![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
Vol. 301, Issue 3, 852-866, June 2002
1 Isoform of Protein Kinase C Mediates the Protective
Effects of Epidermal Growth Factor on the Dynamic Assembly of F-Actin
Cytoskeleton and Normalization of Calcium Homeostasis in Human Colonic
Cells
Departments of Internal Medicine (Section of Gastroenterology and
Nutrition), Pharmacology, and Molecular Physiology, Rush University
Medical Center, Chicago, Illinois (A.B., J.Z.F., A.F., L.Z., A.K.); and
Institute of Human Nutrition, Columbia University, New York, New York
(D.A.T.)
Using intestinal monolayers, we showed that F-actin cytoskeletal
stabilization and Ca2+ normalization contribute to
epidermal growth factor (EGF)-mediated protection against oxidant
injury. However, the intracellular mediator responsible for these
protective effects remains unknown. Since the protein kinase C-
1
(PKC-1) isoform is abundant in our naive (N) cells, we hypothesized
that PKC-1 is essential to EGF protection. Monolayers of N Caco-2
cells were exposed to H2O2 ± EGF, PKC, or
Ca2+ modulators. Other cells were transfected to
over-express PKC-1 or to inhibit its expression and then pretreated
with low or high doses of EGF or a PKC activator, OAG
(1-oleoyl-2-acetyl-sn-glycerol), before H2O2.
In N monolayers exposed to oxidant, pretreatment with EGF or PKC
activators activated PKC-1, enhanced 45Ca2+
efflux, normalized Ca2+, decreased monomeric G-actin,
increased stable F-actin, and protected the cytoarchitecture of the
actin. PKC inhibitors prevented these protective effects. Transfected
cells stably over-expressing PKC-1 (+3.1-fold) but not N cell
monolayers were protected from injury by even lower doses of EGF or
OAG. EGF or OAG rapidly activated the over-expressed PKC-1.
Antisense inhibition of PKC-1 expression (
90%) prevented all
measures of EGF protection. Inhibitors of Ca2+-ATPase
prevented EGF protection in N cells as well as protective synergism in
transfected cells. EGF protects the assembly of the F-actin
cytoskeleton in intestinal monolayers against oxidants in large part
through the activation of PKC-1. EGF normalizes Ca2+ by
enhancing Ca2+ efflux through PKC-1. We have identified
novel biologic functions, protection of actin and Ca2+
homeostasis, among the classical isoforms of PKC.
This article has been cited by other articles:
|
|
 |
|
  C. B. Forsyth, A. Banan, A. Farhadi, J. Z. Fields, Y. Tang, M. Shaikh, L. J. Zhang, P. A. Engen, and A. Keshavarzian Regulation of Oxidant-Induced Intestinal Permeability by Metalloprotease-Dependent Epidermal Growth Factor Receptor Signaling J. Pharmacol. Exp. Ther., April 1, 2007; 321(1): 84 - 97. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Farhadi, A. Keshavarzian, Z. Ranjbaran, J. Z. Fields, and A. Banan The Role of Protein Kinase C Isoforms in Modulating Injury and Repair of the Intestinal Barrier J. Pharmacol. Exp. Ther., January 1, 2006; 316(1): 1 - 7. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. Fleegal, S. Hom, L. K. Borg, and T. P. Davis Activation of PKC modulates blood-brain barrier endothelial cell permeability changes induced by hypoxia and posthypoxic reoxygenation Am J Physiol Heart Circ Physiol, November 1, 2005; 289(5): H2012 - H2019. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Vilella, E. Herrero, J. Torres, and M. A. de la Torre-Ruiz Pkc1 and the Upstream Elements of the Cell Integrity Pathway in Saccharomyces cerevisiae, Rom2 and Mtl1, Are Required for Cellular Responses to Oxidative Stress J. Biol. Chem., March 11, 2005; 280(10): 9149 - 9159. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Banan, L. J. Zhang, M. Shaikh, J. Z. Fields, A. Farhadi, and A. Keshavarzian Key role of PLC-{gamma} in EGF protection of epithelial barrier against iNOS upregulation and F-actin nitration and disassembly Am J Physiol Cell Physiol, October 1, 2003; 285(4): C977 - C993. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. J. Kelly, Y. Zhang, C. Hepper, R. M. Gow, K. Jaworski, B. E. Kemp, J. L. Wilkinson-Berka, and R. E. Gilbert Protein Kinase C {beta} Inhibition Attenuates the Progression of Experimental Diabetic Nephropathy in the Presence of Continued Hypertension Diabetes, February 1, 2003; 52(2): 512 - 518. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Banan, L. Zhang, J. Z. Fields, A. Farhadi, D. A. Talmage, and A. Keshavarzian PKC-zeta prevents oxidant-induced iNOS upregulation and protects the microtubules and gut barrier integrity Am J Physiol Gastrointest Liver Physiol, October 1, 2002; 283(4): G909 - G922. [Abstract] [Full Text] [PDF]
|
|
 |
 |
 |
|
 |
 |
 |
