Gambogic acid activates AMP-activated protein kinase in mammalian cells.
AMP-activated protein kinase (AMPK) plays a key role in maintaining intracellular and whole-body energy homeostasis. Activation of AMPK has been shown to ameliorate the symptoms of metabolic diseases, such as type 2 diabetes and obesity. Here we show that gambogic acid (GB), a known antitumor agent, activates AMPK by increasing the phosphorylation of AMPKα and its downstream substrate ACC in various cell lines. Further study revealed that GB stimulated AMPK activity independent of upstream kinases. Moreover, the AMPK inhibitor, compound C, has no effects on the GB-induced AMPK activation. We also found that GB promptly increased intracellular ROS level, and antioxidants attenuated the ROS production. Interestingly, only the thiol antioxidants significantly abolished GB-enhanced AMPK activation. In addition, analysis of binding and dissociation kinetics indicated that GB bound to the AMPKα subunit. Collectively, these results suggest that GB may be a novel direct activator of AMPK.
State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, Fujian 361005, PR China.
Baobing
B
Zhao
Huili
H
Shen
Lianru
L
Zhang
Yuemao
Y
Shen
D055372:AMP-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002460:Cell Line; D051379:Mice; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D044004:Xanthones / Q000494:pharmacology*
D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D017382:Reactive Oxygen Species; D044004:Xanthones; C052659:gambogic acid; D055372:AMP-Activated Protein Kinases