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1
المؤلفون: Tao Zeng, Jeff Groth, Ruya Zhao, Xufeng Chen, Yulei Tao, Hailiang Hu, Jiaoti Huang, Enze Ma, Lingfan Xu, Chaozhao Liang
المصدر: Endocrine-Related Cancer. 26:59-71
مصطلحات موضوعية: Male, 0301 basic medicine, Mitochondrial ROS, Cancer Research, DNA repair, Endocrinology, Diabetes and Metabolism, Poly ADP ribose polymerase, Ataxia Telangiectasia Mutated Proteins, Synthetic lethality, Naphthalenes, urologic and male genital diseases, Article, Mice, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Cell Line, Tumor, Animals, Humans, Lactic Acid, Cell Proliferation, L-Lactate Dehydrogenase, Chemistry, Cell growth, Warburg effect, Prostatic Neoplasms, Castration-Resistant, Glucose, 030104 developmental biology, Oncology, Anaerobic glycolysis, 030220 oncology & carcinogenesis, PARP inhibitor, Disease Progression, Cancer research
الوصف: ATM is a well-known master regulator of double strand break (DSB) DNA repair and the defective DNA repair has been therapeutically exploited to develop PARP inhibitors based on the synthetic lethality strategy. ATM mutation is found with increased prevalence in advanced metastatic castration-resistant prostate cancer (mCRPC). However, the molecular mechanisms underlying ATM mutation-driving disease progression are still largely unknown. Here, we report that ATM mutation contributes to the CRPC progression through a metabolic rather than DNA repair mechanism. We showed that ATM deficiency generated by CRISPR/Cas9 editing promoted CRPC cell proliferation and xenograft tumor growth. ATM deficiency altered cellular metabolism and enhanced Warburg effect in CRPC cells. We demonstrated that ATM deficiency shunted the glucose flux to aerobic glycolysis by upregulating LDHA expression, which generated more lactate and produced less mitochondrial ROS to promote CRPC cell growth. Inhibition of LDHA by siRNA or inhibitor FX11 generated less lactate and accumulated more ROS in ATM-deficient CRPC cells and therefore potentiated the cell death of ATM-deficient CRPC cells. These findings suggest a new therapeutic strategy for ATM-mutant CRPC patients by targeting LDHA-mediated glycolysis metabolism, which might be effective for the PARP inhibitor resistant mCRPC tumors.
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7086abd2263f975628e634ac7756c20bTest
https://doi.org/10.1530/erc-18-0196Test -
2
المؤلفون: Ying Xing, Xi Zhang, Nana Zhang, Xiangyang Liu, Jingbo Lai, Hengxin Liu, Jie Ming
المصدر: Journal of Molecular Endocrinology. 58:167-177
مصطلحات موضوعية: Male, 0301 basic medicine, Angiogenesis, Phosphatidylinositol 3-Kinases, 0302 clinical medicine, Endocrinology, Enos, Malondialdehyde, Phosphorylation, Endothelial dysfunction, Cells, Cultured, Tube formation, biology, Caspase 3, Middle Aged, Netrin-1, Diabetic Foot, Vascular endothelial growth factor A, embryonic structures, Female, Signal Transduction, medicine.medical_specialty, animal structures, Nitric Oxide Synthase Type III, Cell Survival, Morpholines, Genetic Vectors, Neovascularization, Physiologic, Adenoviridae, 03 medical and health sciences, Internal medicine, Human Umbilical Vein Endothelial Cells, medicine, Humans, Viability assay, Molecular Biology, Protein kinase B, PI3K/AKT/mTOR pathway, omega-N-Methylarginine, L-Lactate Dehydrogenase, business.industry, fungi, medicine.disease, biology.organism_classification, Glucose, 030104 developmental biology, Diabetes Mellitus, Type 2, Gene Expression Regulation, Chromones, Case-Control Studies, business, Proto-Oncogene Proteins c-akt, 030217 neurology & neurosurgery
