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Biomedical subjects

Iichiro Shimomura

Publications and source records attributed to Iichiro Shimomura.

At least 19 recordsLinked to original sources
PubMed2006

Effects of peroxisome proliferator-activated receptor ligands, bezafibrate and fenofibrate, on adiponectin level.

OBJECTIVE: Adiponectin is adipose-specific secretory protein and acts as anti-diabetic and anti-atherosclerotic molecule. We previously found peroxisome proliferators response element in adiponectin promoter region, suggesting that peroxisome proliferator-activated receptor (PPAR) ligands elevate adiponectin. Fibrates are known to be PPARalpha ligands and were shown to reduce risks of diabetes and cardiovascular disease. Effect of fibrates on adiponectin has not been clarified, whereas thiazolidinediones enhance adiponectin. Thus, we explored the possibility and mechanism that fibrates enhance adiponectin in humans, mice, and cells. METHODS AND RESULTS: Significant increase of serum adiponectin was observed in bezafibrate-treated subjects compared with placebo group in patients enrolled in The Bezafibrate Infarction Prevention study. Higher baseline adiponectin levels were strongly associated with reduced risk of new diabetes. Fibrates, bezafibrate and fenofibrate, significantly elevated adiponectin levels in wild-type mice and 3T3-L1 adipocytes. Such an effect was not observed in PPARalpha-deficient mice and adipocytes. Fibrates activated adiponectin promoter but failed to enhance its activity when the point mutation occurred in peroxisome proliferators response element site and the endogenous PPARalpha was knocked down by PPARalpha-RNAi. CONCLUSIONS: Our results suggest that fibrates enhance adiponectin partly through adipose PPARalpha and measurement of adiponectin might be a useful tool for searching subjects at high risk for diabetes.

Adipocytes↗
PubMed2006

Association of adiponectin and resistin with cardiovascular events in Korean patients with type 2 diabetes: the Korean atherosclerosis study (KAS): a 42-month prospective study.

Adiponectin and resistin are proteins that affect insulin resistance and atherosclerosis significantly. We investigated adiponectin and resistin concentrations as predictors of cardiovascular events in Korean patients with type 2 diabetes. The study in 2001 comprised 343 unrelated patients with type 2 diabetes (65+/-9.2 years old). They were followed up for 42 months. The baseline duration of diabetes, smoking status and history of cardiovascular diseases (CVD) were recorded. BMI, blood pressures, HbA1c, lipid profiles, ECG, creatinine and urine microalbumin were measured. Adiponectin and resistin were measured using enzyme-linked immunosorbent assays. The primary endpoint was defined as one of cardiovascular death, myocardial infarct, CABG, stroke, unstable angina or overt nephropathy. Thirty-eight patients (11.1%) experienced primary endpoint during the follow-up. After adjustment for age, sex, BMI, blood pressure and lipid status, participants in the lowest quartile of adiponectin levels compared with the highest had significantly increased risk of primary endpoint (relative risk=3.03; 95% CI 1.09-8.41; p=0.034). In contrast, resistin level had no influence on the risk of primary endpoint. A low level of adiponectin, not resistin, was a significant risk factor for the development of cardiovascular events in these Korean patients with type 2 diabetes.

Adiponectin↗
PubMed2006

Angiopoietin-like protein3 regulates plasma HDL cholesterol through suppression of endothelial lipase.

OBJECTIVE: A low level of high-density lipoprotein (HDL) in plasma has been recognized as an aspect of metabolic syndrome and as a crucial risk factor of cardiovascular events. However, the physiological regulation of plasma HDL levels has not been completely defined. Current studies aim to reveal the contribution of angiopoietin-like protein3 (angptl3), previously known as a plasma suppressor of lipoprotein lipase, to HDL metabolism. METHODS AND RESULTS: Angptl3-deficient mice showed low plasma HDL cholesterol and HDL phospholipid (PL), and which were increased by ANGPTL3 supplementation via adenovirus. In vitro, ANGPTL3 inhibited the phospholipase activity of endothelial lipase (EL), which hydrolyzes HDL-PL and hence decreases plasma HDL levels, through a putative heparin-binding site in the N-terminal domain of ANGPTL3. Post-heparin plasma in Angptl3-knockout mice had higher phospholipase activity than did that in wild-type mice, suggesting that the activity of endogenous EL is elevated in Angptl3-deficient mice. Furthermore, we established an ELISA system for human ANGPTL3 and found that plasma ANGPTL3 levels significantly correlated with plasma HDL cholesterol and HDL-PL levels in human subjects. CONCLUSIONS: Angptl3 acts as an inhibitor of EL and may be involved in the regulation of plasma HDL cholesterol and HDL-PL levels in humans and rodents.

