Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: KEGG:D02011 (
FAD
)
5,530
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
In the present study, we have employed confocal laser scanning microscopy to investigate the effect that stimulation of mouse pancreatic acinar cells with the secretagogue
cholecystokinin
(
CCK
) has on mitochondrial activity. We have monitored changes in cytosolic as well as mitochondrial Ca2+ concentrations, mitochondrial membrane potential and
FAD
autofluorescence by loading the cells with fluo-3, rhod-2 or JC-1, respectively. Our results show that stimulation of cells with
cholecystokinin
led to release of Ca2+ from intracellular stores that then accumulated into mitochondria. In the presence of the hormone a depolarization of mitochondrial membrane potential was observed, which partially recovered; in addition a transient increase in
FAD
autofluorescence could be observed. Similarly, treatment of cells with thapsigargin induced increases in mitochondrial Ca2+ and
FAD
autofluorescence, and depolarized mitochondria. Pretreament of cells with thapsigargin blocked
cholecystokinin
-evoked changes. Similar results were obtained when the cells were incubated in the presence of rotenone, which blocks the mitochondrial electron transport chain. Our findings are consistent with changes in mitochondrial activity in response to stimulation of pancreatic acinar cells with
cholecystokinin
. Following stimulation, mitochondria take up Ca2+ that could in turn activate the mitochondrial machinery that may match the energy supply necessary for the cell function during secretion, suggesting that Ca2+ can act as a regulator of mitochondrial activity.
...
PMID:Changes in mitochondrial activity evoked by cholecystokinin in isolated mouse pancreatic acinar cells. 1449 47
Acute pancreatitis is a frequent disease that lacks specific drug treatment. Unravelling the molecular mechanisms of acute pancreatitis is essential for the development of new therapeutics. Several inducers of acute pancreatitis trigger sustained Ca
2+
increases in the cytosol and mitochondria of pancreatic acinar cells. The mitochondrial calcium uniporter (MCU) mediates mitochondrial Ca
2+
uptake that regulates bioenergetics and plays an important role in cell survival, damage and death. Aberrant Ca
2+
signaling and mitochondrial damage in pancreatic acinar cells have been implicated in the initiation of acute pancreatitis. The primary aim of this study was to assess the involvement of the MCU in experimental acute pancreatitis. We found that pancreatic acinar cells from MCU
-/-
mice display dramatically reduced mitochondrial Ca
2+
uptake. This is consistent with the drastic changes of stimulus-metabolism coupling, manifested by the reduction of mitochondrial NADH/
FAD
+
responses to
cholecystokinin
and in the decrease of
cholecystokinin
-stimulated oxygen consumption. However, in three experimental models of acute pancreatitis (induced by caerulein, taurolithocholic acid 3-sulfate or palmitoleic acid plus ethanol), MCU knockout failed to reduce the biochemical and histological changes characterizing the severity of local and systemic damage. A possible explanation of this surprising finding is the redundancy of damaging mechanisms activated by the inducers of acute pancreatitis.
...
PMID:Knockout of the Mitochondrial Calcium Uniporter Strongly Suppresses Stimulus-Metabolism Coupling in Pancreatic Acinar Cells but Does Not Reduce Severity of Experimental Acute Pancreatitis. 3251 55
