AMPK induces vascular smooth muscle cell senescence via LKB1 dependent pathway

Title
AMPK induces vascular smooth muscle cell senescence via LKB1 dependent pathway
Author(s)
최형철성진영우창훈강영진이광윤
Keywords
ACTIVATED PROTEIN-KINASE; ENDOTHELIAL-CELLS; OXIDATIVE STRESS; TUMOR-SUPPRESSOR; ATHEROSCLEROSIS; PROLIFERATION; DISEASE; SURVIVAL; SIRT1
Issue Date
201109
Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
Citation
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, v.413, no.1, pp.143 - 148
Abstract
Vascular cells have a limited lifespan with limited cell proliferation and undergo cellular senescence. The functional changes associated with cellular senescence are thought to contribute to age-related vascular disorders. AMP-activated protein kinase (AMPK) has been discussed in terms of beneficial or harmful effects for aging-related diseases. However, the detailed functional mechanisms of AMPK are largely unclear. An aging model was established by stimulating vascular smooth muscle cell (VSMC) with adriamycin. Adriamycin progressively increased the mRNA and protein expressions of AMPK. The phosphorylation levels of LKB1 and acetyl-CoA carboxylase (ACC), the upstream and downstream of AMPK, were dramatically increased by adriamycin stimulation. The expressions of p53 and p21, which contribute to vascular senescence, were also increased. Inhibition of AMPK diminished senescence-associated beta-galactosidase (SA-beta-gal) staining, and restored VSMC proliferation. Cytosolic translocation of LKB1 by adriamycin could be a mechanism for AMPK activation in senescence. Furthermore, p53 siRNA and p21 siRNA transfection attenuated adriamycin-induced SA-beta-gal staining. These results suggest that LKB1 dependent AMPK activation elicits VSMC senescence and p53-p21 pathway is a mediator of LKB1/AMPK-induced senescence. (C) 2011 Elsevier Inc. All rights reserved.
URI
http://hdl.handle.net/YU.REPOSITORY/24624http://dx.doi.org/10.1016/j.bbrc.2011.08.071
ISSN
0006-291X
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의과대학 > 약리학교실 > Articles
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