scholarly journals Estrogen receptors and estetrol-dependent neuroprotective actions: a pilot study

2017 ◽  
Vol 232 (1) ◽  
pp. 85-95 ◽  
Author(s):  
Ekaterine Tskitishvili ◽  
Christel Pequeux ◽  
Carine Munaut ◽  
Renaud Viellevoye ◽  
Michelle Nisolle ◽  
...  
Keyword(s):  
Estrogen Receptors ◽  
Cell Survival ◽  
Cell Cultures ◽  
Damage Model ◽  
Neuronal Cell ◽  
Concomitant Treatment ◽  
Ldh Activity

Estetrol (E4) has strong antioxidative, neurogenic and angiogenic effects in neural system resulting in the attenuation of neonatal hypoxic–ischemic encephalopathy. We aimed to define the role of estrogen receptors in E4-dependent actions in neuronal cell cultures and prove the promyelinating effect of E4. In vitro the antioxidative and cell survival/proliferating effects of E4 on H2O2-induced oxidative stress in primary hippocampal cell cultures were studied using different combinations of specific inhibitors for ERα (MPP dihydrochloride), ERβ (PHTTP), GPR30 (G15) and palmytoilation (2-BR). LDH activity and cell survival assays were performed. In vivo the promyelinating role of different concentrations of E4 (1 mg/kg/day, 5 mg/kg/day, 10 mg/kg/day, 50 mg/kg/day) was investigated using the hypoxic–ischemic brain damage model in the 7-day-old immature rats before/after the induction of hypoxic–ischemic insult. Myelin basic protein (MBP) immunostaining was performed on brain coronal sections. Our results show that LDH activity is significantly upregulated in cell cultures where the E4’s effect was completely blocked by concomitant treatment either with ERα and ERβ inhibitors (MPP and PHTPP, respectively), or ERα and ERβ inhibitors combined with 2-BR. Cell survival is significantly downregulated in cell cultures where the effect of E4 was blocked by ERβ inhibitor (PHTTP) alone. The blockage of GRP30 receptor did affect neither LDH activity nor cell survival. MBP immunostaining is significantly upregulated in E4-pretreated groups at a concentration of 5 mg/kg/day and 50 mg/kg/day E4, whereas the MBP-positive area OD ratio is significantly increased in all the E4-treated groups. E4’s antioxidative actions mostly depend on ERα and ERβ, whereas neurogenesis and possibly promyelinating activities might be realized through ERβ.

Role of the gut proteinases from mosquito larvae in the mechanism of action and the specificity of the Bacillus sphaericus toxin

1990 ◽  
Vol 36 (11) ◽  
pp. 804-807 ◽  
Author(s):  
Luc Nicolas ◽  
Anne Lecroisey ◽  
Jean-François Charles
Keyword(s):  
Cell Cultures ◽  
Spodoptera Littoralis ◽  
Mosquito Species ◽  
Bacillus Sphaericus ◽  
Cellular Level ◽  
Mosquito Cell ◽  
Mosquito Larvae

Gut proteinases from larvae of mosquito species both susceptible and not susceptible to Bacillus sphaericus converted the 43-kDa toxin to a 40-kDa polypeptide exhibiting enhanced cytotoxicity to mosquito cell cultures. The toxin was also activated by gut proteinases from the nonsusceptible Lepidoptera Spodoptera littoralis in vitro and in vivo. Therefore, the specificity of Bacillus sphaericus toxin does not seem to be determined by gut proteinase action. However, susceptibility of mosquito cell cultures did not reflect the specificity of the toxin, which must now be investigated at the cellular level in the larvae. Key words: mosquitoes, Bacillus sphaericus, bacterial toxins, proteinases, specificity.

scholarly journals CAPN1 (Calpain1)-Mediated Impairment of Autophagic Flux Contributes to Cerebral Ischemia-Induced Neuronal Damage

