title: Liver kinase B1 inhibits the expression of inflammation-related genes postcontraction in skeletal muscle.
abstract: Skeletal muscle-specific liver kinase B1 (LKB1) knockout mice (skmLKB1-KO) exhibit elevated mitogen-activated protein kinase (MAPK) signaling after treadmill running. MAPK activation is also associated with inflammation-related signaling in skeletal muscle. Since exercise can induce muscle damage, and inflammation is a response triggered by damaged tissue, we therefore hypothesized that LKB1 plays an important role in dampening the inflammatory response to muscle contraction, and that this may be due in part to increased susceptibility to muscle damage with contractions in LKB1-deficient muscle. Here we studied the inflammatory response and muscle damage with in situ muscle contraction or downhill running. After in situ muscle contractions, the phosphorylation of both NF-κB and STAT3 was increased more in skmLKB1-KO vs. wild-type (WT) muscles. Analysis of gene expression via microarray and RT-PCR shows that expression of many inflammation-related genes increased after contraction only in skmLKB1-KO muscles. This was associated with mild skeletal muscle fiber membrane damage in skmLKB1-KO muscles. Gene markers of oxidative stress were also elevated in skmLKB1-KO muscles after contraction. Using the downhill running model, we observed significantly more muscle damage after running in skmLKB1-KO mice, and this was associated with greater phosphorylation of both Jnk and STAT3 and increased expression of SOCS3 and Fos. In conclusion, we have shown that the lack of LKB1 in skeletal muscle leads to an increased inflammatory state in skeletal muscle that is exacerbated by muscle contraction. Increased susceptibility of the muscle to damage may underlie part of this response.
authors.affiliation: Department of Physiology and Developmental Biology, Brigham Young University, Provo, Utah;
authors.forename: Ting
authors.initials: T
authors.lastname: Chen
authors.affiliation: Department of Physiology and Developmental Biology, Brigham Young University, Provo, Utah;
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Moore
authors.affiliation: Department of Biology, Brigham Young University, Provo, Utah.
authors.forename: Mark T W
authors.initials: MT
authors.lastname: Ebbert
authors.affiliation: Department of Physiology and Developmental Biology, Brigham Young University, Provo, Utah;
authors.forename: Natalie L
authors.initials: NL
authors.lastname: McVey
authors.affiliation: Department of Physiology and Developmental Biology, Brigham Young University, Provo, Utah;
authors.forename: Steven R
authors.initials: SR
authors.lastname: Madsen
authors.affiliation: Department of Physiology and Developmental Biology, Brigham Young University, Provo, Utah;
authors.forename: David M
authors.initials: DM
authors.lastname: Hallowell
authors.affiliation: Department of Physiology and Developmental Biology, Brigham Young University, Provo, Utah;
authors.forename: Alexander M
authors.initials: AM
authors.lastname: Harris
authors.affiliation: Department of Physiology and Developmental Biology, Brigham Young University, Provo, Utah;
authors.forename: Robin E
authors.initials: RE
authors.lastname: Char
authors.affiliation: Department of Physiology and Developmental Biology, Brigham Young University, Provo, Utah;
authors.forename: Ryan P
authors.initials: RP
authors.lastname: Mackay
authors.affiliation: Department of Nutrition, Dietetics and Food Science, Brigham Young University, Provo, Utah; and.
authors.forename: Chad R
authors.initials: CR
authors.lastname: Hancock
authors.affiliation: Department of Physiology and Developmental Biology, Brigham Young University, Provo, Utah;
authors.forename: Jason M
authors.initials: JM
authors.lastname: Hansen
authors.affiliation: Department of Biology, Brigham Young University, Provo, Utah.
authors.forename: John S
authors.initials: JS
authors.lastname: Kauwe
authors.affiliation: Department of Physiology and Developmental Biology, Brigham Young University, Provo, Utah; david_thomson@byu.edu.
authors.forename: David M
authors.initials: DM
authors.lastname: Thomson
mesh_terms: D055372:AMP-Activated Protein Kinases; D000818:Animals; D005080:Exercise Test / Q000379:methods; D005260:Female; D015870:Gene Expression / Q000235:genetics*; D007249:Inflammation / Q000235:genetics* / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D009119:Muscle Contraction / Q000235:genetics*; D018485:Muscle Fibers, Skeletal / Q000378:metabolism*; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress / Q000235:genetics; D010766:Phosphorylation / Q000235:genetics; D010805:Physical Conditioning, Animal / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D012420:Running / Q000502:physiology; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism
chemical_list: D016328:NF-kappa B; D050796:STAT3 Transcription Factor; D017346:Protein Serine-Threonine Kinases; C491654:Stk11 protein, mouse; D020928:Mitogen-Activated Protein Kinases; D055372:AMP-Activated Protein Kinases
keywords: AMPK; LKB1; downhill running; inflammation; oxidative stress