scholarly journals G-quadruplexes Stabilization Upregulates CCN1 and Accelerates Aging in Cultured Cerebral Endothelial Cells

2022 ◽  
Vol 2 ◽  
Author(s):  
Brian Noh ◽  
Maria P. Blasco-Conesa ◽  
Yun-Ju Lai ◽  
Bhanu Priya Ganesh ◽  
Akihiko Urayama ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cognitive Deficits ◽  
Matricellular Protein ◽  
Gene Target ◽  
Aged Mice ◽  
Cerebral Endothelial Cells ◽  
Dna And Rna ◽  
Rna Stabilization ◽  
Cerebral Microvessel

Senescence in the cerebral endothelium has been proposed as a mechanism that can drive dysfunction of the cerebral vasculature, which precedes vascular dementia. Cysteine-rich angiogenic inducer 61 (Cyr61/CCN1) is a matricellular protein secreted by cerebral endothelial cells (CEC). CCN1 induces senescence in fibroblasts. However, whether CCN1 contributes to senescence in CEC and how this is regulated requires further study. Aging has been associated with the formation of four-stranded Guanine-quadruplexes (G4s) in G-rich motifs of DNA and RNA. Stabilization of the G4 structures regulates transcription and translation either by upregulation or downregulation depending on the gene target. Previously, we showed that aged mice treated with a G4-stabilizing compound had enhanced senescence-associated (SA) phenotypes in their brains, and these mice exhibited enhanced cognitive deficits. A sequence in the 3′-UTR of the human CCN1 mRNA has the ability to fold into G4s in vitro. We hypothesize that G4 stabilization regulates CCN1 in cultured primary CEC and induces endothelial senescence. We used cerebral microvessel fractions and cultured primary CEC from young (4-months old, m/o) and aged (18-m/o) mice to determine CCN1 levels. SA phenotypes were determined by high-resolution fluorescence microscopy in cultured primary CEC, and we used Thioflavin T to recognize RNA-G4s for fluorescence spectra. We found that cultured CEC from aged mice exhibited enhanced levels of SA phenotypes, and higher levels of CCN1 and G4 stabilization. In cultured CEC, CCN1 induced SA phenotypes, such as SA β-galactosidase activity, and double-strand DNA damage. Furthermore, CCN1 levels were upregulated by a G4 ligand, and a G-rich motif in the 3′-UTR of the Ccn1 mRNA was folded into a G4. In conclusion, we demonstrate that CCN1 can induce senescence in cultured primary CEC, and we provide evidence that G4 stabilization is a novel mechanism regulating the SASP component CCN1.

Adrenomedullin protects rat cerebral endothelial cells from oxidant damage in vitro

2005 ◽  
Vol 130 (1-2) ◽  
pp. 27-34 ◽  
Author(s):  
Lei Chen ◽  
Bela Kis ◽  
David W. Busija ◽  
Hiroshi Yamashita ◽  
Yoichi Ueta
Keyword(s):  
Endothelial Cells ◽  
Cerebral Endothelial Cells ◽  
Oxidant Damage

Abstract WMP82: Exosomes Derived From Cerebral Endothelial Cells of Young Adult Rats Reduced Cognitive Deficits in Aged Diabetic Rats

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Li Zhang ◽  
Michael Chopp ◽  
Chao Li ◽  
Quan Jiang ◽  
Guang Liang Ding ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cognitive Function ◽  
Young Adult ◽  
Cognitive Decline ◽  
Brain Slices ◽  
Amyloid Β ◽  
Adult Rats ◽  
Glymphatic System ◽  
Cerebral Endothelial Cells

