scholarly journals Taurine Promotes Axonal Sprouting Through Mitochondrial Improvement in Stroke

2021 ◽  
Author(s):  
Weiliang He ◽  
Xiaochao Tian ◽  
Kaihua Zhang ◽  
Hebo Wang
Keyword(s):  
Transcription Factor ◽  
Ischemic Stroke ◽  
Motor Function ◽  
Brain Plasticity ◽  
Experimental Stroke ◽  
Peroxisome Proliferator ◽  
Axonal Sprouting ◽  
Peroxisome Proliferator Activated Receptor ◽  
Cortical Ischemia ◽  
Cerebral Ischemic

Abstract BackgroundBrain plasticity including axonal sprouting has been recognized in restoring motor function in ischemic stroke. Mitochondrion plays a crucial role in determining axonal sprouting in ischemic injury. Taurine (TAU) could protect brain against experimental stroke as one of the richest amino acids. However, the role of TAU on axonal sprouting and the specific potential mechanism on mitochondria of stroke were unclear. MethodsFocal cerebral cortical ischemia in C57BL/6 mice was preceded. Motor function was assayed by the Rota-Rod test on D7, D14, and D28 after stroke. Axonal sprouting was detected using immunocytochemistry with biotinylated dextran amine (BDA). The expressions of mitochondrial DNA (mtDNA), Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PCG-1a) and Transcription factor A of mitochondria (TFAM) were measured by RT-qPCR. ResultsTAU treatment significantly recovered the motor function of focal cerebral cortical ischemic mice. And TAU promoted axonal sprouting. It was also observed that TAU enhanced mtDNA content, increased the levels of Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PCG-1a) and Transcription factor A of mitochondria (TFAM). ConclusionsCollectively, the data illustrated that TAU exerted a promoting influence on axonal sprouting, through mitochondrial improvement in cerebral ischemic stroke.

scholarly journals RT-PCR analysis of corticotroph-associated genes expression in carcinoid tumours in the ectopic-ACTH syndrome

2006 ◽  
Vol 154 (1) ◽  
pp. 159-166 ◽  
Author(s):  
M Messager ◽  
C Carrière ◽  
X Bertagna ◽  
Y de Keyzer
Keyword(s):  
Transcription Factor ◽  
Molecular Mechanisms ◽  
Ectopic Acth Syndrome ◽  
Pcr Analysis ◽  
Peroxisome Proliferator ◽  
Rt Pcr ◽  
Ectopic Acth ◽  
Peroxisome Proliferator Activated Receptor ◽  
Carcinoid Tumours ◽  
Transcription Factor Genes

Objective: ACTH is frequently produced in non-pituitary tumours, leading to the ectopic-ACTH syndrome, but the molecular mechanisms of its expression remain obscure. This study was aimed at understanding the transcription mechanisms of the ACTH-precursor gene in carcinoid tumours of the lung or thymus. Design: Transcripts coding for a series of corticotroph-associated transcription factor genes were detected, together with markers of the corticotroph phenotype. We studied a series of 41 carcinoid tumours including 15 with proven ectopic-ACTH syndrome. Methods: Specific RT-PCR reactions were designed for each gene including alternatively spliced isoforms. Results: The markers of the corticotroph phenotype were detected in all ACTH-positive tumours. Expression of the Tpit and Pitx1 genes were not restricted to ACTH-positive tumours but were also detected in many ACTH-negative carcinoids. Only a subset of ACTH-negative tumours expressed NAK-1/Nur77, and NeuroD1 expression was detected in <50% of the tumours regardless of their secretory status. The glucocorticoid receptor alpha was detected in every tumour in contrast to its beta isoform detectable in a few tumours only. Chicken ovalbumin upstream promoter-transcription factor 1 (COUP-TF1) and peroxisome proliferator-activated receptor (PPAR) γ2 were expressed in 50% of the tumours of each group whereas PPARγ1 was expressed in almost every tumour. Conclusions: ACTH-positive carcinoids do not share a characteristic expression pattern of the corticotroph-associated transcription factor genes, suggesting that the transcriptional mechanisms of the ACTH-precursor gene differ from those in normal pituitary corticotrophs. Expression of Tpit and Pitx1 genes in most carcinoids suggests that some aspects of the pituitary corticotroph phenotype may belong to general carcinoid differentiation.

