CaMKK beta Is Involved in AMP-Activated Protein Kinase Activation by Baicalin in LKB1 Deficient Cell Lines

doi:10.1371/journal.pone.0047900

	CaMKK beta Is Involved in AMP-Activated Protein Kinase Activation by Baicalin in LKB1 Deficient Cell Lines
	Ma, Ying; Yang, Fuzhen; Wang, Ying; Du, Zhiyan; Liu, Daihua; Guo, Hongxia; Shen, Jingkang; Peng, Hongli
刊名	PLOS ONE
	2012-10-22
卷号	7 期号:10
ISSN号	1932-6203
DOI	10.1371/journal.pone.0047900
文献子类	Article
英文摘要	AMP-activated protein kinase (AMPK) plays an important role in mediating energy metabolism and is controlled mainly by two upstream kinases, LKB1 or Ca2+/calmodulin-dependent protein kinase kinase-beta (CaMKK beta). Previously, we found that baicalin, one of the major flavonoids in a traditional Chinese herb medicine, Scutellaria baicalensis, protects against the development of hepatic steatosis in rats feeding with a high-fat diet by the activation of AMPK, but, the underlying mechanism for AMPK activation is unknown. Here we show that in two LKB1-deficient cells, HeLa and A549 cells, baicalin activates AMPK by alpha Thr-172 phosphorylation and subsequent phosphorylation of its downstream target, acetyl CoA carboxylase, at Ser-79, to a similar degree as does in HepG2 cells (that express LKB1). Pharmacologic inhibition of CaMKK beta by its selective inhibitor STO-609 markedly inhibits baicalin-induced AMPK activation in both HeLa and HepG2 cells, indicating that CaMKK beta is the responsible AMPK kinase. We also show that treatment of baicalin causes a larger increase in intracellular Ca2+ concentration ([Ca2+](i)), although the maximal level of [Ca2+](i) is lower in HepG2 cells compared to HeLa cells. Chelation of intracellular free Ca2+ by EDTA and EGTA, or depletion of intracellular Ca2+ stores by the endoplasmic reticulum Ca2+-ATPase inhibitor thapsigargin abrogates baicalin-induced activation of AMPK in HeLa cells. Neither cellular ATP nor the production of reactive oxygen species is altered by baicalin. Finally, in HeLa cells, baicalin treatment no longer decreases intracellular lipid accumulation caused by oleic acid after inhibition of CaMKK beta by STO-609. These results demonstrate that a potential Ca2+/CaMKK beta dependent pathway is involved in the activation of AMPK by baicalin and suggest that CaMKK beta likely acts as an upstream kinase of AMPK in response to baicalin.
资助项目	National Natural Science Foundation of China[81172921] ; National Natural Science Foundation of China[30672467]
WOS关键词	SCUTELLARIA-BAICALENSIS GEORGI ; LIPID-ACCUMULATION ; HEPATIC STEATOSIS ; INDUCED APOPTOSIS ; OXIDATIVE STRESS ; SKELETAL-MUSCLE ; UPSTREAM KINASE ; CANCER-CELLS ; HEPG2 CELLS ; PATHWAY
WOS研究方向	Science & Technology - Other Topics
语种	英语
出版者	PUBLIC LIBRARY SCIENCE
WOS记录号	WOS:000310193400022
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/277906]
专题	药物化学研究室中科院受体结构与功能重点实验室新药研究国家重点实验室
通讯作者	Peng, Hongli
作者单位	Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 200031, Peoples R China
推荐引用方式 GB/T 7714	Ma, Ying,Yang, Fuzhen,Wang, Ying,et al. CaMKK beta Is Involved in AMP-Activated Protein Kinase Activation by Baicalin in LKB1 Deficient Cell Lines[J]. PLOS ONE,2012,7(10).
APA	Ma, Ying.,Yang, Fuzhen.,Wang, Ying.,Du, Zhiyan.,Liu, Daihua.,...&Peng, Hongli.(2012).CaMKK beta Is Involved in AMP-Activated Protein Kinase Activation by Baicalin in LKB1 Deficient Cell Lines.PLOS ONE,7(10).
MLA	Ma, Ying,et al."CaMKK beta Is Involved in AMP-Activated Protein Kinase Activation by Baicalin in LKB1 Deficient Cell Lines".PLOS ONE 7.10(2012).