Univocal identification of retinal ganglion cells(RGCs) is an essential prerequisite for studying their degeneration and neuroprotection. Before the advent of phenotypic markers, RGCs were normally identified using re...Univocal identification of retinal ganglion cells(RGCs) is an essential prerequisite for studying their degeneration and neuroprotection. Before the advent of phenotypic markers, RGCs were normally identified using retrograde tracing of retinorecipient areas. This is an invasive technique, and its use is precluded in higher mammals such as monkeys. In the past decade, several RGC markers have been described. Here, we reviewed and analyzed the specificity of nine markers used to identify all or most RGCs, i.e., pan-RGC markers, in rats, mice, and macaques. The best markers in the three species in terms of specificity, proportion of RGCs labeled, and indicators of viability were BRN3A, expressed by vision-forming RGCs, and RBPMS, expressed by vision-and non-vision-forming RGCs. NEUN, often used to identify RGCs, was expressed by non-RGCs in the ganglion cell layer, and therefore was not RGC-specific. γ-SYN, TUJ1, and NF-L labeled the RGC axons, which impaired the detection of their somas in the central retina but would be good for studying RGC morphology. In rats, TUJ1 and NF-L were also expressed by non-RGCs. BM88, ERRβ,and PGP9.5 are rarely used as markers, but they identified most RGCs in the rats and macaques and ERRβ in mice. However, PGP9.5 was also expressed by non-RGCs in rats and macaques and BM88 and ERRβ were not suitable markers of viability.展开更多
Estrogen-related receptor alpha （ERRα） plays an important role in the development of hor- monezdependent cancers, but its roles in lung cancer remain elusive. The present study was aimed to investigate the effects ...Estrogen-related receptor alpha （ERRα） plays an important role in the development of hor- monezdependent cancers, but its roles in lung cancer remain elusive. The present study was aimed to investigate the effects of ERRα on the proliferation and metastasis of lung cancer A549 cells. The mRNA and protein levels of ERRor were detected in lung cancer A549 and MCF-7 cells and bronchial epithelial BEAS-2B cells by qRT-PCR and Western blotting, respectively. ERRor plasmid transfection and XCT-790 （an inverse agonist of ERRc0 were used to up-regulate or down-regulate ERRα expression in A549 cells, respectively. The viability of A549 cells was measured by cell counting kit-8 （CCK-8） and the motility of A549 cells by wound healing assay and Transwell migration/invasion assay. The epithelial markers E-cadherin （E-Cad） and zona occludin-1 （ZO-1）, the mesenchymal markers fi- bronectin （FN） and vimentin （Vim） and the transcription factors （Snail, Zebl Twist and Slug） were fur- ther detected at mRNA and protein levels by qRT-PCR and Western blotting, respectively. The results showed that ERRor promoted the growth of lung cancer A549 cells in vitro. XCT-790 significantly in- hibited the migration and invasion of A549 cells. Over-expression of ERRα promoted the epithe- lial-to-mesenchymal transition （EMT） of A549 ceils, down-regulated the epithelial makers E-Cad and ZO-1, and up-regulated the mesenchymal makers FN and Vim. Silencing of Slug, but not other tran- scription factors, significantly abolished the ERRs-induced EMT of A549 cells. It was suggested that ERRor promoted the migration and invasion of A549 cells by inducing EMT, and Slug was involved in the process. Targeting ERRor might be an efficient approach for lung cancer treatment.展开更多
Environmental chemicals in drinking water can impact human health through nuclear receptors. Additionally, estrogen-related receptors （ERRs） are vulnerable to endocrine-disrupting effects. To date, however, ERR disr...Environmental chemicals in drinking water can impact human health through nuclear receptors. Additionally, estrogen-related receptors （ERRs） are vulnerable to endocrine-disrupting effects. To date, however, ERR disruption of drinking water potency has not been reported. We used ERRy two-hybrid yeast assay to screen ERRy disrupting activities in a drinking water treatment plant （DWTP） located in north China and in source water from a reservoir, focusing on agonistic, antagonistic, and inverse agonistie activity to 4-hydroxytamoxifen （4-OHT）. Water treatment processes in the DWTP consisted of pre-chlorination, coagulation, coal and sand filtration, activated carbon filtration, and secondary chlorination processes. Samples were extracted by solid