scholarly journals Cadmium toxicity is caused by accumulation of p53 through the down-regulation of Ube2d family genes in vitro and in vivo

2011 ◽  
Vol 36 (2) ◽  
pp. 191-200 ◽  
Author(s):  
Maki Tokumoto ◽  
Yasuyuki Fujiwara ◽  
Akinori Shimada ◽  
Tatsuya Hasegawa ◽  
Yoshiyuki Seko ◽  
...  
Keyword(s):  
Cadmium Toxicity ◽  
Down Regulation

scholarly journals LINGO-1 shRNA protects the brain against ischemia/reperfusion injury by inhibiting the activation of NF-κB and JAK2/STAT3

Human Cell ◽  
2021 ◽  
Author(s):  
Jiaying Zhu ◽  
Zhu Zhu ◽  
Yipin Ren ◽  
Yukang Dong ◽  
Yaqi Li ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Nuclear Translocation ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Glucose Deprivation ◽  
Artery Occlusion ◽  
Mice Model ◽  
Down Regulation

AbstractLINGO-1 may be involved in the pathogenesis of cerebral ischemia. However, its biological function and underlying molecular mechanism in cerebral ischemia remain to be further defined. In our study, middle cerebral artery occlusion/reperfusion (MACO/R) mice model and HT22 cell oxygen–glucose deprivation/reperfusion (OGD/R) were established to simulate the pathological process of cerebral ischemia in vivo and in vitro and to detect the relevant mechanism. We found that LINGO-1 mRNA and protein were upregulated in mice and cell models. Down-regulation LINGO-1 improved the neurological symptoms and reduced pathological changes and the infarct size of the mice after MACO/R. In addition, LINGO-1 interference alleviated apoptosis and promoted cell proliferation in HT22 of OGD/R. Moreover, down-regulation of LINGO-1 proved to inhibit nuclear translocation of p-NF-κB and reduce the expression level of p-JAK2 and p-STAT3. In conclusion, our data suggest that shLINGO-1 attenuated ischemic injury by negatively regulating NF-KB and JAK2/STAT3 pathways, highlighting a novel therapeutic target for ischemic stroke.

GDNF and neurturin are target-derived factors essential for cranial parasympathetic neuron development

Development ◽  
2001 ◽  
Vol 128 (19) ◽  
pp. 3773-3782 ◽  
Author(s):  
Eri Hashino ◽  
Marlene Shero ◽  
Dirk Junghans ◽  
Hermann Rohrer ◽  
Jeffrey Milbrandt ◽  
...  
Keyword(s):  
Striate Muscle ◽  
Ciliary Ganglion ◽  
Neuron Development ◽  
Down Regulation ◽  
Eye Muscle ◽  
Ciliary Ganglion Neurons ◽  
Ganglion Neurons ◽  
Parasympathetic Neuron

During development, parasympathetic ciliary ganglion neurons arise from the neural crest and establish synaptic contacts on smooth and striate muscle in the eye. The factors that promote the ciliary ganglion pioneer axons to grow toward their targets have yet to be determined. Here, we show that glial cell line-derived neurotrophic factor (GDNF) and neurturin (NRTN) constitute target-derived factors for developing ciliary ganglion neurons. Both GDNF and NRTN are secreted from eye muscle located in the target and trajectory pathway of ciliary ganglion pioneer axons during the period of target innervation. After this period, however, the synthesis of GDNF declines markedly, while that of NRTN is maintained throughout the cell death period. Furthermore, both in vitro and in vivo function-blocking of GDNF at early embryonic ages almost entirely suppresses ciliary axon outgrowth. These results demonstrate that target-derived GDNF is necessary for ciliary ganglion neurons to innervate ciliary muscle in the eye. Since the down-regulation of GDNF in the eye is accompanied by down-regulation of GFRα1 and Ret, but not of GFRα2, in innervating ciliary ganglion neurons, the results also suggest that target-derived GDNF regulates the expression of its high-affinity coreceptors.

scholarly journals The Antidepressant Desipramine Is an Arrestin-biased Ligand at the α2A-Adrenergic Receptor Driving Receptor Down-regulation in Vitro and in Vivo

2011 ◽  
Vol 286 (41) ◽  
pp. 36063-36075 ◽  
Author(s):  
Christopher Cottingham ◽  
Yunjia Chen ◽  
Kai Jiao ◽  
Qin Wang
Keyword(s):  
Adrenergic Receptor ◽  
Antidepressant Drug ◽  
Antidepressant Drugs ◽  
Direct Interaction ◽  
Receptor Expression ◽  
Receptor Internalization ◽  
Down Regulation ◽  
Altered Expression