Angiopoietin-Like Protein 3↗
PubMed2006

Increased lipid rafts and accelerated lipopolysaccharide-induced tumor necrosis factor-alpha secretion in Abca1-deficient macrophages.

Lipid rafts on the cell surface are believed to be very important as platforms for various cellular functions. The aim of this study was to know whether defective lipid efflux may influence lipid rafts on the cell surface and their related cellular functions. We investigated macrophages with defective lipid efflux from ATP binding cassette transporter A1-deficient (Abca1-KO) mice. Lipid rafts were evaluated by the following two novel probes: a biotinylated and protease (subtilisin Carlsberg)-nicked derivative of theta-toxin and a fluorescein ester of polyethylene glycol-derived cholesterol. Lipid rafts in Abca1-KO macrophages were increased, as demonstrated by both probes. Moreover, activities of nuclear factor kappaB, mRNA and intracellular distribution, and secretion of tumor necrosis factor-alpha (TNF-alpha) were examined after stimulation by lipopolysaccharides (LPSs). LPS-induced responses of the activation of nuclear factor kappaB and TNF-alpha were more prompt and accelerated in the Abca1-KO macrophages compared with wild-type macrophages. Modification of lipid rafts by cyclodextrin and nystatin corrected the abnormal response, suggesting an association between the increased lipid rafts and abnormal TNF-alpha secretion. We report here that Abca1-KO macrophages with defective lipid efflux exhibited increased lipid rafts on the cell surface and accelerated TNF-alpha secretion.

ATP Binding Cassette Transporter 1↗
PubMed2006

Neogenesis and proliferation of beta-cells induced by human betacellulin gene transduction via retrograde pancreatic duct injection of an adenovirus vector.

Betacellulin (BTC) has been shown to have a role in the differentiation and proliferation of beta-cells both in vitro and in vivo. We administered a human betacellulin (hBTC) adenovirus vector to male ICR mice via retrograde pancreatic duct injection. As a control, we administered a beta-galactosidase adenovirus vector. In the mice, hBTC protein was mainly overexpressed by pancreatic duct cells. On immunohistochemical analysis, we observed features of beta-cell neogenesis as newly formed insulin-positive cells in the duct cell lining or islet-like cell clusters (ICCs) closely associated with the ducts. The BrdU labeling index of beta-cells was also increased by the betacellulin vector compared with that of control mice. These results indicate that hBTC gene transduction into adult pancreatic duct cells promoted beta-cell differentiation (mainly from duct cells) and proliferation of pre-existing beta-cells, resulting in an increase of the beta-cell mass that improved glucose tolerance in diabetic mice.

Adenoviridae↗
PubMed2006

Adiponectin concentration in umbilical cord serum is positively associated with the weight ratio of fetus to placenta.

CONTEXT: Adiponectin (APN) concentration in umbilical cord serum is higher than that in adult serum. Except for the positive association between birth weight and cord APN concentration, little is known about the pathophysiological function of APN in fetal development. OBJECTIVE: The objective of this study was to evaluate the relationship of cord serum APN and IGF-I concentrations with the development of the fetoplacental unit. DESIGN AND METHODS: Umbilical cord serum APN and IGF-I concentrations were measured in term singleton deliveries (n = 94). The association of cord APN and IGF-I concentrations was evaluated in relation to fetal weight, placental weight, and fetoplacental (F/P) weight ratio. RESULTS: Mean concentrations and sd of APN and IGF-I were 36.1 +/- 14.0 microg/ml and 58.6 +/- 27.0 ng/ml, respectively. Cord APN concentration was positively associated with F/P weight ratio (r = 0.375, P < 0.001) as well as fetal weight (r = 0.389, P < 0.001) but not placental weight. Cord IGF-I concentration was positively associated with fetal weight (r = 0.405, P < 0.001) and placental weight (r = 0.400, P < 0.001) but not F/P weight ratio. In multiregression analysis, only APN concentration resulted in a significant determinant of F/P weight ratio among variables (beta = 0.376, P < 0.001). CONCLUSIONS: In cord hyperadiponectinemia, fetuses tend to be disproportionately larger for their placental weight and vice versa in cord hypoadiponectinemia. APN is shown to be the first biomarker positively associated with F/P weight ratio.

