Figure 1610

Protein processing in the endoplasmic reticu-lum (ER). To recover from serious injury, cells must synthesize and assemble new membrane (tight junction proteins) and secreted (growth factors) proteins. The ER is the initial site of synthesis of all membrane and secreted proteins. As a protein is translocated into the lumen of the ER it begins to interact with a group of resident ER proteins called molecular chaperones [20, 54-57]. Molecular chaperones bind transiently to and interact with these nascent polypeptides as they fold, assemble, and oligomerize [20, 54, 58]. Upon successful completion of folding or assembly, the molecular chaperones and the secretion-competent protein part company via a reaction that requires ATP hydrolysis, and the chaperones are ready for another round of protein folding [20, 59-61]. If a protein is recognized as being misfolded or misassem-bled it is retained within the ER via stable association with the molecular chaperones and is ultimately targeted for degradation [62]. Interestingly, some of the more characteristic features of epithelial ischemia include loss of cellular functions mediated by proteins that are folded and assembled in the ER (ie, cell adhesion molecules, integrins, tight junctional proteins, transporters). This suggests that proper functioning of the protein-folding machinery of the ER could be critically important to the ability of epithelial cells to withstand and recover from ischemic insult. ADP—adenosine diphosphate.

45' Ischemia

15' Ischemia

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