Introduction: Diabetes mellitus (DM) is associated with cognitive decline and dementia in the elderly. The glymphatic system mediates clearance of the interstitial solutes in the brain by exchange of cerebrospinal and interstitial fluid (CSF and ISF). We recently demonstrated that DM in aged rat induces impairment of the glymphatic system and cognitive decline. Exosomes, membrane vesicles, mediate intercellular communication by transferring their cargo into recipient cells. The present study investigated whether cerebral endothelial exosomes (CEE) ameliorate glymphatic system impairment and improve cognitive function in aged DM rats. Methods and Results: DM was induced in male Wistar rats (13 months, n=48) by injection of nicotinamide and streptozotocin. Two months after DM, rats were treated with CEE (1x10 11 exosomes/rat, IV) twice a week for 4 weeks. Age matched DM and non-DM rats were used as controls. CEE were harvested from the cultured cerebral endothelial cells of health young adult rats. Exchanges of CSF and ISF were measured by intracisternal injection of fluorescent tracer, Texas Red-dextran (TR, 3kD). Confocal microscopic analysis of brain slices revealed a progressive slowdown of ISF clearance in the hippocampi, assessed by retention of TR starting at 2.5 fold at 2M (13±5 vs 5±3% of area) and increasing to 4 fold at 4M (21±4 vs 5±2%) of DM. Paravascular amyloid β (Aβ) accumulation was only detected at 4M of DM. The CEE treatment significantly (p<0.05) reduced TR retention (10±4%) at 4M of DM and also decreased Aβ accumulation (2±1 vs 6±2/mm 2 ) and parenchymal fibrin deposition (9±5 vs 23±5/mm 2 ) compared to untreated DM rats. Moreover, the CEE treatment significantly improved hippocampal related learning and memory measured by the Morris Water Maze and odor-based novelty recognition for olfactory memory, without altering the glucose level. In vitro, cerebral endothelial cells isolated from 2M DM rats exhibited substantial dysfunction as measured by capillary-like tube formation and cell migration, whereas incubation with the CEE substantially reversed endothelial dysfunction. Conclusions: The CEE treatment reduces DM-induced glymphatic and cerebral endothelial dysfunctions, leading to improvement of cognitive function in aged DM rats.

ECGF and heparin determine differentiation of cloned cerebral endothelial cells in vitro

1993 ◽  
Vol 20 (1) ◽  
pp. 33-43 ◽  
Author(s):  
Albert Amberger ◽  
Peter F. Lemkin ◽  
Peter Sonderegger ◽  
Hans C. Bauer
Keyword(s):  
Endothelial Cells ◽  
Cerebral Endothelial Cells

scholarly journals The Protective Effects of Preconditioning on Cerebral Endothelial Cells in Vitro

2003 ◽  
Vol 23 (11) ◽  
pp. 1348-1355 ◽  
Author(s):  
Anuska V Andjelkovic ◽  
Svetlana M Stamatovic ◽  
Richard F Keep
Keyword(s):  
Endothelial Cells ◽  
Lactate Dehydrogenase ◽  
Mouse Brain ◽  
Adhesion Molecule ◽  
Intercellular Adhesion ◽  
Intercellular Adhesion Molecule ◽  
Intercellular Adhesion Molecule 1 ◽  
Cerebral Endothelial Cells ◽  
Lactate Dehydrogenase Release

Ischemic preconditioning (PC) can markedly reduce ensuing ischemic damage. Although most attention has focused on the neuronal effects of PC, the authors have recently shown that ischemic PC reduces ischemia-induced cerebrovascular damage. In vivo, it is difficult to ascertain whether this is a direct cerebrovascular effect of PC. This study, therefore, examined whether cerebral endothelial cells can be preconditioned in vitro in the absence of other cell types. Experiments were performed on an immortalized mouse brain endothelial cell line or primary cultures of mouse brain microvessel endothelial cells. Cells were exposed to oxygen glucose deprivation (OGD) of either short duration, as a PC stimulus, or a long duration (5 hours) with or without reoxygenation to induce endothelial damage. Endothelial injury was assessed by measuring lactate dehydrogenase release and the expression of intercellular adhesion molecule-1 at the protein and mRNA levels. Experiments indicated that 1 hour of OGD was the optimal PC stimuli and that a 1 or 3 day interval was the optimal time interval between the PC stimulus and the injurious event. Preconditioned cells had less lactate dehydrogenase release during OGD (± reoxygenation) and reduced intercellular adhesion molecule-1 expression after OGD with reoxygenation. This study shows that cerebral endothelial cells can be directly preconditioned. The importance of this phenomenon in the overall effects of PC on the brain remains to be elucidated. Understanding the protective mechanisms elicited by PC may give insight into how to prevent ischemia-induced vascular damage (e.g., hemorrhagic transformation).