الوصف: Diabetic foot ulceration (DFU) represents a common vascular complication of diabetes mellitus (DM) with high morbidity and disability resulting from amputation. Netrin-1 level was decreased in type 2 DM patients and has been identified as a protective regulator against diabetes-triggered myocardial infarction and nephropathy. Unfortunately, its role and molecular mechanism in DFU remain poorly elucidated. Here, netrin-1 levels were reduced in DM and DFU patients relative to healthy controls, with netrin-1 levels being the lowest in DFU patients. Moreover, exposure to high glucose (HG) also suppressed netrin-1 expression in human umbilical vein endothelial cells (HUVECs). Elevated netrin-1 expression by infection with Ad-netrin-1 adenovirus vector protected against HUVEC injury in response to HG by ameliorating the inhibitory effects on cell viability, lactate dehydrogenase (LDH) and malondialdehyde (MDA) levels, cell apoptotic rate and caspase-3 activity. Importantly, HG-impaired angiogenesis was improved after netrin-1 overexpression by elevating cell migration, capillary-like tube formation and VEGF production. Mechanism assay substantiated that netrin-1 elevation increased the phosphorylation levels of AKT and eNOS, and NO production, which was notably suppressed by HG, indicating that netrin-1 overexpression restored HG-triggered impairment of the PI3K/AKT-eNOS pathway. More intriguingly, preconditioning with LY294002 (PI3K/AKT antagonist) or NG-monomethyl-l-arginine (eNOS inhibitor) antagonized netrin-1-induced activation of the PI3K/AKT-eNOS pathway. Concomitantly, treatment with these antagonists also attenuated the protective role of netrin-1 in endothelial dysfunction upon HG stimulation. These results suggest that elevation of netrin-1 may restore HG-triggered impairment of HUVEC and angiogenesis by activating the PI3K/AKT-eNOS pathway, indicating a potential agent for wound healing in DFU patients.
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8f6d30c227dcc419ddf466bb70e6a86dTest
https://doi.org/10.1530/jme-16-0239Test -
3
المصدر: Journal of Molecular Endocrinology. 55:219-229
مصطلحات موضوعية: medicine.medical_specialty, endocrine system diseases, Lactate dehydrogenase A, medicine.medical_treatment, Human Embryonic Stem Cells, Biology, Cell Line, Mice, Endocrinology, Insulin resistance, Pregnancy, Hyperinsulinism, Insulin-Secreting Cells, Diabetes mellitus, Internal medicine, medicine, Hyperinsulinemia, Animals, Humans, Insulin, education, 3' Untranslated Regions, Lactate Dehydrogenases, Molecular Biology, education.field_of_study, Binding Sites, Base Sequence, Reproduction, Endoderm, nutritional and metabolic diseases, Cell Differentiation, medicine.disease, Gestational diabetes, Transplantation, Diabetes, Gestational, Disease Models, Animal, MicroRNAs, Glucose, Gene Expression Regulation, Hyperglycemia, Body Composition, Female, RNA Interference, Pancreas Transplantation, Biomarkers
الوصف: Gestational diabetes mellitus (GDM) is a condition commonly encountered during mid to late pregnancy with pathologic manifestations including hyperglycemia, hyperinsulinemia, insulin resistance, and fetal mal-development. The deficit and dysfunction of insulin secreting β-cells are signature symptoms for GDM. Pancreatic progenitors derived from human embryonic stem cells (hESCs) were shown to be able to effectively treat diabetes in mice. In this study, we first identified that microRNA-410 (miR-410) directly targets lactate dehydrogenase A (LDHA), a gene selectively repressed in normal insulin secreting β-cells. hESCs that can be induced to express miR-410 hence keeping LDHA levels in check were then differentiatedin vitrointo pancreatic endoderm, followed by transplantation intodb/+mouse model of GDM. The transplant greatly improved glucose metabolism and reproductive outcome of the pregnant females suffering from GDM. Our findings describe for the first time the method of combining miRNA with hESCs, providing proof of concept by employing genetically modified stem cell therapy for treating GDM.
