Effects of Deep Optic Nerve Head Structures on Bruch's Membrane Opening- Minimum Rim Width and Peripapillary Retinal Nerve Fiber Layer.

Purpose: To explore the effects of deep optic nerve head (ONH) structures on Bruch's membrane opening (BMO)-minimum rim width (MRW) and peripapillary retinal nerve fiber layer thickness (pRNFLT) in healthy eyes.

Design: Prospective cross-sectional study.

Methods: Two hundred five healthy eyes of 141 subjects (mean ± standard deviation of age and axial length (AXL): 46.

Association of Bergmeister Papilla and Deep Optic Nerve Head Structures With Prelaminar Schisis of Normal and Glaucomatous Eyes.

Purpose: To investigate factors associated with the severity of prelaminar schisis (PLS) in heathy subjects and glaucoma patients.

Design: Prospective cross-sectional study.

Methods: A total of 217 eyes of 217 subjects (110 normal eyes and 107 open angle glaucoma eyes) were studied.

Deep Optic Nerve Head Structures Associated With Increasing Axial Length in Healthy Myopic Eyes of Moderate Axial Length.

Purpose: To elucidate which swept-source optical coherence tomography (OCT)-derived optic nerve head (ONH) parameters are associated with longer axial length (AXL) in healthy myopic eyes.

Design: Prospective cross-sectional observational study.

Methods: Two hundred eleven healthy eyes of 140 participants (96 emmetropic-mild myopic [AXL: 22.

Liver X receptor α is involved in the transcriptional regulation of the 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase gene.

The activity of 6-phosphofructo-1-kinase is strictly controlled by fructose-2,6-bisphosphate, the level of which is regulated by another enzyme, 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFK2/FBP2). PFK2/FBP2 is a bifunctional enzyme, having kinase and phosphatase activities, and regulates both glycolysis and gluconeogenesis. Here, we examined the hormonal regulation of the PFK2/FBP2 gene in vitro using the reporter assay, the electromobility shift assay (EMSA), and the chromatin immunoprecipitation (ChIP) assay in HuH7 cells and also using the mouse liver in vivo.

Involvement of GCMB in the transcriptional regulation of the human parathyroid hormone gene in a parathyroid-derived cell line PT-r: effects of calcium and 1,25(OH)2D3.

Expression of the PTH gene is known to be under strict tissue-specific control and is also regulated by extracellular calcium and 1,25(OH)(2)D. However, the precise mode of transcriptional regulation remains to be elucidated, because of the unavailability of appropriate cell lines derived from the parathyroid gland. We tried to identify the transcription factor(s) regulating the human PTH gene transcription using the PT-r cell line.

Glucocorticoid receptor-beta and receptor-gamma exert dominant negative effect on gene repression but not on gene induction.

Glucocorticoid has diverse biological effects through induction or repression of its target genes via glucocorticoid receptor (GR). In addition to the wild-type GR (GR-alpha), a variety of GR variants has been reported, and these are thought to modify glucocorticoid action. Among others, GR-beta is reported be responsible for the glucocorticoid resistance frequently observed in steroid-resistant nephrotic syndrome, rheumatoid arthritis, and hematologic tumors, although the precise molecular mechanism remains unclear.

PPARbeta/delta regulates the human SIRT1 gene transcription via Sp1.

NAD-dependent deacetylase SIRT1 is known to be activated by caloric restriction and is related to longevity. A natural polyphenolic compound resveratrol is also shown to increases SIRT1 activity and extends lifespan. However, the transcriptional regulation of SIRT1 gene has not completely examined in the context of metabolism.

Hormonal regulation of acetyl-CoA carboxylase isoenzyme gene transcription.

Both glucocorticoid and insulin are known to have an anabolic effect on lipogenesis. Acetyl-CoA, an intermediate product of glycolysis, is supplied for fatty acid synthesis when carbohydrate intake is sufficient. Acetyl-CoA carboxylase (ACC), consisting of two isoenzymes ACC1 and ACC2, mediates the conversion from acetyl-CoA to malonyl-CoA, and thus plays a key role for the regulation of lipogenesis.

Hormonal regulation of glycolytic enzyme gene and pyruvate dehydrogenase kinase/phosphatase gene transcription.

Both glucocorticoid and insulin are known to have an anabolic effect on lipogenesis. The glycolytic pathway is a part of the lipogenic pathway in the liver, and glycolytic enzymes mediate the conversion from glucose to pyruvate, and pyruvate dehydrogenase complex (PDC) mediates the conversion from pyruvate to acetyl-CoA, the activity of which is regulated by pyruvate dehydrogenase kinases (PDKs) and phosphatases (PDPs). In this study, we surveyed the effects of glucocorticoid, insulin, and forskolin (used as a surrogate of glucagon) on the transcriptional activity of glucokinase (GK), phosphofructokinase-1 (PFK1), liver-type pyruvate kinase (LPK), and all the PDKs/PDPs isoform genes.

