Format

Send to

Choose Destination
Am J Physiol Heart Circ Physiol. 2002 Jan;282(1):H320-7.

Protein kinase C-zeta modulates thromboxane A(2)-mediated apoptosis in adult ventricular myocytes via Akt.

Author information

1
Program in Cardiovascular Sciences, Section of Cardiology, Department of Medicine, University of Illinois at Chicago, M/C 787, 840 S. Wood St., Chicago, IL 60612, USA. shizukud@uic.edu

Abstract

We hypothesized that thromboxane A(2) (TxA(2)) receptor stimulation directly induces apoptosis in adult cardiac myocytes. To investigate this, we exposed cultured adult rat ventricular myocytes (ARVM) to a TxA(2) mimetic [1S-[1alpha,2alpha(Z),3beta(1E,3S*),4alpha]]-7-[3-[3-hydroxy-4-(4-iodophenoxy)-1-butenyl]-7-oxabicyclo[2.2.1]hept-2-yl]-5-heptenoic acid (I-BOP) for 24 h. Stimulation with I-BOP induced apoptosis in a dose-dependent manner and was completely prevented by a TxA(2) receptor antagonist, SQ-29548. We further investigated the role of protein kinase C (PKC) in this process. TxA(2) stimulation resulted in membrane translocation of PKC-zeta but not PKC-alpha, -betaII, -delta, and -epsilon at 3 min and 1 h. The activation of PKC-zeta by I-BOP was confirmed using an immune complex kinase assay. Treatment of ARVM with a cell-permeable PKC-zeta pseudosubstrate peptide (zeta-PS) significantly attenuated apoptosis by I-BOP. In addition, I-BOP treatment decreased baseline Akt activity and its decrease was reversed by treatment with zeta-PS. The inhibition of phosphatidylinositol 3-kinase upstream of Akt by wortmannin or LY-294002 abolished the antiapoptotic effect of zeta-PS. Therefore, our results suggest that the activation of PKC-zeta modulates TxA(2) receptor-mediated apoptosis at least, in part, through Akt activity in adult cardiac myocytes.

[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Atypon
Loading ...
Support Center