Acute exercise activates AMPK and eNOS in the mouse aorta

被引:64
作者
Cacicedo, Jose M. [2 ,3 ,4 ]
Gauthier, Marie-Soleil [2 ,3 ]
Lebrasseur, Nathan K. [2 ,3 ]
Jasuja, Ravi [2 ,3 ]
Ruderman, Neil B. [1 ,2 ,3 ]
Ido, Yasuo [2 ,3 ]
机构
[1] Boston Univ, Sch Med, Diabet & Metab Res Unit, BUSM, Boston, MA 02118 USA
[2] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA
[3] Boston Univ, Sch Med, Endocrinol Sect, Boston, MA 02118 USA
[4] Boston Univ, Sch Med, Dept Pathol & Lab Med, Boston, MA 02118 USA
来源
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY | 2011年 / 301卷 / 04期
关键词
adenosine 5 '-monophosphate-activated protein kinase; endothelial nitric oxide synthase; NITRIC-OXIDE SYNTHASE; PROTEIN-KINASE ACTIVATION; VASCULAR ENDOTHELIAL-CELLS; TYPE-2; DIABETES-MELLITUS; SHEAR-STRESS; ACCELERATED ATHEROSCLEROSIS; INSULIN SENSITIVITY; OXIDATIVE STRESS; NAD(P)H OXIDASE; DEFICIENT MICE;
D O I
10.1152/ajpheart.01279.2010
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Cacicedo JM, Gauthier MS, Lebrasseur NK, Jasuja R, Ruderman NB, Ido Y. Acute exercise activates AMPK and eNOS in the mouse aorta. Am J Physiol Heart Circ Physiol 301: H1255-H1265, 2011. First published July 1, 2011; doi: 10.1152/ajpheart.01279.2010.-Exercise can prevent endothelial cell (EC) dysfunction and atherosclerosis even in the absence of improvements in plasma lipids. However, the mechanisms responsible for these effects are incompletely understood. In this study we examined in mice whether an acute bout of exercise activates enzymes that could prevent EC dysfunction, such as AMP-activated protein kinase (AMPK) and endothelial nitric oxide synthase (eNOS). We also examined whether exercise alters known regulators of these enzymes. C57BL/6 mice underwent a single bout of exhaustive treadmill exercise after which their aortas were analyzed for activation of AMPK, AMPK regulatory proteins, eNOS, and various enzymes that, like AMPK, activate eNOS. We found that such exercise acutely activates both AMPK and eNOS in the whole aorta and that the magnitude of these effects correlated with both the distance run and activation of the AMPK regulatory proteins silent information regulator-1 (SIRT1)-LKB1 and CaMKK beta. In contrast, Akt, PKA, PKG, and Src, other kinases known to activate eNOS, were unaffected. Immunohistochemical analysis revealed that AMPK and eNOS were both activated in the ECs of the aorta. This study provides the first evidence that an acute bout of exercise activates AMPK and eNOS in the endothelium of the aorta. The results also suggest that AMPK likely is the principal activator of eNOS in this setting and that its own activation may be mediated by both SIRT1-LKB1 and CaMKK beta.
引用
收藏
页码:H1255 / H1265
页数:11
相关论文
共 57 条
[41]   MUSCLE GLUCOSE-METABOLISM FOLLOWING EXERCISE IN THE RAT - INCREASED SENSITIVITY TO INSULIN [J].
RICHTER, EA ;
GARETTO, LP ;
GOODMAN, MN ;
RUDERMAN, NB .
JOURNAL OF CLINICAL INVESTIGATION, 1982, 69 (04) :785-793
[42]   AMP kinase and malonyl-CoA: Targets for therapy of the metabolic syndrome [J].
Ruderman, N ;
Prentki, M .
NATURE REVIEWS DRUG DISCOVERY, 2004, 3 (04) :340-351
[43]   AMPK as a metabolic switch in rat muscle, liver and adipose tissue after exercise [J].
Ruderman, NB ;
Park, H ;
Kaushik, VK ;
Dean, D ;
Constant, S ;
Prentki, M ;
Saha, AK .
ACTA PHYSIOLOGICA SCANDINAVICA, 2003, 178 (04) :435-442
[44]   Malonyl-CoA and AMP-activated protein kinase (AMPK): possible links between insulin resistance in muscle and early endothelial cell damage in diabetes [J].
Ruderman, NB ;
Cacicedo, JM ;
Itani, S ;
Yagihashi, N ;
Saha, AK ;
Ye, JM ;
Chen, K ;
Zou, M ;
Carling, D ;
Boden, G ;
Cohen, RA ;
Keaney, J ;
Kraegen, EW ;
Ido, Y .
BIOCHEMICAL SOCIETY TRANSACTIONS, 2003, 31 :202-206
[45]   Physical activity/exercise and type 2 diabetes - A consensus statement from the American diabetes association [J].
Sigal, Ronald J. ;
Kenny, Glen P. ;
Wasserman, David H. ;
Castaneda-Sceppa, Carmen ;
White, Russell D. .
DIABETES CARE, 2006, 29 (06) :1433-1438
[46]  
Skerrett P., 2002, Handbook of exercise in diabetes, P155
[47]   Decreased arteriolar sensitivity to shear stress in adult rats is reversed by chronic exercise activity [J].
Sun, D ;
Huang, A ;
Koller, A ;
Kaley, G .
MICROCIRCULATION, 2002, 9 (02) :91-97
[48]   Statins activate AMP-activated protein kinase in vitro and in vivo [J].
Sun, Wei ;
Lee, Tzong-Shyuan ;
Zhu, Minjia ;
Gu, Chunang ;
Wang, Yinsheng ;
Zhu, Yi ;
Shyy, John Y-J. .
CIRCULATION, 2006, 114 (24) :2655-2662
[49]   Endurance exercise increases the SIRT1 and peroxisome proliferator-activated receptor γ coactivator-1α protein expressions in rat skeletal muscle [J].
Suwa, Masataka ;
Nakano, Hiroshi ;
Radak, Zsolt ;
Kumagai, Shuzo .
METABOLISM-CLINICAL AND EXPERIMENTAL, 2008, 57 (07) :986-998
[50]   Hydrogen peroxide activates endothelial nitric-oxide synthase through coordinated phosphorylation and dephosphorylation via a phosphoinositide 3-kinase-dependent signaling pathway [J].
Thomas, SR ;
Chen, K ;
Keaney, JF .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (08) :6017-6024