Abstract TP96: Functional Recovery and White Matter Repair After Exosomes Administration in Different Experimental Animal Models of Stroke

Stroke ◽  
2016 ◽  
Vol 47 (suppl_1) ◽  
Author(s):  
Laura Otero Ortega ◽  
María Gutiérrez Fernández ◽  
Berta Rodríguez Frutos ◽  
Jaime Ramos Cejudo ◽  
Irene Lorenzo Llorente ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
White Matter ◽  
Functional Recovery ◽  
Brain Plasticity ◽  
Trophic Factors ◽  
Lesion Volume ◽  
Axonal Sprouting ◽  
Control Groups ◽  
Myelin Formation ◽  
White Matter Repair

Introduction: Extracellular vesicles such as exosomes has opened a new field of research. Exosomes are able to transfer DNAs, mRNAs, microRNAs, non-coding RNAs, proteins, trophic factors and lipids associated with brain plasticity enhancement after stroke. Aim: To investigate white matter repair after exosomes administration in two experimental models of subcortical stroke: ischemic and hemorrhage. Material/Methods: Subcortical ischemic stroke was induced by Endothelin-1 and Collagenase IV was used to induce subcortical hemorrhagic stroke into striatum. Intravenous exosomes or saline only were administrated at 24h after cerebral infarct as treatment. Exosomes were isolated from culture of adipose mesenchymal stem cell and they were characterized by Nanoshight, Electronic microscope, Western blot and Immunofluorescence. Proteins contained into exosomes were analyzed by Orbitrab. We analyzed functional recovery by Rotarod, beam walking and Rogers tests. Lesion volume and tract connectivity were studied by magnetic resonance image. Anterograde and retrograde tracers were used to analyze axonal sprouting. Myelin formation was analyzed by cryomielin. Results: Proteomics analysis of exosomes identified more than 1400 proteins, many of them involved in intercellular communication. DiI labeled-Exosomes were detected in brain and peripheral organs (liver, lung and spleen). After 28 days, treated groups showed smaller functional deficit compared to control groups in both hemorrhagic and ischemic models. Moreover, treated group showed an increase in tract connectivity at 7 and 28 days compared to control groups. Also, animals which received exosomes showed an increase axonal sprouting and myelin formation at 28 days after stroke in both hemorrhagic and ischemic stroke. The treated groups also showed higher levels of white matter-associated markers in the injured area than the control groups. Conclusion: White matter integrity in different subcortical strokes is in part restored by exosomes treatment, probably mediated by repair molecular factors implicated in axonal sprouting, remyelination and oligodendrogenesis. These findings are associated with improved functional recovery in both kinds of strokes.

scholarly journals Screening of Prognostic Factors in Early-Onset Breast Cancer

2020 ◽  
Vol 19 ◽  
pp. 153303381989367 ◽  
Author(s):  
Zhun Yu ◽  
Qi He ◽  
Guoping Xu
Keyword(s):  
Breast Cancer ◽  
Transcription Factor ◽  
Differentially Expressed Genes ◽  
Early Onset ◽  
Differentially Expressed ◽  
Peroxisome Proliferator ◽  
Early Onset Breast Cancer ◽  
Microrna Target ◽  
Peroxisome Proliferator Activated Receptor ◽  
Protein Protein Interaction

