The Protective Effects of Dexmedetomidine against Hypoxia/Reoxygenation-Induced Inflammatory Injury and Permeability in Brain Endothelial Cells Mediated by Sigma-1 Receptor

2021 ◽  
Author(s):  
Qin Zhao ◽  
Shoushui Yu ◽  
Yong Ling ◽  
Shiyuan Hao ◽  
Jia Liu
Keyword(s):  
Endothelial Cells ◽  
Protective Effects ◽  
Brain Endothelial Cells ◽  
Inflammatory Injury ◽  
Sigma 1 Receptor ◽  
Sigma 1 ◽  
Hypoxia Reoxygenation

Abstract 113: Regulation Of Aortic Vasodilation By Sigma-1 Receptor Stimulation In Ovariectomized And Pressure Overloaded Rats.

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Hideaki Tagashira ◽  
Takayuki Matsumoto ◽  
Kumiko Taguchi ◽  
Tsuneo Kobayashi ◽  
Kohji Fukunaga
Keyword(s):  
Endothelial Cells ◽  
Vascular Endothelial Cells ◽  
Pressure Overload ◽  
Endothelial Injury ◽  
Vascular Endothelial ◽  
Aortic Banding ◽  
Descending Aorta ◽  
Sigma 1 Receptor ◽  
Ovx Rats ◽  
Sigma 1

Objective: We previously reported that sigma-1 receptor ( σ 1 R ) expression in the thoracic aorta decreased after pressure overload (PO) induced by abdominal aortic banding in ovariectomized (OVX) rats. Here, we asked whether stimulation of σ 1 R with the selective agonist SA4503 elicits functional recovery of aortic vasodilation and constriction following vascular injury in OVX rats with PO. Methods: SA4503 (0.3-1.0 mg kg -1 ) and NE-100 (an σ 1 R antagonist, 1.0 mg kg -1 ) were administered orally for 4 weeks (once daily) to OVX-PO rats, starting from the onset of aortic banding. Vascular functions of isolated descending aorta were measured following phenylephrine (PE)- or endothelin-1 (ET-1)-induced vasoconstriction and acetylcholine (ACh)- or clonidine-induced vasodilation. Results: σ 1 R expression in aortic smooth muscle and endothelial cells decreased significantly 4 weeks after PO in OVX rats (vs. Sham or OVX only group). SA4503 administration rescued PO-induced σ 1 R decreases in the descending aorta. SA4503 treatment also rescued PO-induced impairments in ACh- and clonidine-induced vasodilation without affecting PE- and ET-1-induced vasoconstriction. Ameliorated ACh- and clonidine-induced vasodilation was closely associated with increased Akt activity and in turn endothelial nitric oxide synthase (eNOS) phosphorylation. SA4503-mediated improvement of vasodilation was blocked by NE-100 treatment. Conclusions: σ 1 R is downregulated following PO-induced endothelial injury in OVX rats. The selective σ 1 R agonist SA4503 rescues impaired endothelium-dependent vasodilation in the aorta from OVX-PO rats through σ 1 R stimulation, enhancing eNOS-cGMP signaling in vascular endothelial cells. These observations encourage development of novel therapeutics targeting σ 1 R to prevent vascular endothelial injury in postmenopausal woman.

scholarly journals Nrf2-regulated redox signaling in brain endothelial cells adapted to physiological oxygen levels: Consequences for sulforaphane mediated protection against hypoxia-reoxygenation

Redox Biology ◽  
2020 ◽  
Vol 37 ◽  
pp. 101708
Author(s):  
Gabriela Warpsinski ◽  
Matthew J. Smith ◽  
Salil Srivastava ◽  
Thomas P. Keeley ◽  
Richard C.M. Siow ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Redox Signaling ◽  
Brain Endothelial Cells ◽  
Oxygen Levels ◽  
Hypoxia Reoxygenation

scholarly journals Estrogen-Receptor-Mediated Protection of Cerebral Endothelial Cell Viability and Mitochondrial Function after Ischemic Insult in vitro