Plasma adiponectin levels are increased despite insulin resistance in corticotropin-releasing hormone transgenic mice, an animal model of Cushing syndrome.

Adiponectin (AdN), an adipokine derived from the adipose tissue, has an insulin-sensitizing effect, and plasma AdN is shown to be decreased in obesity and/or insulin resistant state. To clarify whether changes in AdN are also responsible for the development of glucocorticoid-induced insulin resistance, we examined AdN concentration in plasma and AdN expression in the adipose tissue, using corticotropin-releasing hormone (CRH) transgenic mouse (CRH-Tg), an animal model of Cushing syndrome. We found, unexpectedly, that plasma AdN levels in CRHTg were significantly higher than those in wild-type littermates (wild-type: 19.

Glucocorticoid receptor plays an indispensable role in mineralocorticoid receptor-dependent transcription in GR-deficient BE(2)C and T84 cells in vitro.

The mineralocorticoid receptor (MR) plays an important functional role in the central nervous system; however, the molecular mechanism of MR-dependent gene expression is not entirely clear. In this study, we examined the MR-dependent transcriptional regulation using a human neuronal cell line BE(2)C and an MR/GR-dependent reporter gene (HRE-luciferase) in vitro. Western blot analysis revealed that the cell line expresses MR but not glucocorticoid receptor (GR).

Relative abundance of Delta(5)-sterols in plasma membrane lipids of root-tip cells correlates with aluminum tolerance of rice.

We investigated variations in aluminum (Al) tolerance among rice plants, using ancestor cultivars from the family line of the Al-tolerant and widely cultivated Japonica cultivar, Sasanishiki. The cultivar Rikuu-20 was Al sensitive, whereas a closely related cultivar that is a descendant of Rikuu-20, Rikuu-132, was Al tolerant. These two cultivars were compared to determine mechanisms underlying variations in Al tolerance.

Insulin exhibits short-term anti-inflammatory but long-term proinflammatory effects in vitro.

Although insulin is indispensable for maintaining glucose homeostasis, it is still controversial whether or not a high concentration of insulin is deleterious. We examined the effect of insulin on the transcriptional activity of NF-kappaB, which mediates the expression of a variety of inflammation/coagulation-related genes using hepatocyte cell lines in vitro. We found that insulin (1 nM) alone caused minimal increase in NF-kappaB-mediated transcription.

Differential regulation of 11beta-hydroxysteroid dehydrogenase type-1 and -2 gene transcription by proinflammatory cytokines in vascular smooth muscle cells.

Glucocorticoid hormone is activated by 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD-1) mainly in glucocorticoid-target organs such as the liver and the anterior corticotroph cells, and inactivated by type 2 (11beta-HSD-2) in mineralocorticoid-target cells such as renal and colonic epithelial cells. In this study, we examined the expression and action of these glucocorticoid-metabolizing enzymes in the A10 rat aortic smooth muscle cells (VSMC) in vitro. We found that both 11beta-HSD-1 and -2 mRNAs as well as glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) were expressed in the cells.

Insulin enhancement of cytokine-induced coagulation/inflammation-related gene transcription in hepatocytes.

Hyperinsulinemia is a known risk factor for cardiovascular events, but its molecular basis is not completely understood. In this study, we examined the effects of insulin alone, or insulin and proinflammatory cytokines, on the expression of inflammation/coagulation-related genes in hepatocytes. We found that, in the HepG2 human hepatocyte cell line, insulin stimulated the transcriptional activity of plasminogen activator inhibitor 1 (PAI-1), fibrinogen-gamma and C-reactive protein (CRP) genes in time- and dose-dependent manners.

Multisignal regulation of the rat NMDA1 receptor subunit gene--a pivotal role of glucocorticoid-dependent transcription.

Although excess of glucocorticoid causes neuronal damage with cognitive disorders, the molecular mechanism for this remains unclear. In this study, we examined the effect of adrenal corticosteroids on the transcription of NMDA glutamate receptor subunit genes and Alzheimer disease-related genes such as amyloid precursor protein (APP), beta-site amyloid precursor protein-cleaving enzyme 1 (BACE1), and presenilin using neuronal cell lines in vitro. We found that synthetic glucocorticoid dexamethasone (dex) potently increased the promoter activity of NMDA1 and 2A subunit genes, but did not stimulate those of Alzheimer disease-related genes.

