Young-ho Lee

The X-gene product (HBx) of the hepatitis B virus plays essential roles in viral replication and the generation of hepatocellular carcinoma. Although the mechanism for HBx action is unclear, HBx may exert its pleiotropic functions through the stimulation of signal transduction pathways including the Ras/mitogen-activated protein kinase cascade and/or inactivation of the p53 function. Here, we investigated whether HBx has the ability to activate the Jak-STAT signaling pathway. As a first step, we

Nuclear receptors activate transcription by recruiting multiple coactivators to the promoters of specific target genes. The functional synergy of the p160 coactivators [steroid receptor coactivator-1, glucocorticoid receptor interacting protein (GRIP1), or the activator for thyroid hormone and retinoid receptors], the histone acetyltransferases cAMP response element binding protein binding protein (CBP) and p300 and the histone methyltransferase coactivator-associated arginine methyltransferase

The mechanism of phospholipase D (PLD) activation by platelet-derived growth factor (PDGF) was examined using a NIH 3T3 fibroblast cell line (3T3-gamma 1) that stably overexpresses PLC-gamma 1 isozyme. Immunoblot analysis revealed that 3T3-gamma 1 cells contained about 10-fold more PLC-gamma 1 than a control cell line (3T3-C) transfected with expression vector lacking PLC-gamma 1 cDNA. PDGF-stimulated PLD activation was 10-fold greater in 3T3-gamma 1 cells than in 3T3-C cells, indicating that PL

Beta-catenin mediates Wnt/wingless signaling and transcriptional activation by lymphocyte enhancer binding factor 1/T cell factor (LEF1/TCF) proteins with the assistance of multiple coregulators, including positive cofactors like p300/CBP and negative cofactors like HDACs. We previously demonstrated that a developmentally essential protein, Flightless-I (Fli-I), serves as a coactivator for nuclear receptor-mediated transcription. To further understand the action mechanism of Fli-I, we investigat

Endoplasmic reticulum (ER) stress has been shown to play a critical role in the pathogenesis of cardiovascular complications. However, the role and mechanisms of ER stress in hypertension remain unclear. Thus, we hypothesized that enhanced ER stress contributes to the maintenance of hypertension in spontaneously hypertensive rats (SHRs). Sixteen-week old male SHRs and Wistar Kyoto Rats (WKYs) were used in this study. The SHRs were treated with ER stress inhibitor (Tauroursodeoxycholic acid; TUDC

1. The effects on contractility of three peptides reported to inhibit protein kinase C (PKC) translocation in an isozyme-specific manner were studied: a peptide from the C2 domain of conventional PKCs (C2-2), a peptide from the N-terminal variable domain of epsilonPKC (epsilonV1-2) and a peptide (ABP) from the actin-binding domain of epsilonPKC (epsilon(223-228)). 2. Isometric force was directly recorded from individual hyperpermeable ferret portal vein or aortic smooth muscle cells. 3. Phenylep

Our results suggest that ENaC, TRPM4, and TRPC6 play important roles in the pressure-induced myogenic response, and that ENaC and TRPM4 interact in rat PCA.

To assess the functional significance of tethering actin to myosin by caldesmon in the regulation of smooth muscle contraction, we investigated the effects of synthetic peptides, containing the myosin-binding sequences in the N-terminal region of caldesmon, on force directly recorded from single permeabilized smooth muscle cells of ferret portal vein. Two peptides were used, IK29C and MY27C, containing residues from Ile(25) to Lys(53) and from Met(1) to Tyr(27) of the human and chicken caldesmon

Our results suggest that Ca(2+)-independent MLCK activity is enhanced in the SHR, and that ZIPK plays, at least in part, an important role as a candidate for this kinase in rat mesenteric arteries.

NEW FINDINGS: What is the central question of this study? Endoplasmic reticulum (ER) stress has been reported to be involved in type 2 diabetes; however, the role of exacerbated ER stress in vascular dysfunction in type 2 diabetes remains unknown. What is the main finding and its importance? The main findings of this study are that ER stress is increased in the coronary arteries in type 2 diabetes, and inhibition of ER stress using taurine-conjugated ursodeoxycholic acid improves vascular functi

To obtain insight into the motional features of proteins for enzymatic function, we studied binding reactions between ferredoxin-NADP(+) reductase (FNR) and ferredoxin (Fd) using isothermal titration calorimetry and NMR-based magnetic relaxation and hydrogen/deuterium exchange (HD(ex)). Fd-FNR binding was accompanied by endothermic reactions and driven by the entropy gain. Component-wise analysis of the net entropy change revealed that increases in the conformational entropy of the Fd-FNR comple

AIMS: Although stimulation with sphingosylphosphorylcholine (SPC) or sphingosine-1-phosphate (S1P) generally leads to similar vascular responses, the contractile patterns and their underlying signalling mechanisms are often distinct. We investigated the different reliance upon Ca2+-dependent and Ca2+-sensitizing mechanisms of constriction in response to SPC or S1P in coronary arteries. METHODS AND RESULTS: Contractile responses, changes in [Ca2+]i, and phosphorylation of myosin light chain phosp

To investigate whether alpha1-adrenoceptors are involved in pain behaviors in streptozotocin (STZ)-induced diabetic rats, we measured the effects of phenylephrine or prazosin on allodynia in the diabetic rats. Phenylephrine aggravated allodynia, while prazosin alleviated allodynia in the diabetic rats. We also measured alpha1-adrenoceptors gene expression or density of [3H]-prazosin binding sites in the dorsal root ganglia (DRG) and spinal cord in painful diabetic rats. Alpha1-adrenoceptors mRNA

Comment on: Lee YH, et al. Genes Dev 2011; 25:176-88.