2009 ◽  
Vol 30 (3) ◽  
pp. 545-554 ◽  
Author(s):  
Jiabin Guo ◽  
Diana N Krause ◽  
James Horne ◽  
John H Weiss ◽  
Xuejun Li ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Estrogen Receptor ◽  
Endothelial Cell ◽  
Cell Viability ◽  
Mitochondrial Function ◽  
Protective Effects ◽  
Brain Endothelial Cells ◽  
Ischemic Insult ◽  
Mitochondrial Superoxide

Protective effects of estrogen against experimental stroke and neuronal ischemic insult are well-documented, but it is not known whether estrogen prevents ischemic injury to brain endothelium, a key component of the neurovascular unit. Increasing evidence indicates that estrogen exerts protective effects through mitochondrial mechanisms. We previously found 17β-estradiol (E2) to improve mitochondrial efficiency and reduce mitochondrial superoxide in brain blood vessels and endothelial cells. Thus we hypothesized E2 will preserve mitochondrial function and protect brain endothelial cells against ischemic damage. To test this, an in vitro ischemic model, oxygen-glucose deprivation (OGD)/reperfusion, was applied to immortalized mouse brain endothelial cells (bEnd.3). OGD/reperfusion-induced cell death was prevented by long-term (24, 48 h), but not short-term (0.5, 12 h), pretreatment with 10 nmol/L E2. Protective effects of E2 on endothelial cell viability were mimicked by an estrogen-receptor (ER) agonist selective for ERα (PPT), but not by one selective for ERβ (DPN). In addition, E2 significantly decreased mitochondrial superoxide and preserved mitochondrial membrane potential and ATP levels in early stages of OGD/reperfusion. All of the E2 effects were blocked by the ER antagonist, ICI-182,780. These findings indicate that E2 can preserve endothelial mitochondrial function and provide protection against ischemic injury through ER-mediated mechanisms.

Protective effects of carnosine against malondialdehyde-induced toxicity towards cultured rat brain endothelial cells

1997 ◽  
Vol 238 (3) ◽  
pp. 135-138 ◽  
Author(s):  
Alan R Hipkiss ◽  
Jane E Preston ◽  
David T.M Himswoth ◽  
Viki C Worthington ◽  
N.Joan Abbot
Keyword(s):  
Endothelial Cells ◽  
Rat Brain ◽  
Protective Effects ◽  
Brain Endothelial Cells ◽  
Rat Brain Endothelial Cells

scholarly journals Cocaine inhibits store-operated Ca2+ entry in brain microvascular endothelial cells: critical role for sigma-1 receptors

2015 ◽  
Vol 473 (1) ◽  
pp. 1-5 ◽  
Author(s):  
G. Cristina Brailoiu ◽  
Elena Deliu ◽  
Linda M. Console-Bram ◽  
Jonathan Soboloff ◽  
Mary E. Abood ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Rat Brain ◽  
Critical Role ◽  
Calcium Entry ◽  
Microvascular Endothelial Cells ◽  
Brain Microvascular Endothelial Cells ◽  
Sigma 1 Receptor ◽  
Store Operated Calcium Entry ◽  
Sigma 1 ◽  
Microvascular Endothelial

We provide evidence that cocaine induces sigma-1 receptor-mediated inhibition of store-operated calcium entry (SOCE) in rat brain microvascular endothelial cells. Thus, we reveal sigma-1 receptors as SOCE blockers, adding novel insight regarding endothelial effects of cocaine and endogenous SOCE modulation.

scholarly journals Protective Effects of Scutellarin on Human Cardiac Microvascular Endothelial Cells against Hypoxia-Reoxygenation Injury and Its Possible Target-Related Proteins

2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
Meina Shi ◽  
Yingting Liu ◽  
Lixing Feng ◽  
Yingbo Cui ◽  
Yajuan Chen ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Expression Profiles ◽  
Interaction Network ◽  
Treated Group ◽  
Microvascular Endothelial Cells ◽  
Protective Effects ◽  
Microvascular Endothelial ◽  
Related Proteins ◽  
Cardiac Microvascular Endothelial Cells ◽  
Hypoxia Reoxygenation