Stroke ◽  
2021 ◽  
Author(s):  
Yueyang Liu ◽  
Xiaohang Che ◽  
Haotian Zhang ◽  
Xiaoxiao Fu ◽  
Yang Yao ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Kinase Inhibitor ◽  
Neuronal Damage ◽  
Neuronal Cell ◽  
In Vivo Model ◽  
Autophagic Flux ◽  
Autophagosome Formation

Background and Purpose: CAPN1 (calpain1)—an intracellular Ca 2+ -regulated cysteine protease—can be activated under cerebral ischemia. However, the mechanisms by which CAPN1 activation promotes cerebral ischemic injury are not defined. Methods: In the present study, we used adeno-associated virus-mediated genetic knockdown and pharmacological blockade (MDL-28170) of CAPN1 to investigate the role of CAPN1 in the regulation of the autophagy-lysosomal pathway and neuronal damage in 2 models, rat permanent middle cerebral occlusion in vivo model and oxygen-glucose–deprived primary neuron in vitro model. Results: CAPN1 was activated in the cortex of permanent middle cerebral occlusion–operated rats and oxygen-glucose deprivation–exposed neurons. Genetic and pharmacological inhibition of CAPN1 significantly attenuated ischemia-induced lysosomal membrane permeabilization and subsequent accumulation of autophagic substrates in vivo and in vitro. Moreover, inhibition of CAPN1 increased autophagosome formation by decreasing the cleavage of the autophagy regulators BECN1 (Beclin1) and ATG (autophagy-related gene) 5. Importantly, the neuron-protective effect of MDL-28170 on ischemic insult was reversed by cotreatment with either class III-PI3K (phosphatidylinositol 3-kinase) inhibitor 3-methyladenine or lysosomal inhibitor chloroquine (chloroquine), suggesting that CAPN1 activation-mediated impairment of autophagic flux is crucial for cerebral ischemia-induced neuronal damage. Conclusions: The present study demonstrates for the first time that ischemia-induced CAPN1 activation impairs lysosomal function and suppresses autophagosome formation, which contribute to the accumulation of substrates and aggravate the ischemia-induced neuronal cell damage. Our work highlights the vital role of CAPN1 in the regulation of cerebral ischemia–mediated autophagy-lysosomal pathway defects and neuronal damage.

scholarly journals Application of three-dimensional neuronal cell cultures in the studies of mechanisms of neurodegenerative diseases

2017 ◽  
Vol 71 (1) ◽  
pp. 0-0 ◽  
Author(s):  
Anna Słońska ◽  
Joanna Cymerys
Keyword(s):  
Neurodegenerative Diseases ◽  
Cell Cultures ◽  
Three Dimensional ◽  
Neuronal Cell ◽  
3D Models ◽  
In Vitro Models ◽  
Gene And Protein Expression ◽  
Or Gene

In vitro models utilizing cells in planar two-dimensional (2D) cultures do not reflect the in vivo environment and are increasingly replaced by three-dimensional (3D) cultures. Fundamental differences between 2D and 3D cell cultures systems include cell attach, spread and grow, their morphology, proliferation, differentiation or gene and protein expression. For that reason 3D models have been proven to be invaluable tools of study for the various fields of science, such as drug discovery, cancer research, differentiation studies or neuroscience. In the present review, we discuss 3D neural in vitro models that might provide important insides about the mechanisms of pathogenesis of neurodegenerative diseases.

scholarly journals Role of zinc along with ascorbic acid and folic acid during long-term in vitro albumin glycation

2009 ◽  
Vol 103 (3) ◽  
pp. 370-377 ◽  
Author(s):  
Rashmi Santosh Tupe ◽  
Vaishali Vilas Agte
Keyword(s):  
Ascorbic Acid ◽  
Folic Acid ◽  
Cell Survival ◽  
Advanced Glycation Endproducts ◽  
Glycation Endproducts ◽  
Protein Thiols ◽  
Carbonyl Formation

