title: AMPK induces vascular smooth muscle cell senescence via LKB1 dependent pathway.
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 β-galactosidase (SA-β-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-β-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.
authors.affiliation: Department of Pharmacology, College of Medicine, Yeungnam University, Daegu 705-717, Republic of Korea.717, Republic of Korea.
authors.forename: Jin Young
authors.initials: JY
authors.lastname: Sung
authors.forename: Chang-Hoon
authors.initials: CH
authors.lastname: Woo
authors.forename: Young Jin
authors.initials: YJ
authors.lastname: Kang
authors.forename: Kwang Youn
authors.initials: KY
authors.lastname: Lee
authors.forename: Hyoung Chul
authors.initials: HC
authors.lastname: Choi
mesh_terms: D000091162:AMP-Activated Protein Kinase Kinases; D055372:AMP-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000818:Animals; D049109:Cell Proliferation; D002478:Cells, Cultured; D016922:Cellular Senescence; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D017346:Protein Serine-Threonine Kinases; C488755:Stk11 protein, rat; D000091162:AMP-Activated Protein Kinase Kinases; D055372:AMP-Activated Protein Kinases