Abstract:
:The prevalence rate of cardiovascular disease is higher for males than females, and estradiol (E2) induces AMP-activated protein kinase (AMPK) activation, which is known to regulate proliferation of VSMC. We identified the estrogenic properties of nordihydroguaiaretic acid (NDGA, a lignan phytoestrogen) that inhibit VSMC proliferation and explored the underlying mechanisms. Both the phosphorylation and expression of LKB1 were increased by NDGA. In addition, NDGA significantly attenuated angiotensin II (Ang II)-induced VSMC proliferation. To elucidate the estrogenic effects, we confirmed that NDGA increased estrogen receptor α (ERα) expression, similar to treatment with E2 and estriol (E3). Furthermore, tamoxifen and ERα siRNA obstructed the effects of NDGA including ERα expression, AMPK phosphorylation and both LKB1 phosphorylation and expression. VSMC proliferation was restored by tamoxifen and ERα siRNA. LKB1 siRNA also reversed the NDGA-mediated inhibition of VSMC proliferation. The estrogenic activity of NDGA induced LKB1 translocation from nucleus to cytosol, and tamoxifen obstructed LKB1 translocation. The absence of LKB1 completely abolished the increase of ERα expression induced by NDGA. Taken together, the beneficial effects of estrogenic compound (E2 and NDGA) on inhibition of VSMC proliferation are mediated by interaction between LKB1 and ERα, suggesting a potential mechanism for females having less cardiovascular disease.
journal_name
J Pharmacol Scijournal_title
Journal of pharmacological sciencesauthors
Kim SA,Lee KY,Kim JR,Choi HCdoi
10.1016/j.jphs.2016.09.001subject
Has Abstractpub_date
2016-09-01 00:00:00pages
78-85issue
1eissn
1347-8613issn
1347-8648pii
S1347-8613(16)30115-3journal_volume
132pub_type
杂志文章abstract::There are several animal models of glucocorticoid-induced osteoporosis (GIOP), but each requires a long time to evaluate drug effects. Zebrafish scales are classified as dermal bone and potentially represent a convenient animal model of GIOP because they rapidly regenerate following their removal. We clarified that de...
journal_title:Journal of pharmacological sciences
pub_type: 杂志文章
doi:10.1016/j.jphs.2020.02.011
更新日期:2020-06-01 00:00:00
abstract::In the present study, we investigated the effect of aripiprazole, a dopamine system stabilizer, on ethanol-induced psychological and physiological dependence and anxiety-like behavior. First we determined the effect of aripiprazole, a dopamine system stabilizer, on the development and expression of ethanol-induced pla...
journal_title:Journal of pharmacological sciences
pub_type: 杂志文章
doi:10.1254/jphs.11201fp
更新日期:2012-01-01 00:00:00
abstract::Epigenetics is a mechanism that regulates gene expression not depending on the underlying DNA sequence, but on the chemical modifications of DNA and histone proteins. Defects in the factors involved in epigenetic regulation cause congenital neurodevelopmental diseases, and thus, epigenetic regulation is essential for ...
journal_title:Journal of pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1254/jphs.09r20fm
更新日期:2010-01-01 00:00:00
abstract::The mechanisms of action of acupuncture and moxibustion as reported by Japanese researchers are reviewed. The endogenous opioid-mediated mechanisms of electroacupuncture (EA) as used in China are well understood, but these are only one component of all mechanisms of acupuncture. These studies emphasize the similarity ...
journal_title:Journal of pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1254/jphs.crj06004x
更新日期:2006-01-01 00:00:00
abstract::We investigated the participation of gamma-aminobutyric acid (GABA) neurons of the medial septal area in eight-arm radial maze performance in rats. The intra-septal injection of muscimol, a GABA(A) agonist, caused an increase in total error and working memory error. On the other hand, no significant effect was observe...
