AI Article Synopsis
- AMP-activated protein kinase (AMPK) plays a key role as a cellular energy sensor and is a potential therapeutic target for vascular diseases.
- The study investigated the impact of rottlerin, a known inhibitor of protein kinase Cdelta, on AMPK activation in vascular smooth muscle cells and isolated rabbit aorta, finding that rottlerin reduces ATP levels and activates AMPK.
- Results indicate that the presence of LKB1 is crucial, as overexpressing a dominant-negative form of LKB1 reduced AMPK activation, suggesting LKB1 mediates the effects of rottlerin on AMPK in vascular tissues.
Article Abstract
AMP-activated protein kinase (AMPK) is a cellular energy sensor involved in multiple cell signaling pathways that has become an attractive therapeutic target for vascular diseases. It is not clear whether rottlerin, an inhibitor of protein kinase Cdelta, activates AMPK in vascular cells and tissues. In the present study, we have examined the effect of rottlerin on AMPK in vascular smooth muscle cells (VSMCs) and isolated rabbit aorta. Rottlerin reduced cellular ATP and activated AMPK in VSMCs and rabbit aorta; however, inhibition of PKCdelta by three different methods did not activate AMPK. Both VSMCs and rabbit aorta expressed the upstream AMPK kinase LKB1 protein, and rottlerin-induced AMPK activation was decreased in VSMCs by overexpression of dominant-negative LKB1, suggesting that LKB1 is involved in the upstream regulation of AMPK stimulated by rottlerin. These data suggest for the first time that LKB1 mediates rottlerin-induced activation of AMPK in vascular cells and tissues.
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| http://dx.doi.org/10.1016/j.bbrc.2008.09.007 | DOI Listing |
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