The present study aimed to investigate the role of Zn alone and in the presence of ascorbic acid (AA) and folic acid (FA) in albumin glycation. Glycation was performed by incubations of bovine serum albumin with glucose at 37°C along with Zn, AA or FA separately and Zn+AA or Zn+FA for 150 d. Glycation-mediated modifications were monitored as fluorescence of advanced glycation endproducts, carbonyl formation, β aggregation (thioflavin T and Congo red dyes), albumin-bound Zn, thiol groups and glycated aggregate's toxicity in HepG2 cells. Zn inhibited glycation and β aggregation, probably due to observed higher protein-bound Zn. It also protected protein thiols and increased cell survival. AA and FA enhanced glycation, which was lowered in Zn-co-incubated samples. FA increased albumin-bound Zn and showed maximum cell survival. Although these results warrant further in vivo investigation, the present data help in the understanding of the interplay of Zn with micronutrients in albumin glycation.

Effect of triiodothyronine administration on estrogen receptor contents in peripuberal Sertoli cells

1996 ◽  
Vol 134 (5) ◽  
pp. 633-638 ◽  
Author(s):  
ML Panno ◽  
D Sisci ◽  
M Salerno ◽  
M Lanzino ◽  
L Mauro ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Thyroid Hormone ◽  
Estrogen Receptors ◽  
Sertoli Cells ◽  
Androgen Metabolism ◽  
Testicular Steroids ◽  
In Vivo Administration

Panno ML, Sisci D, Salerno M, Lanzino M, Mauro L, Morrone EG, Pezzi V, Palmero S. Fugassa E, Andò S. Effect of triiodothyronine administration on estrogen receptor contents in peripuberal Sertoli cells. Eur J Endocrinol 1996:134:633–8. ISSN 0804–4643 The effects of thyroid hormone on androgen metabolism in peripuberal Sertoli cells through the inhibition of estradiol production have been reported previously. It was our intention to investigate further the possible role of thyroid hormone on the interaction between testicular steroids and Sertoli cells by analyzing the effects of triiodothyronine (T3) on estrogen receptor content in 2-, 3- and 4week-old euthyroid rats. Triiodothyronine treatment (3 μg/100 body wt per day) given during the last week prior to sacrifice resulted in reduced testicular growth in 2-week-old animals. Sertoli cells from all groups were cultured initially under basal conditions for the first 24 h and subsequently in the presence of testosterone and/or T3 for the additional 24 h. The in vitro addition of T3 induced a decrease of estrogen receptors (ERs) in 2- and 3-week-old animals that appeared more pronounced especially in the presence of T3 and testosterone. When T3 was tested in vivo we noticed that the decrease of ER content was even greater in all three groups under the in vitro influence of both T3 and testosterone. In 3-week-old animals a simultaneous assay of ERs in both nuclear and cytoplasmic compartments was performed. The ER concentrations in the nucleus were closely related to those of the cytoplasm. The in vivo administration of T3 was responsible for a greater decrease of ERs in the nucleus than in the cytosol. On the basis of these results, and in agreement with our previous data, we speculate that the effect of T3 in the maturational events of Sertoli cells could involve both estradiol production and ER content. Sebastiano Andò Cattedra di Fisiopatologia Endocrina, Dipartimento di Biologia Cellulare, Università della Calabria, 87030 Arcavacata di Rende, Cosenza, Italy

scholarly journals The Pim kinases control rapamycin-resistant T cell survival and activation

2005 ◽  
Vol 201 (2) ◽  
pp. 259-266 ◽  
Author(s):  
Casey J. Fox ◽  
Peter S. Hammerman ◽  
Craig B. Thompson
Keyword(s):  
Immune Response ◽  
T Cells ◽  
T Cell ◽  
Cell Survival ◽  
Growth And Survival ◽  
Pim Kinases ◽  
T Cell Survival