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7cd06074cebd705130bebffa0d7e9be6Test
https://doi.org/10.1530/jme-15-0100Test -
4
المؤلفون: Changdong Yan, Shoulei Kang, Dongye Li, Aiying Liu, Liping Gao, Chuanying Xu, Ying Liu, Hong Sun
المصدر: Journal of Endocrinology. 212:61-69
مصطلحات موضوعية: medicine.medical_specialty, Hormone Replacement Therapy, medicine.drug_class, Ovariectomy, Endocrinology, Diabetes and Metabolism, Adrenergic beta-Antagonists, Drug Evaluation, Preclinical, Apoptosis, Myocardial Reperfusion Injury, Propanolamines, Rats, Sprague-Dawley, chemistry.chemical_compound, Endocrinology, Internal medicine, Lactate dehydrogenase, Animals, Medicine, Myocytes, Cardiac, Testosterone, Cells, Cultured, Estradiol, L-Lactate Dehydrogenase, business.industry, Antagonist, medicine.disease, Androgen, ICI-118,551, Myocardial Contraction, Rats, Up-Regulation, Menopause, chemistry, Estrogen, Ovariectomized rat, Drug Therapy, Combination, Female, Receptors, Adrenergic, beta-2, business
الوصف: After menopause, the development of cardiovascular disease (CVD) is due not only to estrogen decline but also to androgen decline. This study examined the effects of either estradiol (E2) or testosterone replacement alone or E2–testosterone combination on isolated myocytes in ovariectomized (Ovx) rats subjected to ischemia/reperfusion (I/R). Furthermore, we determined whether the effects are associated with β2-adrenoceptor (β2-AR). Five groups of adult female Sprague–Dawley rats were used: Sham operation (Sham) rats, bilateral Ovx rats, Ovx rats with E240 μg/kg per day (Ovx+E), Ovx rats with testosterone 150 μg/kg per day (Ovx+T), and Ovx rats with E240 μg/kg per day+testosterone 150 μg/kg per day (Ovx+E/T). We determined the lactate dehydrogenase (LDH) release, percentage of rod-shaped cells and apoptosis of ventricular myocytes from rats of all groups subjected to I/R. Then, we determined the above indices and contractile function with or without a selective β2-AR antagonist ICI 118 551. We also determined the expression of β2-AR. Our data show that either E2or testosterone replacement alone or E2and testosterone in combination decreased the LDH release, increased the percentage of rod-shaped cells, reduced apoptotic cells (%), and combination treatment appeared to be more effective than either E2or testosterone replacement alone. ICI 118 551 abolished the effects of the three. Combination supplementation also enhanced the expression of β2-AR. We concluded that in Ovx rats, testosterone enhances E2's cardioprotection, while E2and testosterone in combination was more effective and the protective effects may be associated with β2-AR. The study highlights the potential therapeutic application for CVD in postmenopausal women.
