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AMP kinase/cyclic AMP/PK‐A crosstalk in vascular smooth muscle
Author(s) -
Stone Joshua Daniel,
Narine Avinash,
Tulis David Anthony
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.1026.22
Subject(s) - ampk , protein kinase a , vascular smooth muscle , phosphorylation , activator (genetics) , amp activated protein kinase , endocrinology , chemistry , medicine , adenosine monophosphate , microbiology and biotechnology , adenosine , biochemistry , biology , receptor , smooth muscle
Aberrant vascular smooth muscle cell (VSMC) growth is pivotal in the pathophysiology of vessel disease. We previously reported that the cyclic AMP/PK‐A system has capacity to attenuate growth of serum‐stimulated rat A7R5 VSMCs. Considering the common utilization of a 5′‐AMP substrate, in the current study we hypothesize that regulatory crosstalk occurs between adenosine monophosphate‐activated protein kinase (AMPK) and the cyclic AMP/PK‐A signaling cascades in VSM. Incubation of rat primary VSMCs with the AMPK activator AICAR significantly increased phosphorylation of both a catalytic Thr172 site and a proposed inhibitory Ser485 residue on AMPK. Concomitantly, we observed increases in AMPK activity shown by both phosphorylation of the downstream target Acetyl CoA Carboxylase (ACC) at Ser80 and an AMPK activity assay. These events were completely abridged by both the AMPK and PKA inhibitors Compound C (CC) and PKI, respectively. AICAR also induced CC‐ and PKI‐inhibitable PK‐A activation measured by vasodilator‐stimulated phosphoprotein (VASP) phosphorylation at Thr157 and a PK‐A activity assay. Lastly, preliminary flow cytometry results suggest that AMPK activity inhibits cell cycle progression from G 0 /G 1 . These provocative findings reveal a discrete nexus between AMPK and cyclic AMP/PK‐A in VSMCs and lend credence for a potential metabolic target for quelling abnormal VSMC growth.