Although Pim-1 or Pim-2 can contribute to lymphoid transformation when overexpressed, the physiologic role of these kinases in the immune response is uncertain. We now report that T cells from Pim-1−/−Pim-2−/− animals display an unexpected sensitivity to the immunosuppressant rapamycin. Cytokine-induced Pim-1 and Pim-2 promote the rapamycin-resistant survival of lymphocytes. The endogenous function of the Pim kinases was not restricted to the regulation of cell survival. Like the rapamycin target TOR, the Pim kinases also contribute to the regulation of lymphocyte growth and proliferation. Although rapamycin has a minimal effect on wild-type T cell expansion in vitro and in vivo, it completely suppresses the response of Pim-1−/−Pim-2−/− cells. Thus, endogenous levels of the Pim kinases are required for T cells to mount an immune response in the presence of rapamycin. The existence of a rapamycin-insensitive pathway that regulates T cell growth and survival has important implications for understanding how rapamycin functions as an immunomodulatory drug and for the development of complementary immunotherapeutics.

Role of osteoprotegerin (OPG) in cancer

2006 ◽  
Vol 110 (3) ◽  
pp. 279-291 ◽  
Author(s):  
Ingunn Holen ◽  
Claire M. Shipman
Keyword(s):  
Cell Survival ◽  
Tumour Cell ◽  
Bone Disease ◽  
In Vitro Models ◽  
Tumour Cells ◽  
Tumour Necrosis Factor Receptor ◽  
Area Of Interest

OPG (osteoprotegerin), a secreted member of the TNF (tumour necrosis factor) receptor superfamily, has a variety of biological functions which include the regulation of bone turnover. OPG is a potent inhibitor of osteoclastic bone resorption and has been investigated as a potential therapeutic for the treatment of both osteoporosis and tumour-induced bone disease. Indeed, in murine models of cancer-induced bone disease, inhibition of osteoclastic activity by OPG was also associated with a reduction in tumour burden. The discovery that OPG can bind to and inhibit the activity of TRAIL (TNF-related apoptosis-inducing ligand) triggered extensive research into the potential role of OPG in the regulation of tumour cell survival. A number of reports from studies using in vitro models have shown that OPG protects tumour cells from the effects of TRAIL, thereby possibly providing tumour cells that produce OPG with a survival advantage. However, the ability of OPG to act as a tumour cell survival factor remains to be verified using appropriate in vivo systems. A third area of interest has been the use of OPG as a prognostic marker in various cancer types, including myeloma, breast and prostate cancer. This review provides an overview of the role of OPG in cancer, both in cancer-induced bone disease and in tumour growth and survival.

scholarly journals Ginsenoside F1 Protects the Brain against Amyloid Beta-Induced Toxicity by Regulating IDE and NEP

Life ◽  
2022 ◽  
Vol 12 (1) ◽  
pp. 58
Author(s):  
Yee-Jin Yun ◽  
Bong-Hwan Park ◽  
Jingang Hou ◽  
Jung-Pyo Oh ◽  
Jin-Hee Han ◽  
...  
Keyword(s):  
Amyloid Beta ◽  
Neuronal Cell ◽  
Insulin Degrading Enzyme ◽  
Human Neuroblastoma ◽  
Aβ Aggregation ◽  
Neuronal Cell Lines ◽  
The Brain

Ginsenoside F1, the metabolite of Rg1, is one of the most important constituents of Panax ginseng. Although the effects of ginsenosides on amyloid beta (Aβ) aggregation in the brain are known, the role of ginsenoside F1 remains unclear. Here, we investigated the protective effect of ginsenoside F1 against Aβ aggregation in vivo and in vitro. Treatment with 2.5 μM ginsenoside F1 reduced Aβ-induced cytotoxicity by decreasing Aβ aggregation in mouse neuroblastoma neuro-2a (N2a) and human neuroblastoma SH-SY5Y neuronal cell lines. Western blotting, real-time PCR, and siRNA analysis revealed an increased level of insulin-degrading enzyme (IDE) and neprilysin (NEP). Furthermore, liquid chromatography with tandem mass spectrometry (LC-MS/MS) analysis confirmed that ginsenoside F1 could pass the blood–brain barrier within 2 h after administration. Immunostaining results indicate that ginsenoside F1 reduces Aβ plaques in the hippocampus of APPswe/PSEN1dE9 (APP/PS1) double-transgenic Alzheimer’s disease (AD) mice. Consistently, increased levels of IDE and NEP protein and mRNA were observed after the 8-week administration of 10 mg/kg/d ginsenoside F1. These data indicate that ginsenoside F1 is a promising therapeutic candidate for AD.