Background: Gene expression profiles from early-onset breast cancer and normal tissues were analyzed to explore the genes and prognostic factors associated with breast cancer. Methods: GSE109169 and GSE89116 were obtained from the database of Gene Expression Omnibus. We firstly screened the differentially expressed genes between tumor samples and normal samples from patients with early-onset breast cancer. Based on database for annotation, visualization and intergrated discovery (DAVID) tool, functional analysis was calculated. Transcription factor-target regulation and microRNA-target gene network were constructed using the tool of transcriptional regulatory relatitionships unraveled by sentence-based text mining (TRRUST) and miRWalk2.0, respectively. The prognosis-related survival information was compiled based on The Cancer Genome Atlas breast cancer clinical data. Results: A total of 708 differentially expressed genes from GSE109169 data sets and 358 differentially expressed genes from GSE89116 data sets were obtained, of which 122 common differentially expressed genes including 102 uniformly downregulated genes and 20 uniformly upregulated genes were screened. Protein–protein interaction network with a total of 83 nodes and 157 relationship pairs was obtained, and genes in protein–protein interaction, such as peroxisome proliferator-activated receptor γ, FGF2, adiponectin, and PCK1, were recognized as key nodes in protein–protein interaction. In total, 66 transcription factor–target relationship pairs were obtained, and peroxisome proliferator-activated receptor γ was the only one downregulated transcription factor. MicroRNA-target gene network contained 368 microRNA-target relationship pairs. Moreover, 16 differentially expressed genes, including 2 upregulations and 14 downregulations, were related to a significant correlation with the prognosis, including SQLE and peroxisome proliferator-activated receptor γ. Conclusions: SQLE and peroxisome proliferator-activated receptor γ might be important prognostic factors in breast cancers, and adiponectin might be important in breast cancer pathogenesis regulated by peroxisome proliferator-activated receptor γ.

scholarly journals CREB Activation Induces Adipogenesis in 3T3-L1 Cells

2000 ◽  
Vol 20 (3) ◽  
pp. 1008-1020 ◽  
Author(s):  
Jane E. B. Reusch ◽  
Lilliester A. Colton ◽  
Dwight J. Klemm
Keyword(s):  
Transcription Factor ◽  
Dominant Negative ◽  
Marker Genes ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Fatty Acid Binding ◽  
Fat Composition ◽  
Specific Factors ◽  
Necessary And Sufficient ◽  
Physiological And Biochemical

ABSTRACT Obesity is the result of numerous, interacting behavioral, physiological, and biochemical factors. One increasingly important factor is the generation of additional fat cells, or adipocytes, in response to excess feeding and/or large increases in body fat composition. The generation of new adipocytes is controlled by several “adipocyte-specific” transcription factors that regulate preadipocyte proliferation and adipogenesis. Generally these adipocyte-specific factors are expressed only following the induction of adipogenesis. The transcription factor(s) that are involved in initiating adipocyte differentiation have not been identified. Here we demonstrate that the transcription factor, CREB, is constitutively expressed in preadipocytes and throughout the differentiation process and that CREB is stimulated by conventional differentiation-inducing agents such as insulin, dexamethasone, and dibutyryl cAMP. Stably transfected 3T3-L1 preadipocytes were generated in which we could induce the expression of either a constitutively active CREB (VP16-CREB) or a dominant-negative CREB (KCREB). Inducible expression of VP16-CREB alone was sufficient to initiate adipogenesis as determined by triacylglycerol storage, cell morphology, and the expression of two adipocyte marker genes, peroxisome proliferator activated receptor gamma 2, and fatty acid binding protein. Alternatively, KCREB alone blocked adipogenesis in cells treated with conventional differentiation-inducing agents. These data indicate that activation of CREB was necessary and sufficient to induce adipogenesis. Finally, CREB was shown to bind to putative CRE sequences in the promoters of several adipocyte-specific genes. These data firmly establish CREB as a primary regulator of adipogenesis and suggest that CREB may play similar roles in other cells and tissues.