phase extraction. Results showed that ERRγ antagonistic activities were found in all sample extracts, but agonistic and inverse agonistic activity to 4-OHT was not found. When calibrated with the toxic equivalent of 4-OHT, antagonistic effluent effects ranged from 3.4 to 33.1 μg/L. In the treatment processes, secondary chlorination was effective in removing ERRy antagonists, but the coagulation process led to significantly increased ERRy antagonistic activity. The drinking water treatment processes removed 73.5 % of ERRy antagonists. To our knowledge, the occurrence of ERRy disruption activities on source and drinking water in vitro had not been reported previously. It is vital, therefore, to increase our understanding of ERRγ disrupting activities in drinking water.展开更多
Objective Previous study suggested that estradiol(E2)plays an important role in otolith shedding by regulating the expression of otoconin 90(OC90).The purpose of this article is to provide further data on the effect a...Objective Previous study suggested that estradiol(E2)plays an important role in otolith shedding by regulating the expression of otoconin 90(OC90).The purpose of this article is to provide further data on the effect and mechanism of E2 on the morphology of otolith.Methods The rats receiving bilateral ovariectomy(OVX)were used as animal models.Co-immunoprecipitation was used to observe the relationship between estrogen receptor(ER)and estrogen-related receptorα(ERRα).The morphology of otolith was observed under the scanning electron microscopy.Western blotting and qPCR were used for quantitative analysis of the roles of ER and ERRαin regulating OC90 expression.Results The looser otoliths were observed in rats receiving bilateral OVX,which could be reversed by supplementation with E2.The level of ERRαwas decreased in bilateral OVX rats.ER and ERRαinteracted with each other on the regulation of the expression of OC90.Conclusion Our results suggest ER and ERRαare both important downstream receptors involved in regulating OC90 expression in utricles of rats,and ERRαprobably functions by interacting with ER.This provides evidence for the mechanism of otolith shedding.And it may be significant for future studies of targeted prevention and therapies for benign paroxysmal positional vertigo.展开更多
Estrogen-related receptor gamma(ERRg)is one of three members of the ERR family and remains an orphan,as there are no known natural ligands.ERRg is an inducible transcription factor,and its ligandindependent transcript...Estrogen-related receptor gamma(ERRg)is one of three members of the ERR family and remains an orphan,as there are no known natural ligands.ERRg is an inducible transcription factor,and its ligandindependent transcriptional activity is regulated by co-regulator interactions and post-transcriptional modifications.Recent findings from animal models show that ERRg,as a downstream mediator of multiple extracellular signals,plays a key role in coordinating endocrine and metabolic signals,resulting in changes in glucose,alcohol,lipid,and iron metabolism in the liver.Therefore,dysregulation of this receptor contributes to the pathogenesis of metabolic diseases such as hyperglycemia,insulin resistance,and alcoholic liver injury.Interestingly,ERRg is also involved in responses to bacterial infection.These findings establish the importance of ERRg in the endocrine and metabolic control of liver metabolism,and suggest that ERRg may be a promising therapeutic target for metabolic diseases of the liver.展开更多
The aim of the present study have been reported to review the estrogen level in the patients with the breast cancer and healthy individuals.Breast cancer is one of the most common diseases in women worldwide that is c...The aim of the present study have been reported to review the estrogen level in the patients with the breast cancer and healthy individuals.Breast cancer is one of the most common diseases in women worldwide that is characterized by uncontrolled growth of malignant cells in the mammary epithelial tissue.The estrogen was found at normal level in most patients with ER-positive breast cancer and in healthy individuals,while its high level was higher among patients with ER-negative breast cancer.Many studies show evidences about the role of estrogen at a high level on the development of breast cancer.The association between the estrogen levels and the presence of Candida spp.in vagina of patients with breast cancer was reviewed.展开更多