Adiponectin↗
PubMed2006

Visfatin in adipocytes is upregulated by hypoxia through HIF1alpha-dependent mechanism.

Obesity is associated with metabolic disorders, such as insulin resistance. Visfatin is an adipose-derived secretory factor to exert insulin-mimetic effects. Plasma visfatin levels and mRNA levels of visfatin in adipose tissues are increased in obesity. However, the mechanism that mediates induction of visfatin mRNA in adipose tissue of obesity remains unknown. Recent studies have reported that fat tissue is hypoxia in obesity. In this study, we investigated the effects of hypoxia on mRNA expression of visfatin in adipocytes. Hypoxia increased visfatin mRNA expression. Desferoxamine and Cobaltous chloride, two hypoxia mimetic compounds, also increased visfatin mRNA levels. Dimethyloxallyl glycine, a stabilizer of hypoxia-inducible factor 1alpha (HIF1alpha), mimicked the hypoxia-mediated upregulation of visfatin, and YC1, an inhibitor of HIF1 cancelled the hypoxia-induced upregulation of visfatin mRNA. We identified two functional hypoxia responsive elements (HRE) in mouse visfatin promoter. Hypoxic treatment and overexpression of HIF1alpha increased the promoter activity, and mutation of the HRE blunted hypoxia-induced activation of visfatin promoter. Our results suggest that visfatin mRNA expression is upregulated in the fat tissue of obesity through the activation of HIF1alpha pathway due to hypoxia.

3T3-L1 Cells↗
PubMed2006

Expression and prognostic role of RhoA GTPases in hepatocellular carcinoma.

The Rho sub-family of proteins is involved in regulating the organization of the cytoskeleton and in cell motility. Our aim is to clarify the clinical significance of Rho protein in hepatocellular carcinomas (HCC) and to determine the relationship between the level of expression and patient outcome following hepatectomy. The expression of RhoA protein in HCC and corresponding non-tumor tissues of 26 patients who underwent surgical resection was analyzed by immunoblotting. The expression level of each case was calculated as tumor/non-tumor (T/N) ratios. High expression (T/N> or =1) of RhoA protein in HCC compared to the paired non-tumor tissues was recognized in 18 patients (69.2%) of 26 samples. The activity of RhoA is also increased in HCC with high expression of RhoA. The high expression of RhoA protein did not correlate with various clinical parameters. However, the disease-free survival rates of the RhoA-high expression group (T/N> or =1) were significantly lower than those of the RhoA-low expression group (T/N<1) (P<0.05). The high expression of RhoA protein in HCC plays an important role in intrahepatic recurrence of patients who underwent a hepatectomy for HCC, and RhoA is a useful marker for predicting early recurrence in an early-stage HCC.

Adult↗
PubMed2006

Adiponectin deficiency exacerbates lipopolysaccharide/D-galactosamine-induced liver injury in mice.

AIM: To examine the effects of adiponectin on the functions of Kupffer cells, key modulators of lipopolysaccharide (LPS) -induced liver injury. METHODS: D-galactosamine (GalN) and LPS were injected intraperitoneally into adiponectin-/- mice and wild type mice. Kupffer cells, isolated from Sprague-Dawley rats, were preincubated with or without adiponectin, and then treated with LPS. RESULTS: In knockout mice, GalN/LPS injection significantly lowered the survival rate, significantly raised the plasma levels of alanine transaminase and tumor necrosis factor-alpha (TNF-alpha) and significantly reduced IL-10 levels compared with wild type mice. TNF-alpha gene expression in the liver was which higher and those of IL-10 were lower in knockout mice than in wild type mice. In cultured adiponectin-pre-treated Kupffer cells, LPS significantly lowered TNF-alpha levels and raised IL-10 levels in the culture media and their respective gene expression levels, compared with Kupffer cells without adiponectin-pre-treatment. CONCLUSION: Adiponectin supresses TNF-alpha production and induces IL-10 production by Kupffer cells in response to LPS stimulation, and a lack of adiponectin enhances LPS-induced liver injury.

Adiponectin↗
PubMed2006

Adiponectin replenishment ameliorates obesity-related hypertension.

