RESUMEN
Acute pancreatitis is an inflammatory disease with no specific treatment. One of the main reasons behind the lack of specific therapy is that the pathogenesis of acute pancreatitis is poorly understood. During the development of acute pancreatitis, the disease-inducing factors can damage both cell types of the exocrine pancreas, namely the acinar and ductal cells. Because damage of either of the cell types can contribute to the inflammation, it is crucial to find common intracellular mechanisms that can be targeted by pharmacological therapies. Despite the many differences, recent studies revealed that the most common factors that induce pancreatitis cause mitochondrial damage with the consequent breakdown of bioenergetics, that is, ATP depletion in both cell types. In this review, we summarize our knowledge of mitochondrial function and damage within both pancreatic acinar and ductal cells. We also suggest that colloidal ATP delivery systems for pancreatic energy supply may be able to protect acinar and ductal cells from cellular damage in the early phase of the disease. An effective energy delivery system combined with the prevention of further mitochondrial damage may, for the first time, open up the possibility of pharmacological therapy for acute pancreatitis, leading to reduced disease severity and mortality.
Asunto(s)
Mitocondrias/patología , Pancreatitis/metabolismo , Pancreatitis/patología , Pancreatitis/fisiopatología , Animales , Humanos , Mitocondrias/metabolismoRESUMEN
In the board game 'Snakes and Ladders', placed on the image of a pancreatic acinar cell, calcium ions have to move from release sites in the secretory region to the nucleus. There is another important contraflow - from calcium entry channels in the basal part of the cell to ER (endoplasmic reticulum) terminals in the secretory granule region. Both transport routes are perilous as the messenger can disappear in any place on the game board. It can be grabbed by calcium ATPases of the ER (masquerading as a snake but functioning like a ladder) and tunnelled through its low buffering environment, it can be lured into the whirlpools of mitochondria uniporters and forced to regulate the tricarboxylic acid cycle, and it can be permanently placed inside the matrix of secretory granules and released only outside the cell. The organelles could trade calcium (e.g. from the ER to mitochondria and vice versa) almost depriving this ion the light of the cytosol and noble company of cytosolic calcium buffers. Altogether it is a rich and colourful story.
Asunto(s)
Señalización del Calcio/fisiología , Proteínas de Unión al Calcio/química , Proteínas de Unión al Calcio/fisiología , Animales , Transporte Biológico Activo , Humanos , Páncreas/química , Páncreas/citología , Páncreas/fisiologíaRESUMEN
Calcium is a ubiquitous signalling molecule, known to control a vast array of cellular processes. In order to retain stimulus fidelity, the cell encodes the increases in intracellular calcium in the form of oscillations that are regulated both temporally and spatially. Here, we review recent work, using the pancreatic acinar cell as a model system, on the mechanisms employed to generate and modulate cytosolic Ca(2+) signals, and the technical advances that have made these studies possible.