PERSPECTIVES IN PHARMACOLOGY The Role of Protein Kinase C Isoforms in Modulating Injury and Repair of the Intestinal Barrier
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چکیده
Gastrointestinal cells express a diverse group of protein kinase C (PKC) isoforms that play critical roles in a number of cell functions, including intracellular signaling and barrier integrity. PKC isoforms expressed by gastrointestinal epithelial cells consist of three major PKC subfamilies: conventional isoforms ( , 1, 2, and ), novel isoforms ( , , , , and ), and atypical isoforms ( , , and ). This review highlights recent discoveries, including our own, that some PKC isoforms in gastrointestinal epithelia monolayer cell culture are involved in injury to, whereas others are involved in protection of, intestinal barrier integrity. For example, certain PKC isoforms aggravate oxidative damage, whereas others protect against it. These findings suggest that the development of agents that selectively activate or inhibit specific PKC isoforms may lead to new therapeutic modalities for important gastrointestinal disorders such as cancer and inflammatory bowel disease. This review focuses on protein kinase C (PKC) isoforms expressed in epithelial cells of the gastrointestinal tract, especially the intestine. PKC isoforms are involved in signal transduction in several vital intracellular pathways, including cell proliferation, differentiation, apoptosis, adhesion, membrane remodeling, migration, ion secretion, and barrier function. Excellent reviews have addressed PKC isoforms individually, but not as a group; nor has it been shown that specific PKC isoforms can be involved in damage, whereas others are involved in the protection of the same cells. The PKC isoforms expressed in intestinal tissue include at least 12 known isoenzymes that differ in their mechanism of activation, tissue expression, intracellular distribution, and substrate specificity. This suggests that each isoenzyme may have a unique role in signaling and cell function.
منابع مشابه
The role of protein kinase C isoforms in modulating injury and repair of the intestinal barrier.
Gastrointestinal cells express a diverse group of protein kinase C (PKC) isoforms that play critical roles in a number of cell functions, including intracellular signaling and barrier integrity. PKC isoforms expressed by gastrointestinal epithelial cells consist of three major PKC subfamilies: conventional isoforms (alpha, beta1, beta2, and gamma), novel isoforms (delta, epsilon, theta, eta, an...
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تاریخ انتشار 2005