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Mol. Cells 2007; 24(2): 224-231

Published online January 1, 1970

© The Korean Society for Molecular and Cellular Biology

Regulation of BAD Protein by PKA, PKCδ and Phosphatases in Adult Rat Cardiac Myocytes Subjected to Oxidative Stress

Danuta Cieslak and Antigone Lazou

Abstract

H2O2, as an example of oxidative stress, induces cardiac myocyte apoptosis. Bcl-2 family proteins are key regulators of the apoptotic response while their functions can be regulated by post-translational modifications including phosphorylation, dimerization or proteolytic cleavage. In this study, we examined the role of various protein kinases in regulating total BAD protein levels in adult rat cardiac myocytes undergoing apoptosis. Stimulation with 0.1 mM H2O2, which induces apoptosis, resulted in a marked down-regulation of BAD protein, which is attributed to cleavage by caspases since it can be restored in the presence of a general caspase inhibitor. Inhibition of PKC, p38-MAPK, ERK1/2 and PI-3-K did not influence the reduced BAD protein levels observed after stimulation with H2O2. On the contrary, inhibition of PKA or specifically PKCδ resulted in up-regulation of BAD. Decreased caspase 3 activity was observed in H2O2 treated cells after inhibition of PKA or PKCδ whereas inhibition of PKA also resulted in improved cell survival. Furthermore, addition of okadaic acid to inhibit selected phosphatases resulted in enhanced BAD cleavage. These data suggest that, during oxidative stress-induced cardiac myocyte apoptosis, there is a caspase-dependent down-regulation of BAD protein, which seems to be regulated by coordinated action of PKA, PKCδ and phosphatases.

Keywords Apoptosis; BAD; Cardiac Myocyte; H2O2; Phosphatase; Protein Kinase

Article

Research Article

Mol. Cells 2007; 24(2): 224-231

Published online October 31, 2007

Copyright © The Korean Society for Molecular and Cellular Biology.

Regulation of BAD Protein by PKA, PKCδ and Phosphatases in Adult Rat Cardiac Myocytes Subjected to Oxidative Stress

Danuta Cieslak and Antigone Lazou

Abstract

H2O2, as an example of oxidative stress, induces cardiac myocyte apoptosis. Bcl-2 family proteins are key regulators of the apoptotic response while their functions can be regulated by post-translational modifications including phosphorylation, dimerization or proteolytic cleavage. In this study, we examined the role of various protein kinases in regulating total BAD protein levels in adult rat cardiac myocytes undergoing apoptosis. Stimulation with 0.1 mM H2O2, which induces apoptosis, resulted in a marked down-regulation of BAD protein, which is attributed to cleavage by caspases since it can be restored in the presence of a general caspase inhibitor. Inhibition of PKC, p38-MAPK, ERK1/2 and PI-3-K did not influence the reduced BAD protein levels observed after stimulation with H2O2. On the contrary, inhibition of PKA or specifically PKCδ resulted in up-regulation of BAD. Decreased caspase 3 activity was observed in H2O2 treated cells after inhibition of PKA or PKCδ whereas inhibition of PKA also resulted in improved cell survival. Furthermore, addition of okadaic acid to inhibit selected phosphatases resulted in enhanced BAD cleavage. These data suggest that, during oxidative stress-induced cardiac myocyte apoptosis, there is a caspase-dependent down-regulation of BAD protein, which seems to be regulated by coordinated action of PKA, PKCδ and phosphatases.

Keywords: Apoptosis, BAD, Cardiac Myocyte, H2O2, Phosphatase, Protein Kinase

Mol. Cells
Jun 30, 2023 Vol.46 No.6, pp. 329~398
COVER PICTURE
The cellular proteostasis network is adaptively modulated upon cellular stress, thereby protecting cells from proteostasis collapse. Heat shock induces the translocation of misfolded proteins and the chaperone protein HSP70 into nucleolus, where nuclear protein quality control primarily occurs. Nuclear RNA export factor 1 (green), nucleolar protein fibrillarin (red), and nuclei (blue) were visualized in NIH3T3 cells under basal (left) and heat shock (right) conditions (Park et al., pp. 374-386).

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