Vascular endothelial growth factor(VEGF)is associated with endothelial cell proliferation,migration and angiogenesis.Estrogen-related receptorγ(ERRγ)plays important regulatory roles in fatty acid oxidation,mitochond...Vascular endothelial growth factor(VEGF)is associated with endothelial cell proliferation,migration and angiogenesis.Estrogen-related receptorγ(ERRγ)plays important regulatory roles in fatty acid oxidation,mitochondrial biogenesis and gluconeogenesis.Recently,ERRγ has been shown to be involved in angiogenesis;however,the mechanism of ERRγ-mediated angiogenesis is poorly understood.Here the results show that ERRγactivates VEGF gene transcription via two putative estrogen-related receptor binding elements(ERREs)mapped to the promoter region.Chromatin immunoprecipitation assays confirmed that ERRγ binds to the identified ERREs.Adenovirus-mediated overexpression of ERRγ increased the expression of VEGF gene and induced an increase in VEGF secretion in C2C12 myotubes.In contrast,the secretion of VEGF was significantly decreased in the presence of the ERRγ inverse agonist GSK5182.Furthermore,treatment of human umbilical vein endothelial cells(HUVECs)with the conditioned medium from ERRγ-overexpressing C2C12 myotubes significantly increased proliferation,migration and tube formation.These data indicate that VEGF functions as a downstream target gene of ERRγ and mediates the effects of ERRγ on endothelial cells proliferation,migration and angiogenesis.This physiological function of ERRγ might provide a novel target for treatment of ischemic diseases.展开更多
In order to explore the functions of retinol binding protein (RBP4) in regulation of gene expression, yeast two hybrid assay and transient co-transforming were used to detect the interactions between RBP4 and nuclear ...In order to explore the functions of retinol binding protein (RBP4) in regulation of gene expression, yeast two hybrid assay and transient co-transforming were used to detect the interactions between RBP4 and nuclear receptors and the effects of over-expressed RBP4 on trans-activation functions of human estrogen receptor related receptor 1 (hERR1) and human estrogen (hER). The requirement of activation function domain-2 (AF-2) for hER to interact with RBP4 was also detected by the yeast two hybrid assay. The results show that RBP4 could interact with many nuclear receptors including mouse estrogen receptor related receptor 3 (mERR3), retinoid X receptor (RXR), glucocorticoid receptor (GR), progestin receptor (PR), and androgen receptor (AR) in yeast cells. Over-expressed RBP4 could strongly enhance the trans-activation functions of hERR1 and hER in a dose-dependent manner, respectively. RBP4 could also interact with hER in an AF-2-dependent manner.展开更多
基金supported by the Spanish Ministry of Economy and Competitiveness(PID2019-106498GB-I0)Instituto de Salud Carlos III,Fondo Europeo de Desarrollo Regional“Una manera de hacer Europa”(PI19/00071)+2 种基金Fundación Séneca,Agencia de Ciencia y Tecnología Región de Murcia(19881/GERM/15)Spanish Ministry of Science and Innovation(PID 2019-106498 GB-I00)Intramural Research Program of the National Eye Institute,National Institutes of Health(NIH/NEI RO1 EY029087)。
文摘Univocal identification of retinal ganglion cells(RGCs) is an essential prerequisite for studying their degeneration and neuroprotection. Before the advent of phenotypic markers, RGCs were normally identified using retrograde tracing of retinorecipient areas. This is an invasive technique, and its use is precluded in higher mammals such as monkeys. In the past decade, several RGC markers have been described. Here, we reviewed and analyzed the specificity of nine markers used to identify all or most RGCs, i.e., pan-RGC markers, in rats, mice, and macaques. The best markers in the three species in terms of specificity, proportion of RGCs labeled, and indicators of viability were BRN3A, expressed by vision-forming RGCs, and RBPMS, expressed by vision-and non-vision-forming RGCs. NEUN, often used to identify RGCs, was expressed by non-RGCs in the ganglion cell layer, and therefore was not RGC-specific. γ-SYN, TUJ1, and NF-L labeled the RGC axons, which impaired the detection of their somas in the central retina but would be good for studying RGC morphology. In rats, TUJ1 and NF-L were also expressed by non-RGCs. BM88, ERRβ,and PGP9.5 are rarely used as markers, but they identified most RGCs in the rats and macaques and ERRβ in mice. However, PGP9.5 was also expressed by non-RGCs in rats and macaques and BM88 and ERRβ were not suitable markers of viability.
