Abstract:
: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.
journal_name
Biochem Biophys Res Communjournal_title
Biochemical and biophysical research communicationsauthors
Zhao B,Shen H,Zhang L,Shen Ydoi
10.1016/j.bbrc.2012.06.078subject
Has Abstractpub_date
2012-07-20 00:00:00pages
100-4issue
1eissn
0006-291Xissn
1090-2104pii
S0006-291X(12)01173-4journal_volume
424pub_type
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