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The role of protein synthesis and digestive enzymes in acinar cell injury

Nature Reviews Gastroenterology & Hepatology volume 10, pages 362–370 (2013)Cite this article

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Abstract

The exocrine pancreas is the organ with the highest level of protein synthesis in the adult—each day the pancreas produces litres of fluid filled with enzymes that are capable of breaking down nearly all organic substances. For optimal health, the pancreas must produce sufficient enzymes of the right character to match the dietary intake. Disruption of normal pancreatic function occurs primarily as a result of dysfunction of the acinar cells that produce these digestive enzymes, and can lead to acute or chronic diseases. For many years, the prevailing dogma has been that inappropriate intracellular activation of the digestive enzymes produced by acinar cells was the key to pancreatic inflammatory diseases, as digestive enzymes themselves are potentially harmful to the cells that secrete them. However, we now know that many stressors can affect pancreatic acinar cells, and that these stressors can independently trigger pancreatic pathology through various mechanisms. This Review focuses on protein synthesis and active digestive enzymes—two key stressors faced by the acinar cell that are likely to be the major drivers of pathology encountered in the pancreas.

Key Points

  • The pancreas is a highly active organ, primarily because it contains the acinar cells that produce digestive enzymes

  • Physiological stresses on acinar cells include those associated with high levels of protein synthesis and with the production, storage and secretion of potentially damaging digestive enzymes

  • Synthesis of secreted proteins occurs in the endoplasmic reticulum (ER) and can be affected by many factors that result in protein misfolding or ER stress

  • Several compensatory mechanisms have evolved to protect the acinar cell from ER stress and inappropriate activation of digestive enzymes

  • Under normal circumstances, the compensatory mechanisms for ER stress and digestive enzyme activation are sufficient to fully protect the cells without any decrease in function

  • At high levels of stress, these same mechanisms result in acinar cell destruction and disease

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Figure 1: The components of the pancreas.
Figure 2: The structure of the pancreatic acinar cell.
Figure 3: ER stress responses that occur in pancreatic acinar cells.
Figure 4: Digestive enzyme stress responses in pancreatic acinar cells.

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Acknowledgements

C. D. Logsdon's scientific research is supported by grant DK052067 and AA020822.

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Authors and Affiliations

  1. The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Box 953, Houston, 77030, TX, USA

    Craig D. Logsdon

  2. Mayo Clinic, 200 First Street SW, Rochester, 55905, MN, USA

    Baoan Ji

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C. D. Logsdon researched the data for the article, and wrote the manuscript. C. D. Logsdon and B. Ji contributed to discussions of its content and undertook review and editing of the manuscript before submission.

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Correspondence to Craig D. Logsdon.

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Logsdon, C., Ji, B. The role of protein synthesis and digestive enzymes in acinar cell injury. Nat Rev Gastroenterol Hepatol 10, 362–370 (2013). https://doi.org/10.1038/nrgastro.2013.36

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