scholarly journals Estrogen Receptors as Molecular Targets of Endocrine Therapy for Glioblastoma

2021 ◽  
Vol 22 (22) ◽  
pp. 12404
Author(s):  
Andrea Magali González-Mora ◽  
Patricia Garcia-Lopez
Keyword(s):  
Estrogen Receptors ◽  
Endocrine Therapy ◽  
In Vivo Studies ◽  
The Family ◽  
Plasmatic Membrane ◽  
The Central Nervous System ◽  
Degree Of Malignancy

Hormonal factors may participate in the development and progression of glioblastoma, the most aggressive primary tumor of the central nervous system. Many studies have been conducted on the possible involvement of estrogen receptors (ERs) in gliomas. Since there is a tendency for a reduced expression of ERs as the degree of malignancy of such tumors increases, it is important to understand the role of these receptors in the progression and treatment of this disease. ERs belong to the family of nuclear receptors, although they can also be in the plasmatic membrane, cytoplasm and mitochondria. They are classified as estrogen receptors alpha and beta (ER⍺ and ERβ), each with different isoforms that have a distinct function in the organism. ERs regulate multiple physiological and pathological processes through the activation of genomic and nongenomic pathways in the cell. Nevertheless, the role of each isoform in the development and progression of glioblastoma is not completely clear. Diverse in vitro and in vivo studies have shown encouraging results for endocrine therapy as a treatment for gliomas. At the same time, many questions have arisen concerning the nature of ERs as well as the mechanism of action of the proposed drugs. Hence, the aim of the current review is to describe the drugs that could possibly be utilized in endocrine therapy for the treatment of high-grade gliomas, analyze their interaction with ERs, and explore the involvement of these drugs and receptors in resistance to standard chemotherapy.

scholarly journals Marine Compound Xyloketal B as a Potential Drug Development Target for Neuroprotection

Marine Drugs ◽  
2018 ◽  
Vol 16 (12) ◽  
pp. 516 ◽  
Author(s):  
Haifan Gong ◽  
Zhengwei Luo ◽  
Wenliang Chen ◽  
Zhong-Ping Feng ◽  
Guan-Lei Wang ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Stroke Treatment ◽  
Stroke Models ◽  
Marine Compound ◽  
Causes Of Mortality

Xyloketal B is a natural compound isolated from the mangrove fungus, Xylaria sp. in the South China Sea. In the past decade, studies have shown that xyloketal B exhibits anti-oxidative, anti-inflammatory, and anti-apoptotic abilities and may serve as a treatment for ischemic stroke. Xyloketal B has been shown to interact with both neurons and residential microglial cells and regulate a number of proteins involved in the apoptotic events during ischemia. Such mechanisms include inhibition of specific NADPH oxidase subunits, upregulation of HO-1, increase of Bcl-1/Bax ratio, and downregulation of TLR4 receptor. Both in vitro and in vivo stroke models have validated its potential in preventing ischemia-induced neuronal cell death. This review summarizes our current understanding of the effects of xyloketal B in ischemic conditions. As stroke ranks second in the causes of mortality worldwide and still lacks effective treatment, it is necessary to seek novel therapeutic options. Understanding the role of xyloketal B in ischemic stroke could reveal a new aspect of stroke treatment.

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