Patients with obesity are susceptible to hypertension. We have reported that the plasma adiponectin levels are decreased in obesity and that adiponectin has many defensive properties against obesity-related diseases, such as type 2 diabetes and coronary artery disease. The aim of this study was to determine the relationship between adiponectin and hypertension in mice. We measured blood pressure and heart rate directly by a catheter in the carotid artery and indirectly by automatic sphygmomanometer at the tail artery. Obese KKAy mice had significantly lower plasma adiponectin levels and higher systolic blood pressure than control C57BL/6J mice at 21 weeks of age. Adenovirus-delivered adiponectin significantly decreased blood pressure in KKAy mice. The direct role of adiponectin on blood pressure regulation under insulin resistance-free state was investigated in adiponectin-knockout (KO) mice. Adiponectin KO mice developed hypertension when maintained on a high-salt diet (8% NaCl) without insulin resistance. The hypertension of salt-fed adiponectin KO mice was associated with reduced mRNA levels of endothelial NO synthase (eNOS) and prostaglandin I(2) synthase in aorta and low metabolite levels of endothelial NO synthase and prostaglandin I(2) synthase in plasma. Adiponectin therapy lowered the elevated blood pressure and corrected the above mRNA levels to those of the wild type. Our results suggest that hypoadiponectinemia contributes to the development of obesity-related hypertension, at least in part, directly, in addition to its effect via insulin resistance, and that adiponectin therapy can be potentially useful for hypertension in patients with the metabolic syndrome.

Adenoviridae↗
PubMed2006

High expression of leptin receptor mRNA in breast cancer tissue predicts poor prognosis for patients with high, but not low, serum leptin levels.

The association of mRNA expression levels of leptin receptors (long isoform: Lep-R(L) and short isoform: Lep-R(S)) in breast cancer tissue with patient prognosis was studied with special reference to the serum leptin level or the leptin mRNA level in tumor tissue. Lep-R(L), Lep-R(S) and leptin mRNA levels in breast cancer tissue (n = 91) were determined with a real-time PCR assay, and serum leptin levels in breast cancer patients (n = 67) with an enzyme-linked immunosorbent assay. Neither Lep-R(L) nor Lep-R(S) mRNA levels in tumor tissue were significantly associated with patient prognosis, but both intratumoral Lep-R(L) and Lep-R(S) mRNA high tumors were significantly (p < 0.01) associated with a poor prognosis. Multivariate analysis showed that a high level of both Lep-R (L) and Lep-R (S) mRNA in tumor tissue was a significant risk factor, independent of other risk factors. The subset analysis demonstrated that both intratumoral Lep-R(L) and Lep-R(S) mRNA high tumors were significantly associated with a poor prognosis for the subset of patients with high serum leptin or high intratumoral leptin mRNA levels but not in the subset of patients with low serum leptin or low intratumoral leptin mRNA levels. The association between both intratumoral Lep-R(L) and Lep-R(S) mRNA high tumors and a poor prognosis in the presence of high serum leptin or high intratumoral leptin mRNA levels seems to suggest that the leptin and Lep-R(L)/Lep-R(S) pathways are implicated in the growth stimulation of breast tumors. The well-established finding that obesity serves as a risk factor for relapse in breast cancer patients may thus be partially explained by the high serum leptin level seen in obese women.

Adult↗
PubMed2006

Effect of adiponectin on murine colitis induced by dextran sulfate sodium.

BACKGROUND & AIMS: Adiponectin, an adipose tissue-derived hormone, exhibits anti-inflammatory properties and has various biological functions, such as increasing insulin sensitivity, reducing hypertension, and suppressing atherosclerosis, liver fibrosis, and tumor growth. The aim of the present study was to determine the effect of adiponectin on intestinal inflammation. METHODS: We investigated the effect of adiponectin on dextran sulfate sodium (DSS)-induced colitis by using adiponectin-knockout (APN-KO) mice and an adenovirus-mediated adiponectin expression system. We also examined the contribution of adiponectin deficiency to trinitrobenzene sulfonic acid (TNBS)-induced colitis. In vitro, we examined the effect of adiponectin on intestinal epithelial cells. RESULTS: After administration of 0.5% DSS for 15 days, APN-KO mice developed much more severe colitis compared with wild-type mice. The messenger RNA expression levels of chemokines were significantly higher in the colonic tissues of DSS-treated APN-KO mice compared with wild-type mice, accompanied by increased cellular infiltration, including macrophages. Adenovirus-mediated supplementation of adiponectin significantly attenuated the severity of colitis, but there were no differences in the severity of TNBS-induced colitis between the 2 groups. Adiponectin receptors were expressed in intestinal epithelial cells, and adiponectin inhibited lipopolysaccharide-induced interleukin-8 production in intestinal epithelial cells. CONCLUSIONS: Adiponectin is protective against DSS-induced murine colitis, probably due to the inhibition of chemokine production in intestinal epithelial cells and the following inflammatory responses, including infiltration of macrophages and release of proinflammatory cytokines.

