Nitric Oxide Protects Macrophages from Hydrogen Peroxide-Induced Apoptosis by Inducing the Formation of Catalase

Yoshioka, Yasuhiro; Kitao, Toshio; Kishino, Takashi; Yamamuro, Akiko; Maeda, Shin

doi:10.4049/jimmunol.176.8.4675

Cited by 53 publications

(44 citation statements)

References 63 publications

(45 reference statements)

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“…To assess the proliferation/viability of endothelial cells, the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay was also used as previously described. 19 For proliferation, cells were pulse labeled with 10-mol/L BrdU (Sigma) for 6 hours at 37°C. Cells were fixed in 4% paraformaldehyde for 10 minutes, followed by a denaturation step in 0.5N hydrochloride for 10 minutes and a neutralization step with 0.1-mol/L sodium borate for 10 minutes.…”

Section: Proliferation Assaysmentioning

confidence: 99%

Apelin Is a Crucial Factor for Hypoxia-Induced Retinal Angiogenesis

Kasai

Ishimaru²,

Kinoshita³

et al. 2010

ATVB

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Objective-To investigate the role of endogenous apelin in pathological retinal angiogenesis. Methods and Results-The progression of ischemic retinal diseases, such as diabetic retinopathy, is closely associated with pathological retinal angiogenesis, mainly induced by vascular endothelial growth factor (VEGF) and erythropoietin. Although antiangiogenic therapies using anti-VEGF drugs are effective in treating retinal neovascularization, they show a transient efficacy and cause general adverse effects. New therapeutic target molecules are needed to resolve these issues. It was recently demonstrated that the apelin/APJ system, a newly deorphanized G protein-coupled receptor system, is involved in physiological retinal vascularization. Retinal angiography and mRNA expression were examined during hypoxia-induced retinal angiogenesis in a mouse model of oxygen-induced retinopathy. Compared with age-matched control mice, retinal apelin expression was dramatically increased during the hypoxic phase in oxygen-induced retinopathy model mice. APJ was colocalized in proliferative cells, which were probably endothelial cells of the ectopic vessels in the vitreous body. Apelin deficiency hardly induced hypoxia-induced retinal angiogenesis despite the upregulation of VEGF and erythropoietin mRNA in oxygen-induced retinopathy model mice. Apelin small and interfering RNA suppressed the proliferation of endothelial cells independent of the VEGF/VEGF receptor 2 signaling pathway. Conclusion-These results suggest that apelin is a prerequisite factor for hypoxia-induced retinal angiogenesis. Key Words: angiogenesis Ⅲ VEGF Ⅲ apelin Ⅲ retinopathy T he progression of ischemic retinal diseases, such as diabetic retinopathy, is closely associated with pathological retinal angiogenesis, which is mainly induced by vascular endothelial growth factor (VEGF) 1 and erythropoietin (Epo). 2 Antiangiogenic therapies targeting these factors are effective in treating proliferative diabetic retinopathy. 3,4 However, these therapies show a transient efficacy and cause the general adverse effects. 5 Furthermore, elevated VEGF levels do not necessarily correlate with pathological retinal angiogenesis in patients with diabetic maculopathy. 6 This suggests that the entire process of pathological retinal angiogenesis includes more than just upregulation of VEGF expression. Therefore, finding other factors involved in pathological retinal angiogenesis is important.The apelin/apelin receptor (APJ) system is a newly deorphanized G protein-coupled receptor system. 7 Recently, much attention has been focused on the possible roles of the apelin/APJ system in vascular pathophysiology. 8,9 APJ is expressed in endothelial cells at the leading edge of vessels during early embryogenesis; and apelin, in combination with VEGF, induces the proliferation and assembly of endothelial cells. 10 Moreover, we demonstrated a retardation of physiological retinal vascular development during the early postnatal period and a reduced angiogenic response to VEGF in apelin-knockout...

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Section: Proliferation Assaysmentioning

confidence: 99%

Apelin Is a Crucial Factor for Hypoxia-Induced Retinal Angiogenesis

Kasai

Ishimaru²,

Kinoshita³

et al. 2010

ATVB

Self Cite

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“…Regarding the lysosome-associated cell death induced by oxidative stress, previous studies revealed that Fe ions within lysosomes catalyze the peroxidation of H 2 O 2 through Fenton's reaction and produce highly reactive oxygen radicals (30,31,42,49,50). The resultant oxygen radicals damage and destabilize lysosomal membranes (30,31,42,49,50).…”

Section: Discussionmentioning

confidence: 99%

“…The resultant oxygen radicals damage and destabilize lysosomal membranes (30,31,42,49,50). Thus, Fe ions within lysosomes play an important role in H 2 O 2 -induced cell death (30,31,42,49,50).…”

