Activation of AMPK attenuates LPS-induced acute lung injury by upregulation of PGC1α and SOD1.
Evidence suggests that an imbalance between oxidation and antioxidation is involved in the pathogenesis of acute lung injury/acute respiratory distress syndrome (ALI/ARDS). Activation of AMP-activated protein kinase (AMPK) has been shown to inhibit the occurrence of ALI/ARDS. However, it is unknown whether activation of AMPK benefits ALI/ARDS by restoration of the oxidant and antioxidant balance, and which mechanisms are responsible for this process. The present study aimed to address these issues. Lipopolysaccharide (LPS) induced pronounced pathological changes of ALI in mice; these were accompanied by elevated production of malondialdehyde (MDA) and decreased activity of superoxide dismutase (SOD) compared with control mice. Prior treatment of mice with the AMPK agonist metformin significantly suppressed the LPS-induced development of ALI, reduced the elevation of MDA and increased the activity of SOD. Further analysis indicated that activation of AMPK also stimulated the protein expression of peroxisome proliferator-activated receptor γ coactivator 1α (PGC1α) and superoxide dismutase 1 (SOD1). This study suggests that activation of AMPK by metformin inhibits oxidative stress by upregulation of PGC1α and SOD1, thereby suppressing the development of ALI/ARDS, and has potential value in the clinical treatment of such conditions.
Department of Respiratory Internal Medicine, The First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shanxi 710061, P.R. China.
Guizuo
G
Wang
Department of Respiratory Internal Medicine, The First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shanxi 710061, P.R. China.
Yang
Y
Song
Department of Respiratory Internal Medicine, The First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shanxi 710061, P.R. China.
Wei
W
Feng
Department of Respiratory Internal Medicine, The First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shanxi 710061, P.R. China.
Lu
L
Liu
Department of Respiratory Internal Medicine, The First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shanxi 710061, P.R. China.
Yanting
Y
Zhu
Department of Respiratory Internal Medicine, The First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shanxi 710061, P.R. China.
Xinming
X
Xie
Department of Respiratory Internal Medicine, The First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shanxi 710061, P.R. China.
Yilin
Y
Pan
Department of Respiratory Internal Medicine, The First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shanxi 710061, P.R. China.
Rui
R
Ke
Department of Respiratory Internal Medicine, The First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shanxi 710061, P.R. China.
Shaojun
S
Li
Department of Respiratory Internal Medicine, The First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shanxi 710061, P.R. China.
Fangwei
F
Li
Department of Respiratory Internal Medicine, The First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shanxi 710061, P.R. China.
Lan
L
Yang
Department of Respiratory Internal Medicine, The First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shanxi 710061, P.R. China.
Manxiang
M
Li
AMP-activated protein kinase; acute lung injury; peroxisome proliferator-activated receptor γ coactivator 1α; superoxide dismutase 1