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Metabolic and structural remodeling of heart‐derived H9c2 cells by AMPK activation
Author(s) -
Dai Jiazhen Minnie,
Saeedi Ramesh,
Sharma Vijay,
Saran Varun,
Parsons Hannah,
Dyck Jason,
Allard Michael
Publication year - 2009
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.23.1_supplement.577.9
Subject(s) - ampk , medicine , protein kinase a , amp activated protein kinase , beta oxidation , endocrinology , muscle hypertrophy , glycolysis , chemistry , kinase , metabolism , biochemistry
AMP‐activated protein kinase (AMPK), a kinase involved in control of cellular metabolism, inhibits pathologic cardiac hypertrophy development but also plays a role in skeletal muscle adaptation to exercise. We tested the hypothesis that AMPK activation per se results in structural and metabolic remodeling of heart muscle cells characteristic of that seen in physiologic cardiac hypertrophy. Adenoviral‐mediated over expression of a constitutively active form of AMPK (CA‐AMPK) was used to increase AMPK activity in H9c2 cells, a cell line from embryonic rat heart ventricle. Then, indices of cellular hypertrophy and substrate use were measured 48 hrs later. AMPK activity was ~40‐50% higher in CA‐AMPK treated cells than in untreated cells. This was accompanied by a ~20‐25% increase in total protein content and phenylalanine incorporation without a measurable increase in atrial natriuretc peptide expression. CA‐AMPK stimulated fatty acid oxidation and glycolysis, but did not significantly alter glucose oxidation. Thus, AMPK activation causes structural and metabolic remodeling in heart muscle cells different from that seen in pathologic settings, indicating AMPK activation alone leads to a physiologic form of hypertrophy in heart muscle cells and may alter the reciprocal relationship between fatty acid and glucose utilization. This research project is funded by Canadian Institute of Health Research.