Activation of PKCβII is associated with the response to ischemia/reperfusion (I/R), though its role, either pathogenic or protective, has not been determined. In a murine model of single-lung I/R, evidence linking PKCβ to maladaptive responses is shown in the following studies. Homozygous PKCβ-null mice and WT mice fed the PKCβ inhibitor ruboxistaurin subjected to I/R displayed increased survival compared with controls. In PKCβ-null mice, phosphorylation of extracellular signal–regulated protein kinase-1 and -2 (ERK1/2), JNK, and p38 MAPK was suppressed in I/R. Expression of the immediate early gene, early growth response-1 (Egr-1), and its downstream target genes was significantly increased in WT mice in I/R, particularly in mononuclear phagocytes (MPs), whereas this expression was attenuated in PKCβ-null mice or WT mice fed ruboxistaurin. In vitro, hypoxia/reoxygenation-mediated induction of Egr-1 in MPs was suppressed by inhibition of PKCβ, ERK1/2, and JNK, but not by inhibition of p38 MAPK. These findings elucidate key roles for PKCβII activation in I/R by coordinated activation of MAPKs (ERK1/2, JNK) and Egr-1.
Tomoyuki Fujita, Tomohiro Asai, Martin Andrassy, David M. Stern, David J. Pinsky, Yu Shan Zou, Morihito Okada, Yoshifumi Naka, Ann Marie Schmidt, Shi-Fang Yan
Mark W. Musch, Lane L. Clarke, Daniel Mamah, Lara R. Gawenis, Zheng Zhang, William Ellsworth, David Shalowitz, Navdha Mittal, Petros Efthimiou, Ziad Alnadjim, Steve D. Hurst, Eugene B. Chang, Terrence A. Barrett
Gaël Nicolas, Caroline Chauvet, Lydie Viatte, Jean Louis Danan, Xavier Bigard, Isabelle Devaux, Carole Beaumont, Axel Kahn, Sophie Vaulont
Ganesan Ramesh, W. Brian Reeves
No posts were found with this tag.