The neurobiological mechanisms of action underlying antidepressant drugs remain poorly understood. Desipramine (DMI) is an antidepressant classically characterized as an inhibitor of norepinephrine reuptake. Available evidence, however, suggests a mechanism more complex than simple reuptake inhibition. In the present study, we have characterized the direct interaction between DMI and the α2A-adrenergic receptor (α2AAR), a key regulator of noradrenergic neurotransmission with altered expression and function in depression. DMI alone was found to be sufficient to drive receptor internalization acutely and a robust down-regulation of α2AAR expression and signaling following prolonged stimulation in vitro. These effects are achieved through arrestin-biased regulation of the receptor, as DMI selectively induces recruitment of arrestin but not activation of heterotrimeric G proteins. Meanwhile, a physiologically relevant concentration of endogenous agonist (norepinephrine) was unable to sustain a down-regulation response. Prolonged in vivo administration of DMI resulted in significant down-regulation of synaptic α2AAR expression, a response that was lost in arrestin3-null animals. We contend that direct DMI-driven arrestin-mediated α2AAR down-regulation accounts for the therapeutically desirable but mechanistically unexplained adaptive alterations in receptor expression associated with this antidepressant. Our results provide novel insight into both the pharmacology of this antidepressant drug and the targeting of the α2AAR in depression.

Down-regulation of heparanase leads to the inhibition of invasion and proliferation of A549 cells in vitro and in vivo

2012 ◽  
Vol 45 (3) ◽  
pp. 188-193 ◽  
Author(s):  
Z. Chen ◽  
L. Zhu ◽  
X. Li ◽  
H. Tian ◽  
Y. Fang ◽  
...  
Keyword(s):  
A549 Cells ◽  
Down Regulation

scholarly journals Down regulation of BRCA2 causes radio-sensitization of human tumor cells in vitro and in vivo

2008 ◽  
Vol 99 (4) ◽  
pp. 810-815 ◽  
Author(s):  
Dong Yu ◽  
Emiko Sekine ◽  
Akira Fujimori ◽  
Takahiro Ochiya ◽  
Ryuichi Okayasu
Keyword(s):  
Tumor Cells ◽  
Human Tumor ◽  
Human Tumor Cells ◽  
Down Regulation

scholarly journals Requirement for Down-Regulation of the CCAAT-binding Activity of the NF-Y Transcription Factor during Skeletal Muscle Differentiation

2003 ◽  
Vol 14 (7) ◽  
pp. 2706-2715 ◽  
Author(s):  
Aymone Gurtner ◽  
Isabella Manni ◽  
Paola Fuschi ◽  
Roberto Mantovani ◽  
Fiorella Guadagni ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Cells ◽  
Cyclin B1 ◽  
Binding Activity ◽  
Down Regulation ◽  
Cardiac Muscle Cells ◽  
Differentiated Cells ◽  
Target Promoters

NF-Y is composed of three subunits, NF-YA, NF-YB, and NF-YC, all required for DNA binding. All subunits are expressed in proliferating skeletal muscle cells, whereas NF-YA alone is undetectable in terminally differentiated cells in vitro. By immunohistochemistry, we show that the NF-YA protein is not expressed in the nuclei of skeletal and cardiac muscle cells in vivo. By chromatin immunoprecipitation experiments, we demonstrate herein that NF-Y does not bind to the CCAAT boxes of target promoters in differentiated muscle cells. Consistent with this, the activity of these promoters is down-regulated in differentiated muscle cells. Finally, forced expression of the NF-YA protein in cells committed to differentiate leads to an impairment in the down-regulation of cyclin A, cyclin B1, and cdk1 expression and is accompanied by a delay in myogenin expression. Thus, our results indicate that the suppression of NF-Y function is of crucial importance for the inhibition of several cell cycle genes and the induction of the early muscle-specific program in postmitotic muscle cells.

scholarly journals LINC00641/miR-582-5p mediate oxaliplatin resistance by activating autophagy in gastric adenocarcinoma

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Yunfeng Hu ◽  
Yani Su ◽  
Xia Lei ◽  
Hong Zhao ◽  
Lelin Wang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Gastric Adenocarcinoma ◽  
Resistant Cell ◽  
Specific Mechanism ◽  
Gastric Cancer Cells ◽  
Down Regulation ◽  
Cancer Tissues ◽  
Cell Migration And Proliferation

