AMPK induces vascular smooth muscle cell senescence via LKB1 dependent pathway

Journal Article · Fri Sep 16 04:00:00 EDT 2011 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/J.BBRC.2011.08.071· OSTI ID:22207500

Sung, Jin Young; Woo, Chang-Hoon ^[1]; Kang, Young Jin; Lee, Kwang Youn ^[1]

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1. Department of Pharmacology, College of Medicine, Yeungnam University, Daegu 705-717 (Korea, Republic of)

Highlights: {yields} An aging model was established by stimulating VSMC with adriamycin. {yields} Adriamycin increased p-LKB1, p-AMPK, p53 and p21 expressions. {yields} Inhibition of AMPK diminished SA-{beta}-gal staining and restored VSMC proliferation. {yields} p53 and p21 siRNA attenuated adriamycin-induced SA-{beta}-gal staining in VSMC. {yields} p53-p21 pathway is a mediator of LKB1/AMPK induced VSMC senescence. -- 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.

• OSTI ID: 22207500
• Journal Information: Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 1 Vol. 413; ISSN 0006-291X; ISSN BBRCA9
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
AGING
AMP
CARBOXYLASE
CELL PROLIFERATION
DISEASES
DOXORUBICIN
GALACTOSIDASE
INHIBITION
MESSENGER-RNA
MONOCLINIC LATTICES
MUSCLES
PHOSPHORUS 21
PHOSPHORYLATION
STIMULATION
TRANSLOCATION