Reduced rate of adenosine triphosphate synthesis by in vivo 31P nuclear magnetic resonance spectroscopy and downregulation of PGC-1beta in distal skeletal muscle following burn.
Using a mouse model of burn trauma, we tested the hypothesis that severe burn trauma corresponding to 30% of total body surface area (TBSA) causes reduction in adenosine triphosphate (ATP) synthesis in distal skeletal muscle. We employed in vivo 31P nuclear magnetic resonance (NMR) in intact mice to assess the rate of ATP synthesis, and characterized the concomitant gene expression patterns in skeletal muscle in burned (30% TBSA) versus control mice. Our NMR results showed a significantly reduced rate of ATP synthesis and were complemented by genomic results showing downregulation of the ATP synthase mitochondrial F1 F0 complex and PGC-1beta gene expression. Our findings suggest that inflammation and muscle atrophy in burns are due to a reduced ATP synthesis rate that may be regulated upstream by PGC-1beta. These findings implicate mitochondrial dysfunction in distal skeletal muscle following burn injury. That PGC-1beta is a highly inducible factor in most tissues and responds to common calcium and cyclic adenosine monophosphate (cAMP) signaling pathways strongly suggests that it may be possible to develop drugs that can induce PGC-1beta.
Tzika
A Aria
AA
Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA. atzika@partners.org
Mintzopoulos
Dionyssios
D
Padfield
Katie
K
Wilhelmy
Julie
J
Mindrinos
Michael N
MN
Yu
Hongue
H
Cao
Haihui
H
Zhang
Qunhao
Q
Astrakas
Loukas G
LG
Zhang
Jiangwen
J
Yu
Yong-Ming
YM
Rahme
Laurence G
LG
Tompkins
Ronald G
RG
D000255:Adenosine Triphosphate / Q000096:biosynthesis*; D000818:Animals; D001830:Body Surface Area; D002056:Burns / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation / Q000235:genetics*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D008954:Models, Biological; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology*; D010085:Oxidative Phosphorylation; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D010759:Phosphorus Isotopes; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors
D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D010759:Phosphorus Isotopes; C485290:Ppargc1a protein, mouse; D012333:RNA, Messenger; D015534:Trans-Activators; D014157:Transcription Factors; D000255:Adenosine Triphosphate