journal_title:Journal of pharmacological sciences
pub_type: 杂志文章
doi:10.1254/jphs.fp0061472
更新日期:2007-07-01 00:00:00
abstract::Based on the structure of AAP, a novel anti-thrombotic peptide from snake venom which we discovered in our previous study, more than 60 compounds were designed and synthesized. One of these termed as LX0702 exhibited stronger anti-platelet aggregation activity than AAP. This study aims to investigate the effects of LX...
journal_title:Journal of pharmacological sciences
pub_type: 杂志文章
doi:10.1016/j.jphs.2015.03.010
更新日期:2015-04-01 00:00:00
abstract::Idiopathic pulmonary fibrosis (IPF) is a progressive and lethal lung disease characterized by inflammation, multifocal fibrotic lesions and excessive collagen deposition with limited therapies. As a major bioactive compound in garlic, S-allyl-l-cysteine (SAC) is a neuroprotective drug candidate to prevent cognitive de...
journal_title:Journal of pharmacological sciences
pub_type: 杂志文章
doi:10.1016/j.jphs.2019.03.002
更新日期:2019-04-01 00:00:00
abstract::Pulmonary arterial hypertension (PAH) is defined as elevation of mean pulmonary arterial pressure to ≥25 mmHg within the low pressure pulmonary circulatory system. PAH is characterized by obstructive vascular remodeling, partially due to excessive pulmonary arterial smooth muscle cell (PASMC) proliferation. Puerarin i...
journal_title:Journal of pharmacological sciences
pub_type: 杂志文章
doi:10.1016/j.jphs.2019.09.010
更新日期:2019-10-01 00:00:00
abstract::We investigated the effects of treatment with trimethyltin (TMT) on the expression of glutathione-related enzymes in mouse hippocampus. TMT promoted the expression of glutathione S-transferase (GST) Ya/Yc mRNA, and GSTA2 protein, but not that of glutamate-cysteine ligase catalytic subunit mRNA, 1 day after injection. ...
journal_title:Journal of pharmacological sciences
pub_type: 历史文章,杂志文章
doi:10.1254/jphs.09158sc
更新日期:2010-01-01 00:00:00
abstract::Simultaneous administration of psychostimulants and opioids is a major drug abuse problem worldwide. This combination appears to produce synergistic effects on behavior at low doses; however, there is little direct evidence that the combination is stronger than either drug alone. Therefore, we investigated interaction...
journal_title:Journal of pharmacological sciences
pub_type: 杂志文章
doi:10.1254/jphs.fpj04039x
更新日期:2004-12-01 00:00:00
abstract::2-Aminophenoxazine-3-one (Phx-3) induced cellular apoptosis in mouse melanoma B16 cells as detected by DNA laddering and upregulated Fas expression in the cells in vitro. Next, the anti-metastatic effects of Phx-3 were investigated in C56BL/6 mice. When B16 melanoma cells were injected into the tail veins of mice, sig...
journal_title:Journal of pharmacological sciences
pub_type: 杂志文章
doi:10.1254/jphs.10023fp
更新日期:2010-01-01 00:00:00
abstract::Clinically, hemorrhoidal bleeding and prolapse disappeared immediately after injection of the sclerosing agent OC-108 into submucosa of hemorrhoids. The aim of this study was to elucidate the mechanism of action responsible for the immediate hemostatic effect of OC-108 using anesthetized rats. Subcutaneous injection o...
journal_title:Journal of pharmacological sciences
pub_type: 杂志文章
doi:10.1254/jphs.fp0060583
更新日期:2006-11-01 00:00:00
abstract::A simple in vivo closed-chest atrial fibrillation (Af) model of rats was developed. Af was reproducibly induced by transesophageal atrial burst pacing for 30 s in each of the pentobarbital-anesthetized rats, whereas the cardiohemodynamic condition as well as the inducibility and duration of Af episode was stable over ...