Lipopolysaccharide stimulates proopiomelanocortin gene expression in AtT20 corticotroph cells.

While lipopolysaccharides (LPS) are known to activate the hypothalamo-pituitary-adrenal axis, their direct effects on proopiomelanocortin (POMC) and adrenocorticotropin (ACTH) expression at the pituitary level through Toll-like receptors (TLRs) remain unclear. In this study, we examined the effects of LPS on ACTH secretion and the transcription of the POMC gene in the AtT20 mouse pituitary corticotroph cell line. RT-PCR analysis showed that TLR1-4 and 6 subtype mRNAs were expressed in AtT20 cells.

Is the metabolic syndrome an intracellular Cushing state? Effects of multiple humoral factors on the transcriptional activity of the hepatic glucocorticoid-activating enzyme (11beta-hydroxysteroid dehydrogenase type 1) gene.

Although glucocorticoid, as "gluco-" literally implies, plays an important role in maintaining the blood glucose level, excess of glucocorticoid production/action is known to cause impaired glucose tolerance and diabetes. Since 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1), which converts inactive cortisone to active cortisol, is primarily expressed in the liver, an enhanced expression of the enzyme may increase the intracellular glucocorticoid level and thus increase the hepatic glucose production. In this study, we examined the effects of multiple humoral factors related to the metabolic syndrome on the transcriptional activity of 11beta-HSD1 gene in hepatocytes in vitro.

Predominant role of 25OHD in the negative regulation of PTH expression: clinical relevance for hypovitaminosis D.

Although severe deficiency of bioactive vitamin D (1,25OH2D) causes rickets, mild insufficiency of the hormone, known as hypovitaminosis D, is responsible for the occurrence of secondary hyperparathyroidism and osteoporosis. To clarify the pathophysiology of the disease, we studied the negative feedback effect of 1,25OH2D and its precursor 25OHD on the transcriptional activity of parathyroid hormone (PTH) gene using the PT-r parathyroid cell line. We found that PT-r cells express endogenous 1alpha-hydroxylase as well as PTH mRNAs.

Activation of AMP-activated protein kinase stimulates proopiomelanocortin gene transcription in AtT20 corticotroph cells.

Starvation is known to activate the hypothalamo-pituitary-adrenal (HPA) axis, a representative antistress system in the living organism. In this study, we investigated in vitro whether activation of the AMP-activated protein kinase (AMPK), which is known to occur in intracellular energy depletion, influences the expression of POMC gene that encodes adrenocorticotropin. We first confirmed that each subunit of AMPK was expressed in the AtT20 corticotroph cell line.

High glucose alone, as well as in combination with proinflammatory cytokines, stimulates nuclear factor kappa-B-mediated transcription in hepatocytes in vitro.

Diabetes mellitus is frequently associated with coagulation disorders such as coronary heart disease and stroke. We aimed to clarify the molecular mechanism whereby hyperglycemia causes the procoagulant state. HuH7 human hepatocyte cells were treated with high glucose alone or in combination with proinflammatory cytokines, and the effects on the activity of the transcription factor nuclear factor kappa-B (NF-kappaB), which mediates the expression of acute-phase and coagulation-related genes, were examined.

Molecular mechanisms for corticotropin-releasing hormone gene repression by glucocorticoid in BE(2)C neuronal cell line.

The molecular mechanisms for the suppression of corticotropin-releasing hormone (CRH) gene expression by glucocorticoid remain to be clarified albeit the well-known physiological role of the glucocorticoid-induced negative feedback regulation of the gene. In this study, we examined the effect of glucocorticoid on CRH gene transcription using the human BE(2)C neuronal cell line, which expresses the CRH gene and produces CRH peptide intrinsically. Dexamethasone, a specific ligand for the glucocorticoid receptor (GR), potently suppressed human CRH 5'-promoter activity.

High glucose activates pituitary proopiomelanocortin gene expression: possible role of free radical-sensitive transcription factors.

Background: Hyperglycemia is recognized as a metabolic stress, and indeed it is known to stimulate hypothalamo-pituitary-adrenal (HPA) axis, a representative anti-stress system, in patients with diabetes mellitus or in animal models of hyperglycemia. Thus, we tried to clarify the molecular mechanism of glucose-induced HPA axis activation.

Methods: We studied the effect of high glucose on the transcriptional regulation of proopiomelanocortin (POMC) gene that encodes adrenocorticotropic hormone, a central mediator of HPA axis, using AtT20 corticotroph cell line in vitro.