Interaction of T Lymphocytes with Cerebral Endothelial Cells in vitro

1991 ◽  
Vol 1 (2) ◽  
pp. 107-114 ◽  
Author(s):  
Hartmut Wekerle ◽  
Britta Engelhardt ◽  
Werner Risau ◽  
Richard Meyermann
Keyword(s):  
Endothelial Cells ◽  
T Lymphocytes ◽  
Cerebral Endothelial Cells

High-density lipoprotein and cerebral endothelial cells in vitro: Interactions and transport

1995 ◽  
Vol 50 (2) ◽  
pp. 271-273 ◽  
Author(s):  
H.E. De Vries ◽  
B. Breedveld ◽  
J. Kuiper ◽  
A.G. De Boer ◽  
Th.J.C. Van Berkel ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
High Density Lipoprotein ◽  
Density Lipoprotein ◽  
High Density ◽  
Cerebral Endothelial Cells ◽  
In Vitro Interactions

Characterization of the Scavenger Receptor on Bovine Cerebral Endothelial Cells In Vitro

1993 ◽  
Vol 61 (5) ◽  
pp. 1813-1821 ◽  
Author(s):  
H. E. Vries ◽  
J. Kuiper ◽  
A. G. Boer ◽  
Th. J. C. Berkel ◽  
D. D. Breimer
Keyword(s):  
Endothelial Cells ◽  
Scavenger Receptor ◽  
Cerebral Endothelial Cells

scholarly journals Selective Astrocytic Endothelin-1 Overexpression Contributes to Dementia Associated with Ischemic Stroke by Exaggerating Astrocyte-Derived Amyloid Secretion

2015 ◽  
Vol 35 (10) ◽  
pp. 1687-1696 ◽  
Author(s):  
Victor KL Hung ◽  
Patrick KK Yeung ◽  
Angela KW Lai ◽  
Maggie CY Ho ◽  
Amy CY Lo ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cognitive Deficits ◽  
In Vitro Study ◽  
Artery Occlusion ◽  
Spatial Learning And Memory ◽  
Dependent Manner ◽  
Endothelin 1 ◽  
Endothelin B

Endothelin-1 (ET-1) is synthesized by endothelial cells and astrocytes in stroke and in brains of Alzheimer's disease patients. Our transgenic mice with ET-1 overexpression in the endothelial cells (TET-1) showed more severe blood–brain barrier (BBB) breakdown, neuronal apoptosis, and glial reactivity after 2-hour transient middle cerebral artery occlusion (tMCAO) with 22-hour reperfusion and more severe cognitive deficits after 30 minutes tMCAO with 5 months reperfusion. However, the role of astrocytic ET-1 in contributing to poststroke cognitive deficits after tMCAO is largely unknown. Therefore, GET-1 mice were challenged with tMCAO to determine its effect on neurologic and cognitive deficit. The GET-1 mice transiently displayed a sensorimotor deficit after reperfusion that recovered shortly, then more severe deficit in spatial learning and memory was observed at 3 months after ischemia compared with that of the controls. Upregulation of TNF- a, cleaved caspase-3, and Thioflavin-S-positive aggregates was observed in the ipsilateral hemispheres of the GET-1 brains as early as 3 days after ischemia. In an in vitro study, ET-1 overexpressing astrocytic cells showed amyloid secretion after hypoxia/ischemia insult, which activated endothelin A (ETA) and endothelin B (ETB) receptors in a PI3K/AKT-dependent manner, suggesting role of astrocytic ET-1 in dementia associated with stroke by astrocyte-derived amyloid production.

Sign in / Sign up

Export Citation Format

Share Document