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::25ca14e5bf0ad509fa0dd54e4f6d6514Test
https://doi.org/10.1530/joe-11-0181Test -
5
المؤلفون: Silvina Beatriz Meroni, Maria Fernanda Riera, Maria Noel Lujan Galardo, Eliana Herminia Pellizzari, Selva B. Cigorraga
المصدر: Reproduction. 133:763-773
مصطلحات موضوعية: Male, musculoskeletal diseases, Embryology, Morpholines, Blotting, Western, Interleukin-1beta, Mitogen-activated protein kinase kinase, Rats, Sprague-Dawley, Wortmannin, Phosphatidylinositol 3-Kinases, chemistry.chemical_compound, Endocrinology, Lactate dehydrogenase, Nitriles, Butadienes, medicine, Animals, Enzyme Inhibitors, skin and connective tissue diseases, Protein kinase B, Cells, Cultured, Phosphoinositide-3 Kinase Inhibitors, Flavonoids, Sirolimus, Sertoli Cells, L-Lactate Dehydrogenase, MAP kinase kinase kinase, Akt/PKB signaling pathway, Chemistry, Transferrin, Obstetrics and Gynecology, Cell Biology, musculoskeletal system, Sertoli cell, Stimulation, Chemical, Rats, Cell biology, Androstadienes, Enzyme Activation, medicine.anatomical_structure, Reproductive Medicine, Chromones, Lactates, Mitogen-Activated Protein Kinases, Proto-Oncogene Proteins c-akt, cGMP-dependent protein kinase, Immunosuppressive Agents, Signal Transduction
الوصف: Interleukin-1beta (IL1beta ) belongs to a set of intratesticular regulators that provide the fine-tuning of cellular processes implicated in the maintenance of spermatogenesis. The aim of the present study was to analyze the signaling pathways that may participate in IL1beta regulation of Sertoli cell function. Sertoli cell cultures from 20-day-old rat were used. Stimulation of the cultures with IL1beta showed increments in phosphorylated protein kinase B (PKB), P70S6K, and ERK1/2 levels. A phosphatidyl inositol 3-kinase (PI3K) inhibitor (wortmannin (W)), a mammalian target of rapamycin inhibitor (rapamycin (R)), and a MEK inhibitor (PD98059 (PD)) were utilized to evaluate the participation of PI3K/PKB, P70S6K, and ERK1/2 pathways in the regulation of lactate production by IL1beta . PD and W, but not R, decreased IL1beta-stimulated lactate production. The participation of these pathways in the regulation of glucose uptake and lactate dehydrogenase (LDH) A mRNA levels by IL1beta was also analyzed. It was observed that W decreased IL1beta-stimulated glucose uptake, whereas PD and R did not modify it. On the other hand, PD decreased the stimulation of LDH A mRNA levels by IL1beta , whereas W and R did not modify it. In summary, results presented herein demonstrate that IL1beta stimulates PI3K/PKB-, P70S6K-, and ERK1/2-dependent pathways in rat Sertoli cells. Moreover, these results show that while IL1beta utilizes the PI3K/PKB pathway to regulate glucose transport, it utilizes the ERK1/2 pathway to regulate LDH A mRNA levels. This study reveals that IL1beta utilizes different signal transduction pathways to modify the biochemical steps that are important to regulate lactate production in rat Sertoli cells.
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::507d806223ad8bcc1692e7f67eaa9315Test
https://doi.org/10.1530/rep.1.01091Test -
6
المصدر: Journal of Endocrinology. 184:191-197
مصطلحات موضوعية: Adult, Cytotoxicity, Immunologic, medicine.medical_specialty, Proline, T-Lymphocytes, Endocrinology, Diabetes and Metabolism, Estrogen receptor, Caspase 3, Biology, chemistry.chemical_compound, Interleukin 21, Endocrinology, Estrogen Receptor Modulators, Thiocarbamates, Internal medicine, Lactate dehydrogenase, medicine, Estrogen Receptor beta, Humans, Cytotoxic T cell, Cytotoxicity, Cells, Cultured, Estradiol, L-Lactate Dehydrogenase, Tumor Necrosis Factor-alpha, Estrogen Antagonists, Estrogen Receptor alpha, NF-kappa B, Immunohistochemistry, chemistry, Caspases, Interleukin 12, Female, Tumor necrosis factor alpha
الوصف: We determined the effect of 17β-estradiol on tumor necrosis factor α (TNF-α)-induced cytotoxicity in human peripheral T lymphocytes (T cells) using lactate dehydrogenase assay. Treatment with 17β-estradiol (1–100 nM) for 24 h showed dose-dependent reduction of TNF-α-induced cytotoxicity in T cells. To further evaluate the mechanism of 17β-estradiol on TNF-α-induced cytotoxicity in T cells, we identified estrogen receptor (ER) protein in T cells using immunocytochemistry and used the pure ER antagonist ICI 172,780. ERα immunoreactivity was clearly observed in T cells. ERβ immunoreactivity was also detected in some T cells. ICI 172,780 (10−7 M) alone did not affect cytotoxicity in T cells, however, ICI 172,780 (10−7 M) completely abolished 17β-estradiol cytoprotective effects in T cells. TNF-α tended to increase nuclear factor κB (NF-κB) protein levels in nuclear extracts but it did not reach statistical significance by Western blotting. In contrast, NF-κB protein levels in nuclear extracts followed by TNF-α with 17β-estradiol treatment were significantly increased compared with NF-κB protein levels in untreated group. NF-κB blocker pyrrolidinedithiocarbamate (PDTC) (10−4 M) alone did not affect cytotoxicity in T cells. In contrast, PDTC (10−4 M) completely abolished 17β-estradiol cytoprotective effects in T cells. Caspase -3/-7 activity was significantly increased followed by TNF-α, and 17β-estradiol treatment significantly reduced the increment. The present studies suggest the protective effect of 17β-estradiol on TNF-α-induced cytotoxicity through ERs in T cells and that NF-κB activation and caspase suppression may be involved in the mechanism.
