Hydrogen peroxide derived from hepatocytes induces sinusoidal endothelial cell apoptosis in perfused hypoxic rat liver

Motoyama, Satoru; Minamiya, Yoshihiro; Saitô, Satoshi; Saito, Reijiro; Matsuzaki, Ikuo; Abo, Shichisaburo; Inaba, Hideo; Enomoto, Katsuhiko; Kitamura, Michihiko

doi:10.1016/s0016-5085(98)70643-2

Cited by 59 publications

(43 citation statements)

References 28 publications

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“…In vessels treated with catalase, the fluorescence intensities in endothelial cells and VSMCs were unaltered after exposure to intraluminal flow (Figures 2e through 2h). Summary data showing the change in endothelial fluorescence intensity to shear stress is shown in Figure 2 To more directly determine the role of H 2 O 2 in FID, electron microscopy was conducted to detect cerium deposition, which is produced by the reaction of H 2 O 2 with cerium ions, 25,26 in layers of vessels exposed to shear stress. In vessels without exposure to shear stress, few cerium depositions were observed in the intima (Figures 3A and 3D).…”

Section: Resultsmentioning

confidence: 99%

“…To estimate and localize shear stress-induced H 2 O 2 production, histochemical electron microscopy was performed with cerium chloride, 25,26 a staining method that allows the specific visualization of H 2 O 2 production in tissues. Briefly, three vessels were isolated from each subject and incubated in 10 mmol/L Tris-maleate saline buffer (pH 7.4) containing 5.5 mmol/L glucose, 7% sucrose, and 3-amino-1H-1,2,4-triazole (10 Ϫ2 mol/L) for 30 minutes.…”

Section: Detection Of Extracellular H 2 O 2 Release With Electron Micmentioning

confidence: 99%

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Role for Hydrogen Peroxide in Flow-Induced Dilation of Human Coronary Arterioles

Miura

Bosnjak

Ning

et al. 2003

Circulation Research

403

381

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Abstract-Flow-induced dilation (FID) is dependent largely on hyperpolarization of vascular smooth muscle cells (VSMCs) in human coronary arterioles (HCA) from patients with coronary disease. Animal studies show that shear stress induces endothelial generation of hydrogen peroxide (H 2 O 2 ), which is proposed as an endothelium-derived hyperpolarizing factor (EDHF). We tested the hypothesis that H 2 O 2 contributes to FID in HCA. Arterioles (135Ϯ7 m, nϭ71) were dissected from human right atrial appendages at the time of cardiac surgery and cannulated with glass micropipettes. Changes in internal diameter and membrane potential of VSMCs to shear stress, H 2 O 2 , or to papaverine were recorded with videomicroscopy. In some vessels, endothelial H 2 O 2 generation to shear stress was monitored directly using confocal microscopy with 2Ј,7Ј-dichlorofluorescin diacetate (DCFH) or using electron microscopy with cerium chloride. Catalase inhibited FID (%max dilation; 66Ϯ8 versus 25Ϯ7%; PϽ0.05, nϭ6), whereas dilation to papaverine was unchanged. Shear stress immediately increased DCFH fluorescence in the endothelial cell layer, whereas treatment with catalase abolished the increase in fluorescence. Electron microscopy with cerium chloride revealed shear stress-induced increase in cerium deposition in intimal area surrounding endothelial cells. Exogenous H 2 O 2 dilated (%max dilation; 97Ϯ1%, ED 50 ; 3.0Ϯ0.7ϫ10 Ϫ5 mol/L) and hyperpolarized HCA. Dilation to H 2 O 2 was reduced by catalase, 40 mmol/L KCl, or charybdotoxin plus apamin, whereas endothelial denudation, deferoxamine, 1H-1,2,4 -oxadiazole-[4,3-a]quinoxalin-1-one, or glibenclamide had no effect. These data provide evidence that shear stress induces endothelial release of H 2 O 2 and are consistent with the idea that H 2 O 2 is an EDHF that contributes to FID in HCA from patients with heart disease. The full text of this article is available at http://www.circresaha.org. (Circ Res. 2003;92:e31-e40.)Key Words: human Ⅲ coronary microcirculation Ⅲ flow-induced dilation Ⅲ hydrogen peroxides P hysiologically, shear stress plays a critical role in the regulation of vascular tonus and vascular homeostasis, contributing to the maintenance of tissue perfusion and vascular integrity. Shear stress-induced release of nitric oxide (NO) from endothelial cells is widely recognized as one of the most important and common mechanisms for shear-induced vasomotion. For example, flow-induced release of NO is responsible for the mediation of flow-induced vasodilation (FID). [1][2][3] Animal studies have reported that the contribution of NO to FID is reduced as oxidative stress increases in the presence of risk factors for cardiovascular disease such as hypercholesterolemia 4 and hypertension. 5 In humans, in vivo and in vitro studies have demonstrated that relaxant factor(s) other than NO compensate to maintain FID when NO availability is reduced. 6,7 We recently reported that FID is mediated largely by endothelium-derived hyperpolarizing factor (EDHF) in human coronary arterioles (HCAs...

