]
AID - 10.1042/BJ20140398 [doi]
PST - ppublish
SO  - Biochem J. 2015 Feb 1;465(3):405-12. doi: 10.1042/BJ20140398.