Abstract The poor prognosis of gastric adenocarcinoma is partly due to chemotherapy failure, especially the oxaliplatin-based chemotherapy. However, the specific mechanism of oxaliplatin resistance is unclear. We aim to find the roles that LINC00641 and miR-582-5p play in regulating oxaliplatin resistance. Quantitative reverse transcriptase-PCR was used to evaluate the expression of LINC00641 and microRNA-582-5p (miR-582-5p) in gastric cancer both in vivo and in vitro. Transwell and CCK-8 assays were performed; and LC3 I/II and p62 were detected by western blot to evaluate the activation of autophagy. LINC00641 expression was associated with prognosis and oxaliplatin resistance in patients with gastric adenocarcinoma. The expression of LINC00641 was higher in gastric cancer tissues; whereas miR-582-5p was down-regulated in gastric cancer tissues. Moreover, LINC00641 was highly expressed in oxaliplatin-resistant cell lines and miR-582-5p was down-regulated. In addition, LINC00641 negatively regulated the expression of miR-582-5p. With regard to biological functions, down-regulation of LINC00641 suppressed cell migration and proliferation. Further experiments indicated that down-regulation of LINC00641 inhibited the autophagy process, making gastric cancer cells more sensitive to oxaliplatin. LINC00641 and miR-582-5p are biomarkers for predicting overall survival, as they were involved in regulating oxaliplatin resistance by altering autophagy in gastric adenocarcinoma.

scholarly journals The Effects of Cadmium Toxicity

2020 ◽  
Vol 17 (11) ◽  
pp. 3782 ◽  
Author(s):  
Giuseppe Genchi ◽  
Maria Stefania Sinicropi ◽  
Graziantonio Lauria ◽  
Alessia Carocci ◽  
Alessia Catalano
Keyword(s):  
Mammalian Cells ◽  
Dna Methyltransferase ◽  
Kidney Diseases ◽  
Cadmium Toxicity ◽  
Indian Mustard ◽  
Eucalyptus Camaldulensis ◽  
Micro Rna ◽  
Epigenetic Changes

Cadmium (Cd) is a toxic non-essential transition metal that poses a health risk for both humans and animals. It is naturally occurring in the environment as a pollutant that is derived from agricultural and industrial sources. Exposure to cadmium primarily occurs through the ingestion of contaminated food and water and, to a significant extent, through inhalation and cigarette smoking. Cadmium accumulates in plants and animals with a long half-life of about 25–30 years. Epidemiological data suggest that occupational and environmental cadmium exposure may be related to various types of cancer, including breast, lung, prostate, nasopharynx, pancreas, and kidney cancers. It has been also demonstrated that environmental cadmium may be a risk factor for osteoporosis. The liver and kidneys are extremely sensitive to cadmium’s toxic effects. This may be due to the ability of these tissues to synthesize metallothioneins (MT), which are Cd-inducible proteins that protect the cell by tightly binding the toxic cadmium ions. The oxidative stress induced by this xenobiotic may be one of the mechanisms responsible for several liver and kidney diseases. Mitochondria damage is highly plausible given that these organelles play a crucial role in the formation of ROS (reactive oxygen species) and are known to be among the key intracellular targets for cadmium. When mitochondria become dysfunctional after exposure to Cd, they produce less energy (ATP) and more ROS. Recent studies show that cadmium induces various epigenetic changes in mammalian cells, both in vivo and in vitro, causing pathogenic risks and the development of various types of cancers. The epigenetics present themselves as chemical modifications of DNA and histones that alter the chromatin without changing the sequence of the DNA nucleotide. DNA methyltransferase, histone acetyltransferase, histone deacetylase and histone methyltransferase, and micro RNA are involved in the epigenetic changes. Recently, investigations of the capability of sunflower (Helianthus annuus L.), Indian mustard (Brassica juncea), and river red gum (Eucalyptus camaldulensis) to remove cadmium from polluted soil and water have been carried out. Moreover, nanoparticles of TiO2 and Al2O3 have been used to efficiently remove cadmium from wastewater and soil. Finally, microbial fermentation has been studied as a promising method for removing cadmium from food. This review provides an update on the effects of Cd exposure on human health, focusing on the cellular and molecular alterations involved.

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