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c4ff95f9bddf6d02479eaee9a4862d67Test
https://doi.org/10.1677/joe.1.05914Test -
7
المؤلفون: Gabriel Boaventura, Gustavo Casimiro-Lopes, Egberto Gaspar de Moura, C. C. Pazos-Moura, Patricia Cristina Lisboa, Elaine de Oliveira
المصدر: Journal of Endocrinology. 219:29-37
مصطلحات موضوعية: Male, medicine.medical_specialty, Offspring, Endocrinology, Diabetes and Metabolism, Mothers, Weaning, Motor Activity, chemistry.chemical_compound, Endocrinology, Physical Conditioning, Animal, Internal medicine, Lactation, medicine, Animals, Obesity, Rats, Wistar, Bromocriptine, Metabolic Syndrome, L-Lactate Dehydrogenase, medicine.diagnostic_test, Glycogen, business.industry, Muscles, Lipid Metabolism, medicine.disease, Prolactin, Rats, medicine.anatomical_structure, chemistry, Female, medicine.symptom, Metabolic syndrome, Lipid profile, business, Weight gain, medicine.drug
الوصف: The inhibition of maternal prolactin production in late lactation leads to metabolic syndrome and hypothyroidism in adult offspring. Physical training is a therapeutic strategy that could prevent or reverse this condition. We evaluated the effects of a short-duration low-intensity running wheel training program on the metabolic and hormonal alterations in rats. Lactating Wistar rats were treated with bromocriptine (Bro, 1 mg twice a day) or saline on days 19, 20, and 21 of lactation, and the training of offspring began at 35 days of age. Offspring were divided into sedentary and trained controls (C-Sed and C-Ex) and sedentary and trained Bro-treated rats (Bro-Sed and Bro-Ex). Chronic exercise delayed the onset of weight gain in Bro-Ex offspring, and the food intake did not change during the experimental period. At 180 days, visceral fat mass was higher (+46%) in the Bro-Sed offspring than in C-Sed and Bro-Ex rats. As expected, running capacity was higher in trained animals. Most parameters observed in the Bro-Sed offspring were consistent with hypothyroidism and metabolic syndrome and were reversed in the Bro-Ex group. Chronic exercise did not influence the muscle glycogen in the C-Ex group; however, liver glycogen was higher (+30%) in C-Ex group and was unchanged in both Bro offspring groups. Bro-Ex animals had higher plasma lactate dehydrogenase levels, indicating skeletal muscle damage and intolerance of the training program. Low-intensity chronic training is able to normalize many clinical aspects in Bro animals; however, these animals might have had a lower threshold for exercise adaptation than the control rats.
