H2O2 induces paracellular permeability of porcine brain-derived microvascular endothelial cells by activation of the p44/42 MAP kinase pathway

Fischer, Silvia; Wiesnet, Marion; Renz, D.; Schäper, Wolfgang

doi:10.1016/j.ejcb.2005.03.002

Cited by 137 publications

(93 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Inhibitors of the p42/44-MAPK and the JNK did not prevent the CRP-dependent loss of barrier integrity. This observations is well in line with studies from the cardiovascular circulation demonstrating a CRP-induced p38-MAPK-dependent increase of cytokines and cell adhesion molecules in human coronary artery endothelial cells 34 and a p38-MAPK-dependent loss of serotonin-induced dilation of porcine coronary arterioles. 26 We and others demonstrated a pivotal role of oxidative stress in BBB disruption.…”

Section: Discussionsupporting

confidence: 79%

Mechanisms of C-Reactive Protein-Induced Blood–Brain Barrier Disruption

Kuhlmann

Librizzi

Closhen³

et al. 2009

Stroke

107

View full text Add to dashboard Cite

Background and Purpose-Increased mortality after stroke is associated with brain edema formation and high plasma levels of the acute phase reactant C-reactive protein (CRP). The aim of this study was to examine whether CRP directly affects blood-brain barrier stability and to analyze the underlying signaling pathways. Methods-We used a cell coculture model of the blood-brain barrier and the guinea pig isolated whole brain preparation. Results-We could show that CRP at clinically relevant concentrations (10 to 20 g/mL) causes a disruption of the blood-brain barrier in both approaches. The results of our study further demonstrate CRP-induced activation of surface Fc␥ receptors CD16/32 followed by p38-mitogen-activated protein kinase-dependent reactive oxygen species formation by the NAD(P)H-oxidase. The resulting oxidative stress increased myosin light chain kinase activity leading to an activation of the contractile machinery. Blocking myosin light chain phosphorylation prevented the CRP-induced blood-brain barrier breakdown and the disruption of tight junctions. Conclusions-Our data identify a previously unrecognized mechanism linking CRP and brain edema formation and present a signaling pathway that offers new sites of therapeutic intervention.

show abstract

Section: Discussionsupporting

confidence: 79%

Mechanisms of C-Reactive Protein-Induced Blood–Brain Barrier Disruption

Kuhlmann

Librizzi

Closhen³

et al. 2009

Stroke

107

View full text Add to dashboard Cite

show abstract

“…Hydroxyl radicals derived from superoxide anions have been reported as a key factor in increased vascular permeability produced by ischemia and systemic infusion or local superfusion of HX/XO (7,28,29 ] i and permeability indicate that these two ROS may trigger signaling pathways or evoke cellular damage via different cellular mechanisms. Currently, in vitro studies indicate that endothelial gap formation, the disruption of adhesion proteins, and the changes in cytoskeleton arrangements are the mechanisms for ROS-induced endothelial barrier dysfunction, which are similar to those reported in inflammatory mediator-induced permeability increases (1,9,12,17,20,21,36). Whether different cellular mechanisms are responsible for such distinct patterns of permeability increases in intact microvessels remains to be determined.…”

Section: Superoxide Induced Immediate and Transient Increases In Endomentioning

confidence: 78%

Calcium influx-dependent differential actions of superoxide and hydrogen peroxide on microvessel permeability