基金supported by the Fundamental Research Funds of the Central Universities(No.21613316)
文摘Estrogen-related receptor alpha （ERRα） plays an important role in the development of hor- monezdependent cancers, but its roles in lung cancer remain elusive. The present study was aimed to investigate the effects of ERRα on the proliferation and metastasis of lung cancer A549 cells. The mRNA and protein levels of ERRor were detected in lung cancer A549 and MCF-7 cells and bronchial epithelial BEAS-2B cells by qRT-PCR and Western blotting, respectively. ERRor plasmid transfection and XCT-790 （an inverse agonist of ERRc0 were used to up-regulate or down-regulate ERRα expression in A549 cells, respectively. The viability of A549 cells was measured by cell counting kit-8 （CCK-8） and the motility of A549 cells by wound healing assay and Transwell migration/invasion assay. The epithelial markers E-cadherin （E-Cad） and zona occludin-1 （ZO-1）, the mesenchymal markers fi- bronectin （FN） and vimentin （Vim） and the transcription factors （Snail, Zebl Twist and Slug） were fur- ther detected at mRNA and protein levels by qRT-PCR and Western blotting, respectively. The results showed that ERRor promoted the growth of lung cancer A549 cells in vitro. XCT-790 significantly in- hibited the migration and invasion of A549 cells. Over-expression of ERRα promoted the epithe- lial-to-mesenchymal transition （EMT） of A549 ceils, down-regulated the epithelial makers E-Cad and ZO-1, and up-regulated the mesenchymal makers FN and Vim. Silencing of Slug, but not other tran- scription factors, significantly abolished the ERRs-induced EMT of A549 cells. It was suggested that ERRor promoted the migration and invasion of A549 cells by inducing EMT, and Slug was involved in the process. Targeting ERRor might be an efficient approach for lung cancer treatment.
基金supported by the National High Technology Research and Development Program (863) of China(No. 2007AA06Z414)the National Natural Science Foundation of China(No. 50778170)
文摘Environmental chemicals in drinking water can impact human health through nuclear receptors. Additionally, estrogen-related receptors （ERRs） are vulnerable to endocrine-disrupting effects. To date, however, ERR disruption of drinking water potency has not been reported. We used ERRy two-hybrid yeast assay to screen ERRy disrupting activities in a drinking water treatment plant （DWTP） located in north China and in source water from a reservoir, focusing on agonistic, antagonistic, and inverse agonistie activity to 4-hydroxytamoxifen （4-OHT）. Water treatment processes in the DWTP consisted of pre-chlorination, coagulation, coal and sand filtration, activated carbon filtration, and secondary chlorination processes. Samples were extracted by solid phase extraction. Results showed that ERRγ antagonistic activities were found in all sample extracts, but agonistic and inverse agonistic activity to 4-OHT was not found. When calibrated with the toxic equivalent of 4-OHT, antagonistic effluent effects ranged from 3.4 to 33.1 μg/L. In the treatment processes, secondary chlorination was effective in removing ERRy antagonists, but the coagulation process led to significantly increased ERRy antagonistic activity. The drinking water treatment processes removed 73.5 % of ERRy antagonists. To our knowledge, the occurrence of ERRy disruption activities on source and drinking water in vitro had not been reported previously. It is vital, therefore, to increase our understanding of ERRγ disrupting activities in drinking water.
基金supported by grants from Scientific Research Plan Project of Science and Technology Commission of Shanghai Municipality(No.18ZR1439200)Talents Training Program of Pudong Hospital affiliated to Fudan University(No.PX201705).
文摘Objective Previous study suggested that estradiol(E2)plays an important role in otolith shedding by regulating the expression of otoconin 90(OC90).The purpose of this article is to provide further data on the effect and mechanism of E2 on the morphology of otolith.Methods The rats receiving bilateral ovariectomy(OVX)were used as animal models.Co-immunoprecipitation was used to observe the relationship between estrogen receptor(ER)and estrogen-related receptorα(ERRα).The morphology of otolith was observed under the scanning electron microscopy.Western blotting and qPCR were used for quantitative analysis of the roles of ER and ERRαin regulating OC90 expression.Results The looser otoliths were observed in rats receiving bilateral OVX,which could be reversed by supplementation with E2.The level of ERRαwas decreased in bilateral OVX rats.ER and ERRαinteracted with each other on the regulation of the expression of OC90.Conclusion Our results suggest ER and ERRαare both important downstream receptors involved in regulating OC90 expression in utricles of rats,and ERRαprobably functions by interacting with ER.This provides evidence for the mechanism of otolith shedding.And it may be significant for future studies of targeted prevention and therapies for benign paroxysmal positional vertigo.
