Learn More
Adiponectin (Ad) is a hormone secreted by adipocytes that regulates energy homeostasis and glucose and lipid metabolism. However, the signaling pathways that mediate the metabolic effects of Ad remain poorly identified. Here we show that phosphorylation and activation of the 5'-AMP-activated protein kinase (AMPK) are stimulated with globular and full-length(More)
SEA0400 is a potent and selective Na(+)/Ca(2+) exchanger (NCX) inhibitor. We evaluated the inhibitory effects of SEA0400 on Na(+)(i)-dependent (45)Ca(2+) uptake and whole-cell Na(+)/Ca(2+) exchange currents in NCX-transfected fibroblasts. SEA0400 preferentially inhibited (45)Ca(2+) uptake by NCX1 compared with inhibitions by NCX2, NCX3, and NCKX2. SEA0400(More)
KB-R7943 (2-[2-[4-(4-nitrobenzyloxy)phenyl]ethyl]isothiourea methanesulfonate) is a potent and selective Na(+)/Ca(2+) exchange (NCX) inhibitor that is 3-fold more inhibitory to NCX3 than to NCX1 or NCX2. Here we searched for amino acid residues that may form the KB-R7943 receptor in the exchanger by analyzing the function of chimeras between NCX1 and NCX3(More)
Ca(2+)/cation antiporters catalyze the exchange of Ca(2+) with various cations across biological membranes to regulate cytosolic calcium levels. The recently reported structure of a prokaryotic Na(+)/Ca(2+) exchanger (NCX_Mj) revealed its overall architecture in an outward-facing state. Here, we report the crystal structure of a H(+)/Ca(2+) exchanger from(More)
We investigated the properties and interaction domains of SN-6 [2-[4-(4-nitrobenzyloxy)benzyl]thiazolidine-4-carboxylic acid ethyl ester], a newly synthesized and selective Na /Ca exchange (NCX) inhibitor. SN-6 (0.3–30 M) inhibited preferentially intracellular Na -dependent Ca uptake (i.e., the reverse mode) compared with extracellular Na -dependent Ca(More)
We created knock-in mice in which a deletion of 3 base pairs coding for K210 in cardiac troponin (cTn)T found in familial dilated cardiomyopathy patients was introduced into endogenous genes. Membrane-permeabilized cardiac muscle fibers from mutant mice showed significantly lower Ca(2+) sensitivity in force generation than those from wild-type mice. Peak(More)
The membrane domain of the Na(+)/Ca(2+) exchanger (NCX) contains two conserved internal repeat sequences, designated the alpha-1 and alpha-2 repeats. We have studied the topological disposition of residues in the alpha repeats and a neighboring region by substituted cysteine accessibility scanning as well as the functional importance of these residues by(More)
Bradykinin (BK) is produced and acts at the site of injury and inflammation. In the CNS, migration of microglia toward the lesion site plays an important role pathologically. In the present study, we investigated the effect of BK on microglial migration. Increased motility of cultured microglia was mimicked by B1 receptor agonists and markedly inhibited by(More)
The Na(+)/Ca(2+) exchanger (NCX) is a bidirectional transporter that normally extrudes Ca(2+) from the cell (forward mode), but also brings Ca(2+) into the cell (reverse mode) under special conditions such as intracellular Na(+) (Na(+)(i)) accumulation or membrane depolarization. There are three mammalian NCX isoforms: NCX1 is widely expressed in the heart,(More)
Excessive salt intake is a major risk factor for hypertension. Here we identify the role of Na(+)/Ca(2+) exchanger type 1 (NCX1) in salt-sensitive hypertension using SEA0400, a specific inhibitor of Ca(2+) entry through NCX1, and genetically engineered mice. SEA0400 lowers arterial blood pressure in salt-dependent hypertensive rat models, but not in other(More)