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::41b6a348637de46e6b828752d5787d53Test
https://doi.org/10.1530/joe-13-0102Test -
8
المؤلفون: Horng-Heng Juang, Shyi-Wu Wang, Phei-Lang Chang, Ke-Hung Tsui, Tsui-Hsia Feng, Li-Chuan Chung
المصدر: Journal of Molecular Endocrinology. 51:131-141
مصطلحات موضوعية: Male, Lactate dehydrogenase A, Biology, Endocrinology, Cell Line, Tumor, LNCaP, Gene expression, Humans, education, Molecular Biology, Aconitate Hydratase, Regulation of gene expression, education.field_of_study, Expression vector, Carcinoma, Prostatic Neoplasms, Hypoxia-Inducible Factor 1, alpha Subunit, Molecular biology, Cell Hypoxia, Mitochondria, Gene Expression Regulation, Neoplastic, Citric acid cycle, Fatty acid synthase, HIF1A, Gene Knockdown Techniques, biology.protein
الوصف: Hypoxia induces metabolic alteration in cancer cells by stabilizing hypoxia-inducible factor 1α (HIF-1α (HIF1A)), which regulates the bioenergetic genes of glycolysis and lipid metabolic pathways. However, the target genes of hypoxia-induced metabolic alterations in the prostate remain uncertain. Mitochondrial aconitase (mACON) (ACONM) is an enzyme that is central to carbohydrate and energy metabolism and is responsible for the interconversion of citrate to isocitrate as part of the citric acid cycle in the human prostate. We evaluated the effects of the molecular mechanisms of hypoxia onmACONgene expression in PC-3 and LNCaP human prostate carcinoma cells. Immunoblotting assays revealed that hypoxia modulated mACON and lactate dehydrogenase A (LDHA) protein expression, while these effects were attenuated whenHIF-1αwas knocked down. Hypoxia induced fatty acid synthase (FASN) in PC-3 cells while hypoxia blockedFASNgene expression in LNCaP cells after 24-h incubation. Results of real-time RT-qPCR, immunoblotting, and transient gene expression assays revealed that hypoxia treatment or co-transfection withHIF-1αexpression vector enhanced gene expression ofmACON, implying that hypoxia modulatedmACONat the transcriptional level. Hypoxia-inducedmACONpromoter activity is dependent on the DNA fragment located at −1013 to −842 upstream of the translation initiation site.l-mimosine, an iron chelator, stabilized HIF-1α but downregulatedmACONgene expression, suggesting that iron chelation blocked the hypoxia-inducedmACONgene expression. These results suggest that hypoxia dysregulates the expressions ofLDHA,FASN, andmACONgenes, and the hypoxia-inducedmACONgene expression is via the HIF-1α-dependent and iron-dependent pathways in prostate carcinoma cells.
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::48e48a4d165cfb0ea711f7bd5e12dceaTest
https://doi.org/10.1530/jme-13-0090Test -
9
المؤلفون: Pierre J. Courtoy, Michel Couvreur, M-F van den Hove, K Croizet, Maria Stoenoiu, Idesbald Colin, Olivier Devuyst
المصدر: Journal of Endocrinology. 173:177-185
مصطلحات موضوعية: medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Thyroid Gland, Nitric Oxide Synthase Type II, Biology, Nitric Oxide, Epithelium, Nitric oxide, Autoimmune thyroiditis, Interferon-gamma, chemistry.chemical_compound, Endocrinology, Lactate dehydrogenase, Internal medicine, medicine, Humans, Cytotoxicity, Cells, Cultured, Microscopy, Confocal, Cell Death, L-Lactate Dehydrogenase, Thyroid, Cell Polarity, Interleukin, medicine.disease, Nitric oxide synthase, NG-Nitroarginine Methyl Ester, Cytokine, medicine.anatomical_structure, chemistry, biology.protein, Nitric Oxide Synthase, Interleukin-1
الوصف: Nitric oxide (NO) is a well-known mediator of autoimmune processes. In the thyroid gland, it is produced in response to interleukin 1 (IL-1) and may mediate cytokine action at an early stage of autoimmune thyroiditis. In this study, we have investigated whether NO is involved in cytokine-induced cytotoxic effects and epithelial barrier alterations in thyrocytes. Human thyroid epithelial cells were cultured as tight polarised monolayers on a permeable support and exposed or not to IL-1alpha (100 U/ml), alone or in combination with interferon-gamma (IFN-gamma; 100 U/ml) added to the basal compartment. NO production was not detected in control thyrocytes, but was significantly induced by the combination of IL-1alpha with IFN-gamma, in a time-dependent fashion. Similarly, expression of the inducible isoform of nitric oxide synthase (NOSII), determined by immunoblot and immunofluorescence confocal microscopy, was not detected in control cells, but was markedly induced after 48-h exposure to both cytokines. This treatment significantly increased the release of cytosolic lactate dehydrogenase (LDH) in the apical and basolateral media and decreased transepithelial electrical resistance. Although IFN-gamma was not sufficient to induce NO production, it could by itself decrease transepithelial resistance and synergised the IL-1alpha effect on LDH release. The NOS inhibitor, L-nitro-arginine-methyl ester, suppressed the cytokine-induced NO production and decreased the LDH release, but failed to prevent the loss of transepithelial resistance. These results indicated that human thyrocytes express NOSII and produce NO in response to IL-1alpha+IFN-gamma and suggest that NO acts as a mediator of cytokine-induced cytotoxicity in the thyroid gland and may promote the exposure of autoantigens to the immune system. In contrast, NO does not appear to mediate the cytokine-induced disruption of the thyroid epithelial barrier.
