The Experts below are selected from a list of 297 Experts worldwide ranked by ideXlab platform
Liming Yu - One of the best experts on this subject based on the ideXlab platform.
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melatonin rescues cardiac thioredoxin system during ischemia reperfusion injury in acute hyperglycemic state by restoring notch1 hes1 akt signaling in a Membrane Receptor dependent manner
Journal of Pineal Research, 2017Co-Authors: Liming Yu, Guolong Zhao, Yang Yang, Zhi Li, Jian Zhang, Yinli Xu, Huishan WangAbstract:Stress hyperglycemia is commonly observed in patients suffering from ischemic heart disease. It not only worsens cardiovascular prognosis but also attenuates the efficacies of various cardioprotective agents. This study aimed to investigate the protective effect of melatonin against myocardial ischemia-reperfusion (MI/R) injury in acute hyperglycemic state with a focus on Notch1/Hes1/Akt signaling and intracellular thioredoxin (Trx) system. Sprague-Dawley rats were subjected to MI/R surgery and high glucose (HG, 500 g/L) infusion (4 ml/kg/h) to induce temporary hyperglycemia. Rats were treated with or without melatonin (10 mg/kg/d) during the operation. Furthermore, HG (33mM) incubated H9c2 cardiomyoblasts were treated in the presence or absence of Luzindole (a competitive melatonin Receptor antagonist), DAPT (a γ-Secretase inhibitor), LY294002 (a PI3-kinase/Akt inhibitor) or thioredoxin-interacting protein (Txnip) adenoviral vectors. We found that acute hyperglycemia aggravated MI/R injury by suppressing Notch1/Hes1/Akt signaling and intracellular Trx activity. Melatonin treatment effectively ameliorated MI/R injury by reducing infarct size, myocardial apoptosis and oxidative stress. Moreover, melatonin also markedly enhanced Notch1/Hes1/Akt signaling and rescued intracellular Trx system by up-regulating Notch1, N1ICD, Hes1 and p-Akt expressions, increasing Trx activity and down-regulated Txnip expression. However, these effects were blunted by Luzindole, DAPT or LY294002. Additionally, Txnip overexpression not only decreased Trx activity, but also attenuated the cytoprotective effect of melatonin. We conclude that impaired Notch1 signaling aggravates MI/R injury in acute hyperglycemic state. Melatonin rescues Trx system by reducing Txnip expression via Notch1/Hes1/Akt signaling in a Membrane Receptor-dependent manner. Its role as a prophylactic/therapeutic drug deserves further clinical study. This article is protected by copyright. All rights reserved.
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Membrane Receptor dependent notch1 hes1 activation by melatonin protects against myocardial ischemia reperfusion injury in vivo and in vitro studies
Journal of Pineal Research, 2015Co-Authors: Liming Yu, Hongliang Liang, Zhihong Lu, Guolong Zhao, Mengen Zhai, Yang Yang, Jian Yang, Dinghua Yi, Wensheng Chen, Xiaowu WangAbstract:Melatonin confers profound protective effect against myocardial ischemia-reperfusion injury (MI/RI). Activation of Notch1/Hairy and enhancer of split 1 (Hes1) signaling also ameliorates MI/RI. We hypothesize that melatonin attenuates MI/RI-induced oxidative damage by activating Notch1/Hes1 signaling pathway with phosphatase and tensin homolog deleted on chromosome 10 (Pten)/Akt acting as the downstream signaling pathway in a melatonin Membrane Receptor-dependent manner. Male Sprague Dawley rats were treated with melatonin (10 mg/kg/day) for 4 wk and then subjected to MI/R surgery. Melatonin significantly improved cardiac function and decreased myocardial apoptosis and oxidative damage. Furthermore, in cultured H9C2 cardiomyocytes, melatonin (100 μmol/L) attenuated simulated ischemia-reperfusion (SIR)-induced myocardial apoptosis and oxidative damage. Both in vivo and in vitro study demonstrated that melatonin treatment increased Notch1, Notch1 intracellular domain (NICD), Hes1, Bcl-2 expressions, and p-Akt/Akt ratio and decreased Pten, Bax, and caspase-3 expressions. However, these protective effects conferred by melatonin were blocked by DAPT (the specific inhibitor of Notch1 signaling), luzindole (the antagonist of melatonin Membrane Receptors), Notch1 siRNA, or Hes1 siRNA administration. In summary, our study demonstrates that melatonin treatment protects against MI/RI by modulating Notch1/Hes1 signaling in a Receptor-dependent manner and Pten/Akt signaling pathways are key downstream mediators.
Yang Yang - One of the best experts on this subject based on the ideXlab platform.