Adiponectin↗
PubMed2006

Systemic oxidative stress is associated with visceral fat accumulation and the metabolic syndrome.

BACKGROUND: The metabolic syndrome (MetS) is a major target for prevention of atherosclerotic cardiovascular diseases and visceral fat accumulation is an underlying component of MetS. The aim of this study was to investigate the association of systemic oxidative stress with visceral fat accumulation and MetS. METHODS AND RESULTS: The study group consisted of Japanese men (n=44; 51.2+/-11.4 years) and women (n=61; 55.4 +/-13.4 years). Urinary 8-epi-prostaglandin F2alpha (8-epi-PGF2 alpha) concentration, a biomarker of systemic oxidative stress, was significantly high in the subjects with MetS. As the urinary concentration of 8-epi-PGF2alpha increased, the number of criteria for MetS were significantly met (abdominal obesity, hypertriglyceridemia, low high-density lipoprotein-cholesterol, hypertension, and high fasting glucose). Among parameters associated with MetS, the correlation coefficient of visceral fat area (VFA) with urinary 8-epi-PGF2alpha concentration was the highest (r=0.636, p<0.0001). In non-obese subjects, the correlation coefficient of VFA with urinary 8-epi-PGF2alpha concentration was higher (r=0.728, p<0.0001), although there was no significant correlation between subcutaneous fat area and urinary 8-epi-PGF2 alpha. Stepwise multiple regression analysis identified VFA as the strongest and independent determinant of urinary 8-epi-PGF2 alpha (p<0.0001) followed by adiponectin (p=0.0212) and, high sensitive C-reactive protein (p=0.0365). CONCLUSIONS: Systemic oxidative stress, as measured by urinary 8-epi-PGF2alpha , is strongly associated with visceral fat accumulation and MetS.

Adiponectin↗
PubMed2006

Associations of adiponectin levels with incident impaired glucose metabolism and type 2 diabetes in older men and women: the hoorn study.

OBJECTIVE: Adiponectin is an adipose tissue-derived protein. Low levels are associated with obesity, insulin resistance, and type 2 diabetes. Our objective was to investigate the prospective association between adiponectin levels and the 6.4-year risk of type 2 diabetes and of impaired glucose metabolism (IGM). RESEARCH DESIGN AND METHODS: The Hoorn Study is a cohort study among Caucasians, aged 50-75 years. BMI, waist-to-hip ratio (WHR), fasting glucose, 2-h glucose, triglycerides, HDL cholesterol, LDL cholesterol, alanine aminotransferase, leptin, and adiponectin were measured at baseline. Lifestyle (alcohol intake, smoking, and physical activity) was assessed by questionnaires. After a mean follow-up of 6.4 years, glucose tolerance was assessed by a 75-g oral glucose tolerance test. Analyses were performed in 1,264 subjects (584 men and 680 women) without type 2 diabetes at baseline. For analyses of incident IGM, 239 subjects with IGM at baseline and/or type 2 diabetes at follow-up were excluded. RESULTS: Age- and lifestyle-adjusted odds ratios and 95% CIs comparing highest with lowest adiponectin quartile were 0.52 (0.23-1.18) in men and 0.15 (0.06-0.39) in women for type 2 diabetes and 0.90 (0.51-1.61) and 0.28 (0.16-0.48) for IGM, respectively. The risks were only slightly reduced after adjustment for WHR and leptin as markers of (abdominal) adiposity. Adjustment for baseline fasting and postload glucose levels (potential mediators) substantially diminished these inverse associations with type 2 diabetes (0.79 [0.32-1.91] and 0.62 [0.21-1.81]) and with IGM (1.20 [0.61-2.35] and 0.48 [0.26-0.90]), respectively. CONCLUSIONS: A high adiponectin level was strongly associated with a lower risk of IGM and type 2 diabetes, particularly in women. These results suggest that adiponectin is involved in the pathophysiology linking obesity to type 2 diabetes.