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d0767d245d4cd65d62316367a8175c97Test
https://doi.org/10.1677/joe.0.1730177Test -
10
المؤلفون: D. K. O. Chan, Chris K. C. Wong
المصدر: Journal of Endocrinology. 168:185-192
مصطلحات موضوعية: Gills, Male, medicine.medical_specialty, Hydrocortisone, Endocrinology, Diabetes and Metabolism, ATPase, medicine.medical_treatment, Cell Separation, Epithelium, chemistry.chemical_compound, Endocrinology, Chlorides, Anguillidae, Internal medicine, Lactate dehydrogenase, medicine, Animals, Japanese eel, Cell Size, Analysis of Variance, L-Lactate Dehydrogenase, biology, Cell growth, Succinate dehydrogenase, Anguilla, Flow Cytometry, biology.organism_classification, Succinate Dehydrogenase, Steroid hormone, chemistry, Microscopy, Electron, Scanning, biology.protein, Female, Ca(2+) Mg(2+)-ATPase, Sodium-Potassium-Exchanging ATPase, Glucocorticoid, medicine.drug
الوصف: The purpose of the present study was to determine the effects of cortisol on the development of the freshwater chloride cell (CC), using flow cytometry. Scanning electron microscopy was used to determine the corresponding modifications in CC apical structure. Simultaneously, biochemical analyses were conducted to determine the activities of transport ATPases, mitochondrial enzymes (succinate dehydrogenase (SDH) and Mg(2+)-ATPase) and lactate dehydrogenase (Ldh). The effects of daily i.m. injection of 2 microg/g cortisol were compared with sham-injected freshwater-, control freshwater- and seawater-adapted fish. The hormone did not affect the activities of Ca(2+)-ATPases in CCs. However, it stimulated the proliferation and differentiation of the two freshwater CC subtypes (F1, 66+/-2.18% (s.e.m. ) and F2, 34+/-2.18%), in which the relative proportion of F1 CCs was transiently reduced in the first 5 days of treatment (F1, 53+/-1.83%; F2, 47+/-1.83%) but was then restored to a higher relative percentage on day 10 (F1, 70+/-1.42%; F2, 30+/-1.42%). Biochemically, it induced the activities of Na(+)/K(+)-ATPase, Mg(2+)-ATPase, SDH and Ldh, suggesting an increase in ion pumping and its associated metabolic activities. CCs from cortisoltreated fish demonstrated recessed apical morphology, accompanied by an increase in cell density (2012 to 2413/mm(2)). Nevertheless, the extent of cell proliferation and differentiation and the biochemical changes were significantly lower than those of seawater fish. Our results indicate that cortisol alone cannot stimulate a complete differentiation of freshwater CCs to seawater CCs. However, the respective roles of the two CC subtypes in freshwater and seawater environments are indicated.
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9d8c651db32772c49b564c3d4f85d887Test
https://doi.org/10.1677/joe.0.1680185Test