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melatonin rescues cardiac thioredoxin system during ischemia reperfusion injury in acute hyperglycemic state by restoring notch1 hes1 akt signaling in a Membrane Receptor dependent manner
Journal of Pineal Research, 2017Co-Authors: Liming Yu, Guolong Zhao, Yang Yang, Zhi Li, Jian Zhang, Yinli Xu, Huishan WangAbstract:Stress hyperglycemia is commonly observed in patients suffering from ischemic heart disease. It not only worsens cardiovascular prognosis but also attenuates the efficacies of various cardioprotective agents. This study aimed to investigate the protective effect of melatonin against myocardial ischemia-reperfusion (MI/R) injury in acute hyperglycemic state with a focus on Notch1/Hes1/Akt signaling and intracellular thioredoxin (Trx) system. Sprague-Dawley rats were subjected to MI/R surgery and high glucose (HG, 500 g/L) infusion (4 ml/kg/h) to induce temporary hyperglycemia. Rats were treated with or without melatonin (10 mg/kg/d) during the operation. Furthermore, HG (33mM) incubated H9c2 cardiomyoblasts were treated in the presence or absence of Luzindole (a competitive melatonin Receptor antagonist), DAPT (a γ-Secretase inhibitor), LY294002 (a PI3-kinase/Akt inhibitor) or thioredoxin-interacting protein (Txnip) adenoviral vectors. We found that acute hyperglycemia aggravated MI/R injury by suppressing Notch1/Hes1/Akt signaling and intracellular Trx activity. Melatonin treatment effectively ameliorated MI/R injury by reducing infarct size, myocardial apoptosis and oxidative stress. Moreover, melatonin also markedly enhanced Notch1/Hes1/Akt signaling and rescued intracellular Trx system by up-regulating Notch1, N1ICD, Hes1 and p-Akt expressions, increasing Trx activity and down-regulated Txnip expression. However, these effects were blunted by Luzindole, DAPT or LY294002. Additionally, Txnip overexpression not only decreased Trx activity, but also attenuated the cytoprotective effect of melatonin. We conclude that impaired Notch1 signaling aggravates MI/R injury in acute hyperglycemic state. Melatonin rescues Trx system by reducing Txnip expression via Notch1/Hes1/Akt signaling in a Membrane Receptor-dependent manner. Its role as a prophylactic/therapeutic drug deserves further clinical study. This article is protected by copyright. All rights reserved.
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Membrane Receptor dependent notch1 hes1 activation by melatonin protects against myocardial ischemia reperfusion injury in vivo and in vitro studies
Journal of Pineal Research, 2015Co-Authors: Liming Yu, Hongliang Liang, Zhihong Lu, Guolong Zhao, Mengen Zhai, Yang Yang, Jian Yang, Dinghua Yi, Wensheng Chen, Xiaowu WangAbstract:Melatonin confers profound protective effect against myocardial ischemia-reperfusion injury (MI/RI). Activation of Notch1/Hairy and enhancer of split 1 (Hes1) signaling also ameliorates MI/RI. We hypothesize that melatonin attenuates MI/RI-induced oxidative damage by activating Notch1/Hes1 signaling pathway with phosphatase and tensin homolog deleted on chromosome 10 (Pten)/Akt acting as the downstream signaling pathway in a melatonin Membrane Receptor-dependent manner. Male Sprague Dawley rats were treated with melatonin (10 mg/kg/day) for 4 wk and then subjected to MI/R surgery. Melatonin significantly improved cardiac function and decreased myocardial apoptosis and oxidative damage. Furthermore, in cultured H9C2 cardiomyocytes, melatonin (100 μmol/L) attenuated simulated ischemia-reperfusion (SIR)-induced myocardial apoptosis and oxidative damage. Both in vivo and in vitro study demonstrated that melatonin treatment increased Notch1, Notch1 intracellular domain (NICD), Hes1, Bcl-2 expressions, and p-Akt/Akt ratio and decreased Pten, Bax, and caspase-3 expressions. However, these protective effects conferred by melatonin were blocked by DAPT (the specific inhibitor of Notch1 signaling), luzindole (the antagonist of melatonin Membrane Receptors), Notch1 siRNA, or Hes1 siRNA administration. In summary, our study demonstrates that melatonin treatment protects against MI/RI by modulating Notch1/Hes1 signaling in a Receptor-dependent manner and Pten/Akt signaling pathways are key downstream mediators.
Nicoletta Fortunati - One of the best experts on this subject based on the ideXlab platform.
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The additionally glycosylated variant of human sex hormone-binding globulin (SHBG) is linked to estrogen-dependence of breast cancer
Breast Cancer Research and Treatment, 1999Co-Authors: Marzia Becchis, Piero Sismondi, Annamaria Fazzari, Sabrina Ondei, Alda Alfarano, Claudio Coluccia, Nicoletta Biglia, Roberto Frairia, Patrizia Ferrera, Nicoletta FortunatiAbstract:Sex Hormone-Binding Globulin (SHBG), the plasma carrier for androgens and estradiol, inhibits the estradiol-induced proliferation of breast cancer cells through its Membrane Receptor, cAMP, and PKA. In addition, the SHBG Membrane Receptor is preferentially expressed in estrogen-dependent (ER+/PR+) breast cancers which are also characterized by a lower proliferative rate than tumors negative for the SHBG Receptor. A variant SHBG with a point mutation in exon 8, causing an aminoacid substitution (Asp 327-->Asn) and thus, the introduction of an additional N-glycosylation site, has been reported. In this work, the distribution of the SHBG variant was studied in 255 breast cancer patients, 32 benign mammary disease patients, and 120 healthy women. The presence of the SHBG mutation was evaluated with PCR amplification of SHBG exon 8 and Hinf I restriction fragment length polymorphism (RFLP) procedure. This technique allowed us to identify 54 SHBG variants (53 W/v and 1 v/v) in breast cancer patients (21.2%), 5 variants (4 W/v and 1 v/v) in benign mammary disease patients (15.6%), and 14 variants (W/v) in the control group (11.6%). The results of PCR and RFLP were confirmed both by nucleotide sequence of SHBG exon 8 and western blot of the plasma SHBG. No differences in the mean plasma level of the protein were observed in the three populations. The frequency of the SHBG variant was significantly higher in ER+/PR+ tumors and in tumors diagnosed in patients over 50 years of age than in the control group. This observation suggests the existence of a close link between the estrogen-dependence of breast cancer and the additionally glycosylated SHBG, further supporting a critical role of the protein in the neoplasm.
