Rottlerin activates AMPK possibly through LKB1 in vascular cells and tissues.
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.
Kojima
Kanou
K
Department of Metabolic Medicine, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, Japan.
Motoshima
Hiroyuki
H
Tsutsumi
Atsuyuki
A
Igata
Motoyuki
M
Matsumura
Takeshi
T
Kondo
Tatsuya
T
Kawashima
Junji
J
Ichinose
Kenshi
K
Furukawa
Noboru
N
Inukai
Kouichi
K
Katayama
Shigehiro
S
Goldstein
Barry J
BJ
Nishikawa
Takeshi
T
Tsuruzoe
Kaku
K
Araki
Eiichi
E
D000091162:AMP-Activated Protein Kinase Kinases; D055372:AMP-Activated Protein Kinases; D000098:Acetophenones / Q000494:pharmacology*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001011:Aorta / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D001578:Benzopyrans / Q000494:pharmacology*; D002478:Cells, Cultured; D004789:Enzyme Activation; D006801:Humans; D009097:Multienzyme Complexes / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D051745:Protein Kinase C-delta / Q000037:antagonists & inhibitors / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*; D011817:Rabbits
D000098:Acetophenones; D001578:Benzopyrans; D009097:Multienzyme Complexes; D047428:Protein Kinase Inhibitors; D000255:Adenosine Triphosphate; C085746:rottlerin; D017346:Protein Serine-Threonine Kinases; C109790:STK11 protein, human; D051745:Protein Kinase C-delta; D000091162:AMP-Activated Protein Kinase Kinases; D055372:AMP-Activated Protein Kinases