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Activation Of PKC Isoforms In Hypertrophied GLUT4 Deficient Hearts Thunder Jalili, Claudia Guzman, Huifeng Jin, E. Dale Abel
Author(s) -
Jalili Thunder,
Guzman Claudia,
Jin Huifeng,
Abel E. Dale
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a741-b
Subject(s) - medicine , protein kinase c , cytosol , endocrinology , oxidative stress , glutathione , muscle hypertrophy , glut4 , chromosomal translocation , chemistry , biology , kinase , biochemistry , glucose transporter , enzyme , gene , insulin
Cardiac specific deletion of the GLUT4 glucose transporter (G4H−/−) leads to compensated cardiac hypertrophy. The mechanisms responsible for this phenotype are unknown, but may be related to oxidative stress‐mediated Protein kinase C (PKC) activation. We hypothesized that PKCα, β, δ, and ε activation, previously implicated in cardiac hypertrophy and failure, is present in G4H−/− hearts. Immunoblotting of total and phosphorylated (p) PKC from cytosolic and membrane cardiac fractions was done on 40–60 week old female G4H−/− mice (n=5) and non‐transgenic (NTG) littermates (n=5). PKC activation was determined by calculating a translocation index of membrane:cytosol of G4H−/− normalized to NTG. Cardiac hypertrophy was present in G4H−/− mice (heart:tibia length, G4H−/− 9.24±0.70 vs. NTG 6.64±0.31, p=0.01). Translocation index of PKCα, βI, βII and δ in G4H−/− hearts was 20% (p=0.01), 116% (p=0.01), 93% (p=0.01) and 109% (p=0.001) greater, respectively, than NTG. PKCε was unchanged. Cytosolic and membrane levels of p‐PKCα/βII were 42% (p=0.01) and 55% (p<0.001) greater, respectively, than NTG while translocation of p‐PKCδ was 115% (p=0.01) greater. To determine if cardiac oxidative stress is associated with PKC activation, concentrations of reduced (GSH) and oxidized glutathione (GSSG) were measured. GSH was similar in NTG and G4H−/− hearts, but GSSG was greater. Thus decreased GSH:GSSG in G4H−/− suggests increased oxidative stress. We conclude that activation of these PKC isoforms may contribute to cardiac hypertrophy in the GLUT4 deficient heart, possibly through an oxidative stress mechanism induced by metabolic changes that develop as a consequence of cardiac GLUT4 deletion.