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The Membrane Receptor for sex steroid binding protein is not ubiquitous
Journal of Endocrinological Investigation, 1992Co-Authors: Roberto Frairia, Annamaria Fazzari, Nicoletta Fortunati, Federica Fissore, P. Zeppegno, L. Varvello, M. Orsello, Laura BertaAbstract:The tissue distribution of the Membrane Receptor for the Sex Steroid Binding Protein (SBP) has been studied, either in estrogen/androgen dependent tissues and in tissues not strictly sex steroid dependent. A specific interaction of SBP with cell mem-branes has been observed to occur only in estro gen/androgen dependent tissues, some of them had been previously shown by our laboratory and by other authors to possess a specific Receptor for the protein. Thus, the sex steroid dependence of the tissue is likely to be determinant for the expression of the Membrane Receptor for Sex Steroid Binding Protein.
Jing Dong - One of the best experts on this subject based on the ideXlab platform.
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identity of an estrogen Membrane Receptor coupled to a g protein in human breast cancer cells
Endocrinology, 2005Co-Authors: Peter Thomas, Yefei Pang, Edward J Filardo, Jing DongAbstract:Although nonclassical estrogen actions initiated at the cell surface have been described in many tissues, the identities of the Membrane estrogen Receptors (mERs) mediating these actions remain unclear. Here we show that GPR30, an orphan Receptor unrelated to nuclear estrogen Receptors, has all the binding and signaling characteristics of a mER. A high-affinity (dissociation constant 2.7 nm), limited capacity, displaceable, single binding site specific for estrogens was detected in plasma Membranes of SKBR3 breast cancer cells that express GPR30 but lack nuclear estrogen Receptors. Progesterone-induced increases and small interfering RNA-induced decreases in GPR30 expression in SKBR3 cells were accompanied by parallel changes in specific estradiol-17β (E2) binding. Plasma Membranes of human embryonic kidney 293 cells transfected with GPR30, but not those of untransfected cells, and human placental tissues that express GPR30 also displayed high-affinity, specific estrogen binding typical of mERs. E2 treatm...
Xiaowu Wang - One of the best experts on this subject based on the ideXlab platform.
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Membrane Receptor dependent notch1 hes1 activation by melatonin protects against myocardial ischemia reperfusion injury in vivo and in vitro studies
Journal of Pineal Research, 2015Co-Authors: Liming Yu, Hongliang Liang, Zhihong Lu, Guolong Zhao, Mengen Zhai, Yang Yang, Jian Yang, Dinghua Yi, Wensheng Chen, Xiaowu WangAbstract:Melatonin confers profound protective effect against myocardial ischemia-reperfusion injury (MI/RI). Activation of Notch1/Hairy and enhancer of split 1 (Hes1) signaling also ameliorates MI/RI. We hypothesize that melatonin attenuates MI/RI-induced oxidative damage by activating Notch1/Hes1 signaling pathway with phosphatase and tensin homolog deleted on chromosome 10 (Pten)/Akt acting as the downstream signaling pathway in a melatonin Membrane Receptor-dependent manner. Male Sprague Dawley rats were treated with melatonin (10 mg/kg/day) for 4 wk and then subjected to MI/R surgery. Melatonin significantly improved cardiac function and decreased myocardial apoptosis and oxidative damage. Furthermore, in cultured H9C2 cardiomyocytes, melatonin (100 μmol/L) attenuated simulated ischemia-reperfusion (SIR)-induced myocardial apoptosis and oxidative damage. Both in vivo and in vitro study demonstrated that melatonin treatment increased Notch1, Notch1 intracellular domain (NICD), Hes1, Bcl-2 expressions, and p-Akt/Akt ratio and decreased Pten, Bax, and caspase-3 expressions. However, these protective effects conferred by melatonin were blocked by DAPT (the specific inhibitor of Notch1 signaling), luzindole (the antagonist of melatonin Membrane Receptors), Notch1 siRNA, or Hes1 siRNA administration. In summary, our study demonstrates that melatonin treatment protects against MI/RI by modulating Notch1/Hes1 signaling in a Receptor-dependent manner and Pten/Akt signaling pathways are key downstream mediators.
