CD36 protein influences myocardial Ca2+ homeostasis and phospholipid metabolism: Conduction anomalies in CD36-deficient mice during fasting

Terri A. Pietka, Matthew S. Sulkin, Ondrej Kuda, Wei Wang, Dequan Zhou, Kathryn A. Yamada, Kui Yang, Xiong Su, Richard W. Gross, Jeanne M. Nerbonne, Igor R. Efimov, Nada A. Abumrad

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

Sarcolemmal CD36 facilitates myocardial fatty acid (FA) uptake, which is markedly reduced in CD36-deficient rodents and humans. CD36 also mediates signal transduction events involving a number of cellular pathways. In taste cells and macrophages, CD36 signaling was recently shown to regulate store-responsive Ca2+ flux and activation of Ca2+-dependent phospholipases A2 that cycle polyunsaturated FA into phospholipids. It is unknown whether CD36 deficiency influences myocardial Ca2+ handling and phospholipid metabolism, which could compromise the heart, typically during stresses. Myocardial function was examined in fed or fasted (18-22 h) CD36 -/- and WT mice. Echocardiography and telemetry identified conduction anomalies that were associated with the incidence of sudden death in fasted CD36-/- mice. No anomalies or death occurred in WT mice during fasting. Optical imaging of perfused hearts from fasted CD36-/- mice documented prolongation of Ca2+ transients. Consistent with this, knockdown of CD36 in cardiomyocytes delayed clearance of cytosolic Ca 2+. Hearts of CD36-/- mice (fed or fasted) had 3-fold higher SERCA2a and 40% lower phospholamban levels. Phospholamban phosphorylation by protein kinase A (PKA) was enhanced after fasting reflecting increased PKA activity and cAMP levels in CD36-/- hearts. Abnormal Ca2+ homeostasis in the CD36-/- myocardium associated with increased lysophospholipid content and a higher proportion of 22:6 FA in phospholipids suggests altered phospholipase A2 activity and changes in membrane dynamics. The data support the role of CD36 in coordinating Ca2+ homeostasis and lipid metabolism and the importance of this role during myocardial adaptation to fasting. Potential relevance of the findings to CD36-deficient humans would need to be determined.

Original languageEnglish
Pages (from-to)38901-38912
Number of pages12
JournalJournal of Biological Chemistry
Volume287
Issue number46
DOIs
StatePublished - Nov 9 2012

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