Protective effects of AMP-activated protein kinase in the cardiovascular system.
Bottom Line: AMPK is found in most mammalian tissues, including those of the cardiovascular system.Recent studies have provided proof of concept for the idea that AMPK is protective in heart as well as in vascular endothelial and smooth muscle cells.The roles of AMPK in the cardiovascular system, as they are currently understood, will be presented in this review.
Affiliation: Department of Geriatrics, Southwest Hospital, Third Military Medical University, Chongqing, China.Show MeSH
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Mentions: The phosphorylation of the sites referred to above is regulated by three upstream AMPK kinases (AMPKKs): LKB1, Ca2+/calmodulin-dependent protein kinase β (CaMKKβ) and transforming growth factor β activated kinase 1 (TAK1) shown schematically in Fig. 1. LKB1 is an upstream AMPKK that regulates AMPK and AMP-related kinases  and is believed to be the most potent positive regulator of AMPK [26, 27]. A cytosolic protein complex containing LKB1, putative kinase STRAD and the MO25 scaffold protein can interact with, and directly phosphorylate, AMPK . When the AMP/ATP ratio increases, the phosphorylation of AMPK by LKB1 is enhanced; the LKB1 pathway is thought to be the major route by which AMPK is activated in response to energy demand and to maintain metabolic homeostasis. In addition, an increasing number of studies indicate that LKB1 is the principal provider of AMPKK activity, especially in peripheral tissues such as muscle, adipose tissue and liver. The second AMPKK, CaMKKβ, is particularly relevant to situations where Ca2+ signalling pathways are activated. Several studies have shown that Ca2+ signalling activates AMPK by CaMKKβ-dependent phosphorylation [28–30]. Some investigators have suggested that the CaMKKβ–AMPK axis plays an important role in cerebral Ca2+ signal transduction under physiological conditions as well as in ischaemic states (e.g., ischaemia-induced calcium influx through NMDA receptor activation) [31, 32]. Recently, TAK1, the third putative upstream AMPKK, (also referred to as MAPKK kinase-7 or MAP3K7) was identified by Momcilovic et al.[33, 34]. Subsequently, TAK1 has been shown to activate AMPK-dependent cytoprotective autophagy in tumour necrosis factor (TNF)-related apoptosis-inducing ligand-treated epithelial cells . However, the precise role of TAK1 as an AMPKK requires further investigation.
Affiliation: Department of Geriatrics, Southwest Hospital, Third Military Medical University, Chongqing, China.