journal_title:Journal of pharmacological sciences
pub_type: 杂志文章
doi:10.1254/jphs.scj05002x
更新日期:2005-07-01 00:00:00
abstract::L-Dihydroxyphenylalanine (L-DOPA) is considered the gold standard for the treatment of Parkinson's disease (PD). However, long-term administration of L-DOPA can induce abnormal side effects. On the other hand, selective serotonin reuptake inhibitors (SSRIs) including fluoxetine have gained tremendous popularity in the...
journal_title:Journal of pharmacological sciences
pub_type: 杂志文章
doi:10.1254/jphs.12003fp
更新日期:2012-01-01 00:00:00
abstract::Type 2 diabetes (T2D) and obesity are important public health problems. The global prevalence of diabetes mellitus is 8.8%. Interventional diabetology and obesitology have been recently advocated as treatment options for T2D and obesity. The roles of metabolic surgery such as Roux-en-Y gastric bypass, sleeve gastrecto...
journal_title:Journal of pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.jphs.2017.01.001
更新日期:2017-02-01 00:00:00
abstract::Synaptic transmission is conducted by neurotransmitters released from nerve terminals. Neurotransmitter release is regulated both positively and negatively by multiple mechanisms, and its regulation is believed to be one of the important mechanisms of synaptic plasticity underlying learning and memory. Various protein...
journal_title:Journal of pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1254/jphs.93.41
更新日期:2003-09-01 00:00:00
abstract::A number of patients with hyperlipidemia are prescribed 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors that are concomitantly used along with the treatment of diabetes mellitus. The effects of atorvastatin and pravastatin on insulin-induced glucose uptake and the related signal transduction in 3T3L1 adipocytes we...
journal_title:Journal of pharmacological sciences
pub_type: 杂志文章
doi:10.1254/jphs.fp0072403
更新日期:2008-05-01 00:00:00
abstract::The G protein-coupled receptors (GPCRs) form the largest and the most versatile superfamily that share a seven-transmembrane-spanning architecture. GPCR-signaling is involved in vision, taste, olfaction, sympathetic/parasympathetic nervous functions, metabolism, and immune regulation, indicating that GPCRs are extreme...
journal_title:Journal of pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1254/jphs.14R13CP
更新日期:2014-01-01 00:00:00
abstract::Peroxisome proliferator-activated receptor gamma (PPARgamma) is a ligand-dependent transcriptional factor implicated in regulating adipogenesis, glucose homeostasis, and in mediating the action of the insulin sensitizing anti-diabetic thiazolidinedione (TZD) compounds. [3-(2,4-Dichlorobenzyl)-2-methyl-N-(pentylsulfony...
journal_title:Journal of pharmacological sciences
pub_type: 杂志文章
doi:10.1254/jphs.fp0050578
更新日期:2005-12-01 00:00:00
abstract::This study investigated the effects of thiol and heme oxidants on responsiveness to cGMP generators in isolated rat aorta and pulmonary artery using an organ chamber. The nitric oxide (NO) donor sodium nitroprusside (SNP)-induced relaxation was impaired by exposure to the thiol oxidant diamide in both the aorta and th...
journal_title:Journal of pharmacological sciences
pub_type: 杂志文章
doi:10.1016/j.jphs.2019.04.002
更新日期:2019-05-01 00:00:00
abstract::The aim of this study was to compare the effect of antimuscarinic antagonists on carbachol-induced contraction of normal human bladder and detrusor overactivity associated with benign prostatic hyperplasia (DO/BPH). Samples of human bladder muscle were obtained from patients undergoing total cystectomy for bladder can...
journal_title:Journal of pharmacological sciences
pub_type: 杂志文章
doi:10.1016/j.jphs.2015.05.005
更新日期:2015-06-01 00:00:00
abstract::MicroRNAs (miRNAs) are a group of small noncoding RNAs that regulate translational repression of multiple target mRNAs. The miRNAs in a whole cell regulate greater than 30% of all protein-coding genes. The vast majority of presently identified miRNAs are expressed in the brain in a spatially and temporally controlled ...
