Identification of epsilon PKC Targets During Cardiac Ischemic Injury

Author(s)

Budas, Grant ^[1] ; Costa, Jr., Helio Miranda ; Batista Ferreira, Julio Cesar ^[1] ; da Silva Ferreira, Andre Teixeira ^[2] ; Perales, Jonas ^[2] ; Krieger, Jose Eduardo ; Mochly-Rosen, Daria ^[1] ; Schechtman, Deborah ^[3]

Affiliation

^[1] Stanford Univ, Sch Med, Dept Chem & Syst Biol, Stanford, CA 94305 - USA

^[2] Inst Oswaldo Cruz, BR-20001 Rio De Janeiro - Brazil

^[3] Univ Sao Paulo, Inst Quim, Dept Bioquim, BR-05508000 Sao Paulo - Brazil

• Document type: Journal article
• Source: CIRCULATION JOURNAL; v. 76, n. 6, p. 1476-1485, JUN 2012.
• Web of Science Citations: 22

Abstract

Background: Epsilon-protein kinase C (epsilon PKC) protects the heart from ischemic injury. However, the mechanism(s) of epsilon PKC cardioprotection is still unclear. Identification of the epsilon PKC targets may aid in elucidating the epsilon PKC-mediated cardioprotective mechanisms. Previous studies, using epsilon PKC transgenic mice and difference in gel electrophoresis, identified proteins involved in glucose metabolism, the expression of which was modified by epsilon PKC. Those studies were accompanied by metabolomic analysis, suggesting that increased glucose oxidation may be responsible for the cardioprotective effect of epsilon PKC. Whether these epsilon PKC-mediated alterations were because of differences in protein expression or phosphorylation was not determined. Methods and Results: In the present study, we used an epsilon PKC -specific activator peptide, psi epsilon RACK, combined with phosphoproteomics, to find epsilon PKC targets, and identified that the proteins whose phosphorylation was altered by selective activation of epsilon PKC were mostly mitochondrial proteins. Analysis of the mitochondrial phosphoproteome led to the identification of 55 spots, corresponding to 37 individual proteins, exclusively phosphorylated, in the presence of psi epsilon RACK. The majority of the proteins identified were involved in glucose and lipid metabolism, components of the respiratory chain as well as mitochondrial heat shock proteins. Conclusions: The protective effect of epsilon PKC during ischemia involves phosphorylation of several mitochondrial proteins involved in glucose and lipid metabolism and oxidative phosphorylation. Regulation of these metabolic pathways by epsilon PKC phosphorylation may lead to epsilon PKC-mediated cardioprotection induced by psi epsilon RACK. (Circ J 2012; 76: 1476-1485) (AU)

• FAPESP's process: 05/54188-4 - Determination of protein kinase C role in differentiation and proliferation
• Grantee: Deborah Schechtman
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 09/03143-1 - Protein quality control in heart failure: role of different protein kinase C isozymes
• Grantee: Julio Cesar Batista Ferreira
• Support Opportunities: Scholarships in Brazil - Post-Doctoral