Rottlerin activates AMPK possibly through LKB1 in vascular cells and tissues.
Biochem Biophys Res Commun
; 376(2): 434-8, 2008 Nov 14.
Article
em En
| MEDLINE
| ID: mdl-18789895
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Acetofenonas
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Benzopiranos
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Proteínas Serina-Treonina Quinases
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Inibidores de Proteínas Quinases
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Complexos Multienzimáticos
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Músculo Liso Vascular
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2008
Tipo de documento:
Article