基金This work was supported by National Creative Research Initiatives Grant(No.20110018305 to H.-S.Choi and National Research Foundation(NRF)No.2018R1D1A1B07043953 to D.-K.Kim)the NRF funded by the Korean government(Ministry of Science,ICT&Future Planning and Ministry of Education)also carried out with the support of“Cooperative Research Program for Agriculture Science and Technology Development(No.PJ01280701 to D.-K.Kim)”Rural Development Administration,Republic of Korea.
文摘Estrogen-related receptor gamma(ERRg)is one of three members of the ERR family and remains an orphan,as there are no known natural ligands.ERRg is an inducible transcription factor,and its ligandindependent transcriptional activity is regulated by co-regulator interactions and post-transcriptional modifications.Recent findings from animal models show that ERRg,as a downstream mediator of multiple extracellular signals,plays a key role in coordinating endocrine and metabolic signals,resulting in changes in glucose,alcohol,lipid,and iron metabolism in the liver.Therefore,dysregulation of this receptor contributes to the pathogenesis of metabolic diseases such as hyperglycemia,insulin resistance,and alcoholic liver injury.Interestingly,ERRg is also involved in responses to bacterial infection.These findings establish the importance of ERRg in the endocrine and metabolic control of liver metabolism,and suggest that ERRg may be a promising therapeutic target for metabolic diseases of the liver.
文摘The aim of the present study have been reported to review the estrogen level in the patients with the breast cancer and healthy individuals.Breast cancer is one of the most common diseases in women worldwide that is characterized by uncontrolled growth of malignant cells in the mammary epithelial tissue.The estrogen was found at normal level in most patients with ER-positive breast cancer and in healthy individuals,while its high level was higher among patients with ER-negative breast cancer.Many studies show evidences about the role of estrogen at a high level on the development of breast cancer.The association between the estrogen levels and the presence of Candida spp.in vagina of patients with breast cancer was reviewed.
基金supported by the Natural Science Foundation of Hubei Province of China(Grant No.2012FFB00302).
文摘Vascular endothelial growth factor(VEGF)is associated with endothelial cell proliferation,migration and angiogenesis.Estrogen-related receptorγ(ERRγ)plays important regulatory roles in fatty acid oxidation,mitochondrial biogenesis and gluconeogenesis.Recently,ERRγ has been shown to be involved in angiogenesis;however,the mechanism of ERRγ-mediated angiogenesis is poorly understood.Here the results show that ERRγactivates VEGF gene transcription via two putative estrogen-related receptor binding elements(ERREs)mapped to the promoter region.Chromatin immunoprecipitation assays confirmed that ERRγ binds to the identified ERREs.Adenovirus-mediated overexpression of ERRγ increased the expression of VEGF gene and induced an increase in VEGF secretion in C2C12 myotubes.In contrast,the secretion of VEGF was significantly decreased in the presence of the ERRγ inverse agonist GSK5182.Furthermore,treatment of human umbilical vein endothelial cells(HUVECs)with the conditioned medium from ERRγ-overexpressing C2C12 myotubes significantly increased proliferation,migration and tube formation.These data indicate that VEGF functions as a downstream target gene of ERRγ and mediates the effects of ERRγ on endothelial cells proliferation,migration and angiogenesis.This physiological function of ERRγ might provide a novel target for treatment of ischemic diseases.
文摘In order to explore the functions of retinol binding protein (RBP4) in regulation of gene expression, yeast two hybrid assay and transient co-transforming were used to detect the interactions between RBP4 and nuclear receptors and the effects of over-expressed RBP4 on trans-activation functions of human estrogen receptor related receptor 1 (hERR1) and human estrogen (hER). The requirement of activation function domain-2 (AF-2) for hER to interact with RBP4 was also detected by the yeast two hybrid assay. The results show that RBP4 could interact with many nuclear receptors including mouse estrogen receptor related receptor 3 (mERR3), retinoid X receptor (RXR), glucocorticoid receptor (GR), progestin receptor (PR), and androgen receptor (AR) in yeast cells. Over-expressed RBP4 could strongly enhance the trans-activation functions of hERR1 and hER in a dose-dependent manner, respectively. RBP4 could also interact with hER in an AF-2-dependent manner.
