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LKB1/AMPK Signaling in the Diaphragm
Author(s) -
Brown Jacob Daniel,
Mongillo Anthony D.,
DiGiovanni Ryan A.,
Lane Matt D.,
Winder William W.,
Thomson David M.
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.955.7
Subject(s) - ampk , phosphorylation , amp activated protein kinase , medicine , endocrinology , protein kinase a , chemistry , skeletal muscle , acetyl coa carboxylase , microbiology and biotechnology , biology , pyruvate carboxylase , biochemistry , enzyme
The LKB1/AMP‐Activated Protein Kinase (AMPK) signaling pathway is a major regulator of skeletal muscle metabolic processes. During exercise, LKB1‐mediated phosphorylation of AMPK leads to its activation, promoting mitochondrial biogenesis and glucose transport, among other effects. The roles of LKB1 and AMPK have not been characterized in the diaphragm. Two methods of AMPK activation were used to characterize LKB1/AMPK signaling in diaphragms from muscle‐specific LKB1 knockout (KO) and littermate control (C) mice: (1) acute injection of 5‐aminoimidazole‐4‐carboxamide ribonucleoside (AICAR) and (2) 5‐min direct electrical stimulation (ES) of the diaphragm. Diaphragms were excised 60 minutes post‐AICAR injection and immediately after ES. AMPK phosphorylation increased with AICAR and ES in C but not KO mice. Acetyl CoA Carboxylase (ACC) phosphorylation increased with AICAR in C but not KO mice, but increased in both genotypes with ES. No differences in Hexokinase 2 (HK2) levels were evident. CREB phosphorylation was lower in KO diaphragms. While Cytochrome C (Cyto C) levels were lower in KO diaphragms, Uncoupling Protein 3 (UCP‐3) levels were not different between genotypes. In conclusion, AMPK is activated in an LKB1‐dependent manner in the diaphragm by AICAR injection and direct ES. This study was supported by National Institute of Arthritis and Musculoskeletal and Skin Diseases Grant AR‐051928.