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Section: Resultsmentioning

confidence: 99%

Section: Detection Of Extracellular H 2 O 2 Release With Electron Micmentioning

confidence: 99%

Role for Hydrogen Peroxide in Flow-Induced Dilation of Human Coronary Arterioles

Miura

Bosnjak

Ning

et al. 2003

Circulation Research

403

381

View full text Add to dashboard Cite

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“…Today it is known that hepatocyte hypoxia through ATP depletion and hydrogen peroxide production induces sinusoidal endothelial cell apoptosis (Motoyama et al 1998). It is plausible to presume that the initial hepatocyte injury in conjunction with the direct toxic injury of nonparenchymal cells induces apoptotic cell death in nonparenchymal liver cells.…”

Section: Discussionmentioning

confidence: 99%

Time-course of cadmium-induced acute hepatotoxicity in the rat liver: the role of apoptosis

Tzirogiannis¹,

Panoutsopoulos²,

Demonakou

et al. 2003

Archives of Toxicology

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Exposure to toxic metals and pollutants is a major environmental problem. Cadmium is a metal causing acute hepatic injury but the mechanism of this phenomenon is poorly understood. In the present study, we investigated the mechanism and time-course of cadmium-induced liver injury in rats, with emphasis being placed on apoptosis in parenchymal and nonparenchymal liver cells. Cadmium (3.5 mg/kg body weight) was injected intraperitoneally and the rats were killed 0, 9, 12, 16, 24, 48 and 60 h later. The extent of liver injury was evaluated for necrosis, apoptosis, peliosis, mitoses and inflammatory infiltration in hematoxylin-eosin-stained liver sections, and by assaying serum enzyme activities. The number of cells that died via apoptosis was quantified by TUNEL assay. The identification of nonparenchymal liver cells and activated Kupffer cells was performed histochemically. Liver regeneration was evaluated by assaying the activity of liver thymidine kinase and by the rate of 3H-thymidine incorporation into DNA. Both cadmium-induced necrotic cell death and parenchymal cell apoptosis showed a biphasic elevation at 12 and 48 h and peaked at 48 and 12 h, respectively. Nonparenchymal cell apoptosis peaked at 48 h. Peliosis hepatis, another characteristic form of liver injury, was first observed at 16 h and, at all time points, closely correlated with the apoptotic index of nonparenchymal liver cells, where the lesion was also maximial at 48 h. Kupffer cell activation and neutrophil infiltration were minimal for all time points examined. Based on thymidine kinase activity, liver regeneration was found to discern a classic biphasic peak pattern at 12 and 48 h. It was very interesting to observe that cadmium-induced liver injury did not involve inflammation at any time point. Apoptosis seems to be a major mechanism for the removal of damaged cells, and constitutes the major type of cell death in nonparenchymal liver cells. Apoptosis of nonparenchymal cells is the basis of the pathogenesis of peliosis hepatis. The first peaks of necrosis and parenchymal cell apoptosis seem to evolve as a result of direct cadmium effects whereas the latter ones result from ischemia.

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“…Neutrophils, macrophages (including KCs), as well as hepatocytes and liver endothelial cells can produce ROM upon activation [43, 44, 45, 46]. Also, vascular endothelial cells are capable of releasing H 2 O 2 [26], and endogenously produced H 2 O 2 has been found to stimulate fluid phase endocytosis of fluorescent dextran (7,000 daltons) by vascular endothelial cells [47].…”

Section: Discussionmentioning

confidence: 99%

IgG Immune Complex Binding to and Activation of Liver Cells

Johansson

Sundqvist

2000

Int Arch Allergy Immunol

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Background/Aims: The aim was to study IgG immune complex (IC) binding to isolated hepatocytes, Kupffer cells (KCs) and sinusoidal endothelial cells (SECs). Further, we wished to analyze the capacity of IgG ICs to induce release of reactive oxygen metabolites by the IC-binding liver cells. Methods: ICs were formed between ¹²⁵I-tyramine-cellobiose-labelled dinitrophenyl-conjugated human serum albumin (¹²⁵I-TC-DNP₁₀HSA) and polyclonal rabbit IgG antibodies. Binding of ICs to different rat liver cells in suspension was studied at 4°C. Production of reactive oxygen metabolites was measured by luminol-enhanced chemiluminescence at 37°C. Results: IgG mediated binding of ¹²⁵I-TC-DNP₁₀HSA to both KCs and SECs, but not to hepatocytes. The binding showed saturation kinetics and was blocked by an excess of unlabelled IgG-ICs. IgG-ICs activated KCs, but not SECs, to a chemiluminescence response. Conclusions: Both KCs and SECs bind IgG-ICs in vitro, probably via Fc receptor interaction. IgG-ICs activate KCs to produce reactive oxygen metabolites. The binding of IgG-ICs to isolated hepatocytes is small.

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Hydrogen peroxide derived from hepatocytes induces sinusoidal endothelial cell apoptosis in perfused hypoxic rat liver

Cited by 59 publications

References 28 publications

Role for Hydrogen Peroxide in Flow-Induced Dilation of Human Coronary Arterioles

Role for Hydrogen Peroxide in Flow-Induced Dilation of Human Coronary Arterioles

Time-course of cadmium-induced acute hepatotoxicity in the rat liver: the role of apoptosis

IgG Immune Complex Binding to and Activation of Liver Cells

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