Scutellarin (SCU) is one of the main components of traditional Chinese medicine plantErigeron breviscapus (Vant.)Hand.-Mazz. In this paper, we studied the protective effects of SCU on human cardiac microvascular endothelial cells (HCMECs) against hypoxia-reoxygenation (HR) injury and its possible target-related proteins. Results of MTT assay showed that pretreatment of SCU at doses of 1, 5, and 10 μM for 2 h could significantly inhibit the decrease in cell viability of HCMECs induced by HR injury. Subcellular fractions of cells treated with vehicle control, 1 μM SCU, HR injury, or 1 μM SCU + HR injury were separated by ultracentrifugation. The protein expression profiles of cytoplasm and membrane/nuclei fractions were checked using protein two-dimensional electrophoresis (2-DE). Proteins differentially expressed between control and SCU-treated group, control and HR group, or HR and SCU + HR group were identified using mass spectrometry (MS/MS). Possible interaction network of these target-related proteins was predicted using bioinformatic analysis. The influence of SCU on the expression levels of these proteins was confirmed using Western blotting assay. The results indicated that proteins such as p27BBP protein (EIF6), heat shock 60 kDa protein 1 (HSPD1), and chaperonin containing TCP1 subunit 6A isoform (CCT6A) might play important roles in the effects of SCU.

Nitric Oxide Contributes to Hypoxia-Reoxygenation-Induced P-Glycoprotein Expression in Rat Brain Endothelial Cells

2011 ◽  
Vol 31 (7) ◽  
pp. 1103-1111 ◽  
Author(s):  
Samantha J. Robertson ◽  
Ruth Mokgokong ◽  
Katarzyna D. Kania ◽  
Anne-Sophie Guedj ◽  
Stephen B. Hladky ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cells ◽  
Rat Brain ◽  
Brain Endothelial Cells ◽  
P Glycoprotein ◽  
Rat Brain Endothelial Cells ◽  
Hypoxia Reoxygenation

Hypoxia-reoxygenation increases O2-. efflux which injures endothelial cells by an extracellular mechanism

1996 ◽  
Vol 270 (3) ◽  
pp. H945-H950 ◽  
Author(s):  
L. S. Terada
Keyword(s):  
Endothelial Cells ◽  
Xanthine Oxidase ◽  
Anion Channel ◽  
Disulfonic Acid ◽  
Iron Chelators ◽  
Protective Effects ◽  
Nitroblue Tetrazolium Reduction ◽  
Cytochrome C Reduction ◽  
Reoxygenation Injury ◽  
Hypoxia Reoxygenation

The mechanisms by which superoxide anion (O2-.) injures reoxygenated vascular cells are not clearly understood. We hypothesized that O2-. formed in an intracellular compartment during reoxygenation may egress through plasmalemmal anion channels and mediate injury from an extracellular site. Bovine pulmonary artery endothelial cells (EC) kept hypoxic for 48 h had increased release of preloaded 51Cr upon reoxygenation. Evidence for an extracellular site of injury was the following. First, decreasing extracellular O2-. levels (measured by cytochrome c reduction) with the anion channel blocker 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) leads to decreased 51Cr leak. In contrast to its effect on extracellular O2-., DIDS increased intracellular O2-. levels (measured by nitroblue tetrazolium reduction) following reoxygenation. Second, treatment with exogenous superoxide dismutase (SOD), while having no significant effect on intracellular O2-. levels, also decreased 51Cr leak. Furthermore, cotreatment of EC with DIDS did not abrogate the protective effects of exogenous SOD, suggesting that SOD decreased injury by decreasing extracellular and not intracellular O2-. Finally, exposure of EC to extracellularly generated O2-. (xanthine oxidase/hypoxanthine system) caused injury, which was decreased by SOD but not by blockade of O2-. entry with DIDS. The mechanism by which O2-. injures EC may involve generation of .OH by surface-associated iron, since iron chelators and .OH scavengers of varying membrane permeability all decreased 51Cr release to a similar extent. Furthermore, the iron chelators and .OH scavengers also decreased EC 51Cr leak following exposure to exogenous xanthine oxidase/hypoxanthine but not following exposure to a O2(-.)-independent agent (A23187). We conclude that hypoxia-reoxygenation injures EC in a manner that is at least in part dependent on the efflux of O2-. into the extracellular space. Endogenous and exogenous strategies for protection against reoxygenation injury must target extracellular O2-. as a potentially harmful species.

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