Adiponectin↗
PubMed2006

[The effects of visceral fat accumulation by diabetes mellitus on bone metabolism].

The number of obesity and diabetes mellitus in the world has been rapidly increasing in population. Current lifestyle initiates obesity, especially visceral fat accumulation, and leads to the onset of metabolic syndrome, such as cardiovascular events, hyperlipidemia and diabetes mellitus, based on insulin resistance. Several studies of adipocyte function have revealed that adipose tissue is not merely an energy-storing organ but it secretes a variety of biologically active molecules, conceptualized as "adipocytokines", including tumor necrosis factor-alpha, estrogen, leptin and adiponectin and that abnormal secretion of these adipocytokines causes metabolic syndrome. Adipocytes exist not only in the visceral and subcutaneous tissue but also in the bone marrow. Therefore, it is important to know their effects not only on glucose and lipid metabolism but also on bone metabolism. This report aims to review some of the effects of visceral fat accumulation by diabetes mellitus on bone metabolism.

Animals↗
PubMed2005

Hepatocyte nuclear factor-4alpha is essential for glucose-stimulated insulin secretion by pancreatic beta-cells.

Mutations in the hepatocyte nuclear factor (HNF)-4alpha gene cause a form of maturity-onset diabetes of the young (MODY1) that is characterized by impairment of glucose-stimulated insulin secretion by pancreatic beta-cells. HNF-4alpha, a transcription factor belonging to the nuclear receptor superfamily, is expressed in pancreatic islets as well as in the liver, kidney, and intestine. However, the role of HNF-4alpha in pancreatic beta-cell is unclear. To clarify the role of HNF-4alpha in beta-cells, we generated beta-cell-specific HNF-4alpha knock-out (betaHNF-4alphaKO) mice using the Cre-LoxP system. The betaHNF-4alphaKO mice exhibited impairment of glucose-stimulated insulin secretion, which is a characteristic of MODY1. Pancreatic islet morphology, beta-cell mass, and insulin content were normal in the HNF-4alpha mutant mice. Insulin secretion by betaHNF-4alphaKO islets and the intracellular calcium response were impaired after stimulation by glucose or sulfonylurea but were normal after stimulation with KCl or arginine. Both NAD(P)H generation and ATP content at high glucose concentrations were normal in the betaHNF-4alphaKO mice. Expression levels of Kir6.2 and SUR1 proteins in the betaHNF-4alphaKO mice were unchanged as compared with control mice. Patch clamp experiments revealed that the current density was significantly increased in betaHNF-4alphaKO mice compared with control mice. These results are suggestive of the dysfunction of K(ATP) channel activity in the pancreatic beta-cells of HNF-4alpha-deficient mice. Because the K(ATP) channel is important for proper insulin secretion in beta-cells, altered K(ATP) channel activity could be related to the impaired insulin secretion in the betaHNF-4alphaKO mice.

ATP-Binding Cassette Transporters↗
PubMed2005

Selective allosteric ligand activation of the retinoid X receptor heterodimers of NGFI-B and Nurr1.

NGFI-B, an orphan member of the NR4A subfamily of the nuclear receptors, recognizes specific sequences in the promoters of neuronal target genes as a monomer. Although NGFI-B also forms a heterodimer with the retinoid X receptor (RXR), a receptor for 9-cis retinoic acid (9CRA), endogenous targets of the heterodimer have not been identified. We investigated the role of RXR ligand binding in NGFI-B/RXR activation and found that dibenzodiazepine-derived ligands, such as the weak RXR agonist HX600, selectively activate NGFI-B/RXR heterodimers. HX600 also activated the heterodimer formed by RXR and Nurr1, another NR4A subfamily receptor. In an assembly assay that detects ligand-dependent reconstruction of the ligand-binding domain, HX600 and not 9CRA induced an allosteric ligand effect on NGFI-B through RXRalpha binding. The data indicate that the RXR heterodimers of NGFI-B and Nurr1 are selectively activated by the RXR ligand HX600, and that compounds such as HX600 will be valuable tools in investigating NGFI-B and Nurr1 function.

Allosteric Site↗