Sovateltide (IRL-1620) affects neuronal progenitors and prevents cerebral tissue damage after ischemic stroke

2020 ◽  
Vol 98 (9) ◽  
pp. 659-666 ◽  
Author(s):  
Amaresh K. Ranjan ◽  
Seema Briyal ◽  
Divya Khandekar ◽  
Anil Gulati
Keyword(s):  
Ischemic Stroke ◽  
Motor Function ◽  
Infarct Volume ◽  
Neural Regeneration ◽  
Stem Cell Markers ◽  
Cerebral Tissue ◽  
Differentiation Markers ◽  
Neuronal Progenitors ◽  
Endothelin B ◽  
Cerebral Ischemic

Stimulation of endothelin B receptors by its agonist IRL-1620 (INN, sovateltide) provides neuroprotection and neurological and motor function improvement following cerebral ischemia. We investigated the effect of sovateltide on stem and progenitor cells mediated neural regeneration and its effect on the cerebral tissue repair and restoration of neurological and motor function. Sovateltide (5 μg/kg) was injected intravenously in permanent middle cerebral artery occluded (MCAO) rats at 4, 6, and 8 h at days 0, 3, and 6. Neurological and motor function tests were carried out pre-MCAO and at day 7 post-MCAO. At day 7, significantly reduced expression of neuronal differentiation markers HuC/HuD and NeuroD1 was seen in MCAO + vehicle than sham rats. Sovateltide treatment upregulated HuC/HuD and NeuroD1 compared to MCAO + vehicle and their expression was similar to sham. Expression of stem cell markers Oct 4 and Sox 2 was similar in rats of all of the groups. Significantly reduced infarct volume and DNA damage with recovery of neurological and motor function was observed in sovateltide-treated MCAO rats. These results indicate that sovateltide initiates a regenerative response by promoting differentiation of neuronal progenitors and maintaining stem cells in an equilibrium following cerebral ischemic stroke.

scholarly journals Peroxisome proliferator-activated receptor γ and retinoid X receptor transcription factors are released from activated human platelets and shed in microparticles

2008 ◽  
Vol 99 (01) ◽  
pp. 86-95 ◽  
Author(s):  
Sherry L Spinelli ◽  
Stephen J Pollock ◽  
Thomas I Murant ◽  
Jamie J O’Brien ◽  
Neil Blumberg ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Platelet Activation ◽  
Human Platelets ◽  
Retinoid X Receptor ◽  
Complex Spectrum ◽  
Peroxisome Proliferator ◽  
Monocytic Cell ◽  
Peroxisome Proliferator Activated Receptor ◽  
Pparγ Agonist ◽  
New Findings

SummaryPeroxisome proliferator-activated receptor γ (PPARγ) and its ligands are important regulators of lipid metabolism, inflammation, and diabetes. We previously demonstrated that anucleate human platelets express the transcription factor PPARγ and that PPARγ ligands blunt platelet activation. To further understand the nature of PPARγ in platelets, we determined the platelet PPARγ isoform(s) and investigated the fate of PPARγ following platelet activation. Our studies demonstrated that human platelets contain only the PPARγ1 isoform and after activation with thrombin, TRAP, ADP or collagen PPARγ is released from internal stores. PPARγ release was blocked by a cytoskeleton inhibitor, Latrunculin A. Platelet-released PPARγ was complexed with the retinoid X receptor (RXR) and retained its ability to bind DNA. Interestingly, the released PPARγ and RXR were microparticle associated and the released PPARγ/RXR complex retained DNA-binding ability. Additionally, a monocytic cell line, THP-1, is capable of internalizing PMPs. Further investigation following treatment of these cells with the PPARγ agonist, rosiglitazone and PMPs revealed a possible transcellular mechanism to attenuate THP-1 activation. These new findings are the first to demonstrate transcription factor release from platelets, revealing the complex spectrum of proteins expressed and expelled from platelets, and suggests that platelet PPARγ has an undiscovered role in human biology.

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