journal_title:Journal of pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1254/jphs.10r11fm
更新日期:2010-01-01 00:00:00
abstract::Baicalin from Scutellaria baicalensis is a major flavonoid constituent found in the traditional Chinese medicinal herb Baikal skull cap. It has been widely used for the treatment of various diseases such as pneumonia, diarrhea, and hepatitis. Recent studies have demonstrated that baicalin possesses a wide range of pha...
journal_title:Journal of pharmacological sciences
pub_type: 杂志文章
doi:10.1254/jphs.12200fp
更新日期:2013-01-01 00:00:00
abstract::This study investigated endogenous mediators involved in mosquito allergy-associated itching in mice. An intradermal injection of an extract of mosquito salivary gland elicited marked scratching in sensitized mice. The 5-lipoxygenase inhibitor zileuton (100 mg/kg), the 5-lipoxygenase activating peptide inhibitor MK-88...
journal_title:Journal of pharmacological sciences
pub_type: 杂志文章
doi:10.1254/jphs.fp0070404
更新日期:2007-09-01 00:00:00
abstract::GbaSM-4 cells, vascular smooth muscle cells (VSMCs) derived from brain basilar arteries, were shown to migrate toward d-nicotine by augmenting the actin cytoskeleton in their cell bodies and lamellipodia, and expression of nicotinic acetylcholine receptor (alpha7-nAChR) was detected in GbaSM-4 cells. Their chemotaxis ...
journal_title:Journal of pharmacological sciences
pub_type: 杂志文章
doi:10.1254/jphs.94.334
更新日期:2004-03-01 00:00:00
abstract::Cimetidine is known to suppress the growth of several tumors, including gastrointestinal cancer, in humans and animals. Nonetheless, whether other histamine H(2)-receptor antagonists exert such tumor suppressive effects remains unclear. The effect of roxatidine acetate hydrochloride (roxatidine), an H(2)-receptor anta...
journal_title:Journal of pharmacological sciences
pub_type: 杂志文章
doi:10.1254/jphs.93.321
更新日期:2003-11-01 00:00:00
abstract::The pharmacological mechanisms of a synthetic compound 1-benzyl-3-(5'-hydroxymethyl-2'-furyl) indazole (YC-1) in preventing smooth muscle cell proliferation remains to be elucidated. The present study was aimed to explore the effects of YC-1 on certain molecules responsible for cell proliferation, including transformi...
journal_title:Journal of pharmacological sciences
pub_type: 杂志文章
doi:10.1254/jphs.94.252
更新日期:2004-03-01 00:00:00
abstract::We have reported that the differentiation-inducing factors (DIFs) DIF-1 and DIF-3, morphogens secreted from Dictyostelium discoideum, inhibit proliferation of several cancer cells via suppression of the Wnt/beta-catenin signaling pathway. However, the target molecules of DIFs involved in the anti-proliferative effects...
journal_title:Journal of pharmacological sciences
pub_type: 杂志文章
doi:10.1254/jphs.09348fp
更新日期:2010-01-01 00:00:00
abstract::Tumor necrosis factor-alpha (TNFalpha)-induced cell death is regulated through the release of arachidonic acid (AA) by group IVA cytosolic phospholipase A2 (cPLA2alpha) in the murine fibroblast cell line L929. However, the signaling pathway by which TNFalpha activates cPLA2alpha remained to be solved. We examined AA r...
journal_title:Journal of pharmacological sciences
pub_type: 杂志文章
doi:10.1254/jphs.fpj04033x
更新日期:2004-11-01 00:00:00
abstract::We recently reported that physiological concentrations of 17beta-estradiol partially down-regulate cardiac rapidly-activating delayed rectifier K(+) currents (hERG currents) independently of estrogen-receptor signaling. To determine if other estrogens have the same effect as that of 17beta-estradiol, we investigated r...
journal_title:Journal of pharmacological sciences
pub_type: 杂志文章
doi:10.1254/jphs.08257sc
更新日期:2009-01-01 00:00:00