Zhou¹,

Wen²,

Dong³

et al. 2009

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

He P. Calcium influxdependent differential actions of superoxide and hydrogen peroxide on microvessel permeability. Am J Physiol Heart Circ Physiol 296: H1096 -H1107, 2009. First published February 6, 2009 doi:10.1152/ajpheart.01037.2008.-Our previous study demonstrated that reactive oxygen species (ROS) released from activated blood cells contribute significantly to the increased microvessel permeability during inflammation. This study aims to define the individual roles of hydrogen peroxide (H 2O2) and superoxide in ROSinduced increases in permeability and endothelial intracellular Ca 2ϩ concentration ([Ca 2ϩ ]i) in individually perfused rat mesenteric venules. Microvessel permeability was determined by measuring hydraulic conductivity (L p). Endothelial [Ca 2ϩ ]i was measured in fura-2 AM-loaded microvessels. Perfusing microvessels with superoxide generated by hypoxanthine and xanthine oxidase (HX/XO) induced immediate and transient increases in L p. The mean peak value, which occurred within 5 min of HX/XO exposure, was 4.3 Ϯ 0.6 times that of the control. In contrast, the perfusion of H 2O2 (100 and 500 M) caused no immediate increases in L p. A significant Lp increase, 3.6 Ϯ 0.6 times the control value, occurred 30 min after the perfusion of H 2O2 at 500 M. The perfusion of H2O2 at 100 or 500 M for 1 h increased L p to 6.6 Ϯ 0.9 and 11.3 Ϯ 3.6 times the control value, respectively. The increased endothelial [Ca 2ϩ ]i in HX/XO or H 2O2 perfused vessels was correlated with the time course of the increases in L p. Inhibiting Ca 2ϩ influx by LaCl3 prevented the permeability increase induced by HX/XO or H 2O2. These results demonstrated differential actions of superoxide and H 2O2 on microvessel permeability and endothelial [Ca 2ϩ ]i. Superoxide-induced permeability increases were immediate and transient, whereas H 2O2-induced permeability increases were progressive, demonstrating concentration and time dependence. Ca 2ϩ influx plays an essential role in both superoxide and H 2O2-induced permeability increases. hydraulic conductivity; reactive oxygen species; endothelial calcium imaging REACTIVE OXYGEN species (ROS) contribute to various pathological conditions such as inflammation and ischemic reperfusion as well as atherosclerosis. A major source of ROS in the vascular system is from activated blood cells during respiratory burst. Our previous studies demonstrated that the ROS released from formyl Met-Leu-Phe-OH (fMLP)-stimulated neutrophils, either in suspension or from adherent leukocytes, cause immediate and transient increases in microvessel permeability (37,38). Prolonged permeability increases were observed with leukocyte/platelet aggregate adhesion to microvessel walls after initial endothelial cell activation by inflammatory mediators and endothelial gap formation (15). However, whether superoxide or hydrogen peroxide (H 2 O 2 ) converted from superoxide is the main species causing the increases in permeability under such experimental conditions remains unknown. Currently, most ROS-induced si...

show abstract

“…TJ proteins have also been examined using in vitro models of BBB. Hypoxiareoxygenation, hydrogen peroxide, and other oxidants were shown to alter occludin, ZO-1, and ZO-2 in brain-derived microvascular endothelial cells [17,27,28]. BBB permeability is regulated by monocyte chemoattractant protein-1, which changes the cellular distribution of these TJ proteins [29].…”

Section: Discussionmentioning

confidence: 99%

Altered Expression of Zonula Occludens-2 Precedes Increased Blood–Brain Barrier Permeability in a Murine Model of Fulminant Hepatic Failure

Shimojima

Eckman

McKinney

et al. 2008

Journal of Investigative Surgery

View full text Add to dashboard Cite

Brain edema secondary to increased blood-brain barrier (BBB) permeability is a lethal complication in fulminant hepatic failure (FHF). Intact tight junctions (TJ) between brain capillary endothelial cells are critical for normal BBB function. However, the role of TJ in FHF has not been explored. We hypothesized that alterations in the composition of TJ proteins would result in increased BBB permeability in FHF. In this study, FHF was induced in C57BL/6J mice by using azoxymethane. BBB permeability was assessed with sodium fluorescein. Expression of TJ proteins was determined by Western blot, and their cellular distribution was examined using immunofluorescent microscopy. Comatose FHF mice had significant cerebral sodium fluorescein extravasation compared with control and precoma FHF mice, indicating increased BBB permeability. Western blot analysis showed a significant decrease in zonula occludens (ZO)-2 expression starting in the precoma stage. Immunofluorescent microscopy showed a significantly altered distribution pattern of ZO-2 in

show abstract

H2O2 induces paracellular permeability of porcine brain-derived microvascular endothelial cells by activation of the p44/42 MAP kinase pathway

Cited by 137 publications

References 55 publications

Mechanisms of C-Reactive Protein-Induced Blood–Brain Barrier Disruption

Mechanisms of C-Reactive Protein-Induced Blood–Brain Barrier Disruption

Calcium influx-dependent differential actions of superoxide and hydrogen peroxide on microvessel permeability

Altered Expression of Zonula Occludens-2 Precedes Increased Blood–Brain Barrier Permeability in a Murine Model of Fulminant Hepatic Failure

Contact Info

Product

Resources

About