Section: Discussionmentioning

confidence: 99%

Streptococcus oralis Induces Lysosomal Impairment of Macrophages via Bacterial Hydrogen Peroxide

et al. 2016

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c Streptococcus oralis, an oral commensal, belongs to the mitis group of streptococci and occasionally causes opportunistic infections, such as bacterial endocarditis and bacteremia. Recently, we found that the hydrogen peroxide (H 2 O 2 ) produced by S. oralis is sufficient to kill human monocytes and epithelial cells, implying that streptococcal H 2 O 2 is a cytotoxin. In the present study, we investigated whether streptococcal H 2 O 2 impacts lysosomes, organelles of the intracellular digestive system, in relation to cell death. S. oralis infection induced the death of RAW 264 macrophages in an H 2 O 2 -dependent manner, which was exemplified by the fact that exogenous H 2 O 2 also induced cell death. Infection with either a mutant lacking spxB, which encodes pyruvate oxidase responsible for H 2 O 2 production, or Streptococcus mutans, which does not produce H 2 O 2 , showed less cytotoxicity. Visualization of lysosomes with LysoTracker revealed lysosome deacidification after infection with S. oralis or exposure to H 2 O 2 , which was corroborated by acridine orange staining. Similarly, fluorescent labeling of lysosome-associated membrane protein-1 gradually disappeared during infection with S. oralis or exposure to H 2 O 2 . The deacidification and the following induction of cell death were inhibited by chelating iron in lysosomes. Moreover, fluorescent staining of cathepsin B indicated lysosomal destruction. However, treatment of infected cells with a specific inhibitor of cathepsin B had negligible effects on cell death; instead, it suppressed the detachment of dead cells from the culture plates. These results suggest that streptococcal H 2 O 2 induces cell death with lysosomal destruction and then the released lysosomal cathepsins contribute to the detachment of the dead cells. Streptococcus oralis, a commensal bacterium in the oral cavity, belongs to the group of oral inhabitants of the mitis group of streptococci (1-4). Members of this group, including Streptococcus sanguinis and Streptococcus gordonii, are dominant colonizers of human teeth and are involved in dental plaque formation (1-3). Pathogenic streptococcal species, such as Streptococcus pneumoniae and Streptococcus mitis, are also members of the mitis group (2, 4-6). This group has been implicated as a possible cause of human cardiovascular diseases, including infective endocarditis and atherosclerosis. S. oralis is frequently isolated from cases of infective endocarditis (7-10), and ribosomal DNAs of the mitis group were detected in atheromatous plaque (11). The rate of bacteremia caused by members of the mitis group of streptococci is comparable to that caused by group A or B streptococci (12).The members of the mitis group of streptococci produce hydrogen peroxide (H 2 O 2 ) (2, 13, 14), which is important in bacterial competition in microbial communities, such as oral biofilms (13,14). S. sanguinis and S. gordonii produce H 2 O 2 in quantities sufficient to reduce the growth of many oral bacteria, including the cariogenic bacterium Strepto...

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“…Under normal physiological conditions, NO can adjust the normal physiological function of the human body (23); however, NO is harmful to the body when present at extremely high or low concentrations in vivo (24). NO can induce the production of CAT, strengthening the cell's resistance against H 2 O 2 (25). The classic pathway for the production of NO depends on the activity of NOS, which gradually oxidizes L-arginine into L-guanidine amino acid and produces NO.…”

Section: Discussionmentioning

confidence: 99%

Sevoflurane inhibits the antioxidant capacity of erythrocytes

Yuan³

et al. 2015

Experimental and Therapeutic Medicine

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Abstract. The aim of the present study was to observe the effects of sevoflurane on the antioxidant capacity, endothelial nitric oxide synthase (eNOS) content and lifespan of erythrocytes. A 2% erythrocyte suspension was prepared from whole blood collected from healthy volunteers and then treated with sevoflurane at different concentrations (group A, 0%; group S1, 1%; group S3, 3%; and group S5, 5%), in the presence or absence of 200 µmol/l hydrogen peroxide (H 2 O 2 , or H in group names). In order to evaluate the effects of sevoflurane on the antioxidant capacity and NO metabolism of erythrocytes, the hemolysis rate, catalase (CAT) content and eNOS content were determined, while the labeled phosphatidylserine rate and forward scatter of erythrocytes were detected using flow cyto metry. Group S3 showed the highest hemolysis rate in the absence H 2 O 2 , while treatment with H 2 O 2 increased the hemolysis rate of groups S1 and S3 (P= 0.027). The CAT content in groups treated with sevoflurane was significantly lower compared with that in the control (group A, air group). The CAT content in groups S1+H, S3+H and S5+H remained significantly lower compared with group A+H (P<0.05). The eNOS content of group A was similar to that of group S3, while the content in group S1 was similar to that in group S5. In addition, the eNOS content of groups A and S3 increased, while that of groups S1 and S5 was reduced upon H 2 O 2 treatment (P<0.05). The results indicated that sevoflurane reduced the antioxidative activity of erythrocytes, decreasing the resistant ability to H 2 O 2 damage and increasing the hemolysis rate. The underlying mechanism may be associated with the inhibitory effect on the CAT activity of erythrocytes. Sevoflurane also inhibited the generation of nitric oxide in erythrocytes and reduced the tolerance of erythrocytes against oxidative stress damage due to H 2 O 2 .

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Nitric Oxide Protects Macrophages from Hydrogen Peroxide-Induced Apoptosis by Inducing the Formation of Catalase

Cited by 53 publications

References 63 publications

Apelin Is a Crucial Factor for Hypoxia-Induced Retinal Angiogenesis

Apelin Is a Crucial Factor for Hypoxia-Induced Retinal Angiogenesis

Streptococcus oralis Induces Lysosomal Impairment of Macrophages via Bacterial Hydrogen Peroxide

Sevoflurane inhibits the antioxidant capacity of erythrocytes

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