Roles of ROS and PKC-βII in ionizing radiation-induced eNOS activation in human vascular endothelial cells

Sakata, Kei; Kondo, Takashi; Mizuno, Natsumi; Shoji, Mitsuru; Yasui, Hirofumi; Yamamori, Tohru; Inanami, Osamu; Yokoo, Hiroki; Yoshimura, Naoki; Hattori, Yoshiyuki

doi:10.1016/j.vph.2015.03.016

Cited by 28 publications

(21 citation statements)

References 32 publications

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“…Blotting procedure, chemiluminescent detection, and densitometric analysis were performed as described in our previous reports (Sakata et al . ; Wang et al . ; Sakai et al .…”

Section: Methodsmentioning

confidence: 99%

Role of G protein‐coupled receptor kinase 2 in oxidative and nitrosative stress‐related neurohistopathological changes in a mouse model of sepsis‐associated encephalopathy

Kawakami

Hattori

Ohashi

et al. 2018

Journal of Neurochemistry

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Sepsis-associated encephalopathy (SAE), characterized as diffuse brain dysfunction and neurological manifestations secondary to sepsis, is a common complication in critically ill patients and can give rise to poor outcome, but understanding the molecular basis of this disorder remains a major challenge. Given the emerging role of G protein-coupled receptor 2 (GRK2), first identified as a G protein-coupled receptor (GPCR) regulator, in the regulation of non-G protein-coupled receptor-related molecules contributing to diverse cellular functions and pathology, including inflammation, we tested the hypothesis that GRK2 may be linked to the neuropathogenesis of SAE. When mouse MG6 microglial cells were challenged with lipopolysaccharide (LPS), GRK2 cytosolic expression was highly up-regulated. The ablation of GRK2 by small interfering RNAs (siRNAs) prevented an increase in intracellular reactive oxygen species generation in LPS-stimulated MG6 cells. Furthermore, the LPS-induced up-regulation of inducible nitric-oxide synthase expression and increase in nitric oxide production were negated by GRK2 inhibitor or siRNAs. However, GRK2 inhibition was without effect on overproduction of tumor necrosis factor-α, interleukin (IL)-6, and IL-1β in LPS-stimulated MG cells. In mice with cecal ligation and puncture-induced sepsis, treatment with GRK2 inhibitor reduced high levels of oxidative and nitrosative stress in the mice brains, where GRK2 expression was up-regulated, alleviated neurohistological damage observed in cerebral cortex sections, and conferred a significant survival advantage to CLP mice. Altogether, these results uncover the novel role for GRK2 in regulating cellular oxidative and nitrosative stress during inflammation and suggest that GRK2 may have a potential as an intriguing therapeutic target to prevent or treat SAE.

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“…Blotting procedure, chemiluminescent detection, and densitometric analysis were performed as described in our previous reports (Sakata et al . ; Wang et al . ; Sakai et al .…”

Section: Methodsmentioning

confidence: 99%

Role of G protein‐coupled receptor kinase 2 in oxidative and nitrosative stress‐related neurohistopathological changes in a mouse model of sepsis‐associated encephalopathy

Kawakami

Hattori

Ohashi

et al. 2018

Journal of Neurochemistry

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“…Cell viability assay. Cell viability was assessed using the colorimetric MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) tetrazolium reduction assay (27). Cells were seeded in 96-well plates at 20,000 per well and cultivated for 24-48 h before the onset of treatment with resveratrol, SIRT1720, or their vehicle DMSO.…”

Section: Methodsmentioning

confidence: 99%

Different effect of resveratrol to induction of apoptosis depending on the type of human cancer cells

Takashina

Inoue

Tomihara

et al. 2017

International Journal of Oncology

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The effect of resveratrol on various human cancer cells was investigated with special focus on apoptotic cell death, in an attempt to further characterize its mechanism of action. There were great differences in the anti-viability effect of resveratrol between different types of human cancer cells. While the inhibition of cell viability by resveratrol was marked in U937 and MOLT-4 leukemia cells, resveratrol moderately inhibited cell viability in MCF-7 breast, HepG2 liver, and A549 lung cancer cells, and the effect was slight on cell viability in Caco-2, HCT116, and SW480 colon cancer cells. Following resveratrol treatment, U937 and MOLT-4 markedly increased the population of late apoptotic cells but MCF-7 and HepG2 underwent apoptosis with an increased population of early apoptosis, and resveratrol-induced DNA fragmentation was observed only in leukemic cells. Activation of sirtuin 1 and adenosine-monophosphate-activated protein kinase was not responsible for resveratrol-induced cancer cell death. Instead, resveratrol significantly reduced Akt activation with the downregulation of H-Ras, resulting in facilitation of Bax translocation to mitochondria in leukemic cells. This study suggests that resveratrol can induce apoptotic cell death in human leukemic cells to a greater extent than in human solid tumor cells via reducing Akt activation due to Ras downregulation.

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“…Certain previous experiments have demonstrated that phosphorylation of eNOS at Thr495 is PKC-dependent (21)(22)(23)(24). In order to elucidate a potential upstream signaling molecule of ERK1/2, PKC, another member of the protein kinase familiar, was investigated with phospho-specific anti-PKC antibodies (data not shown); however no stimulus-related changes in the association of classical PKC and eNOS-Thr495 were observed.…”

Section: Discussionmentioning

confidence: 99%

Modulation of low shear stress-induced eNOS multi-site phosphorylation and nitric oxide production via protein kinase and ERK1/2 signaling

Kong

et al. 2016

Molecular Medicine Reports

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Abstract.Physiological shear stress has been demonstrated to serve an atheroprotective function by stimulating endothelial nitric oxide synthase (eNOS) multi-site phosphorylation. Low shear stress (LSS) serves an atheroprone role by increasing endothelial cell apoptosis and inflammation. The present study assessed whether LSS inhibited nitric oxide (NO) production in human umbilical vein endothelial cells by modulating eNOS phosphorylation and potential signaling pathways. A parallel flow chamber imposed with 2 dyn/cm 2 shear stress on endothelial cells was used. Western blotting and 4,5-diaminofluorescein diacetate were used to analyze the protein expression levels and NO production. LSS activated eNOS-Ser1177 and eNOS-Thr495, but inhibited eNOS-Ser633. NO production was decreased after a transient increase at 5 min. LSS-stimulated phosphorylation of eNOS-Ser1177 and -Thr495 were suppressed by the Akt inhibitor, perifosine, and extracellular signal regulated kinases1/2 (ERK1/2) inhibitor, PD98059, respectively. Additionally, the phosphorylation of eNOS-Ser633 inhibited by LSS was restored by the protein kinase A activator, 8-Bromo-cAMP. PD98059 completely inhibited the LSS-induced downregulation of NO production. NO downregulation in response to LSS was intensified by perifosine and was partly inhibited by 8-Bromo-cAMP. These results indicated that LSS-induced activation of ERK1/2/eNOS-Thr495 serves a major role in inhibiting endothelial NO synthase, which may explain the proinflammatory and proatherosclerotic properties of LSS.

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Roles of ROS and PKC-βII in ionizing radiation-induced eNOS activation in human vascular endothelial cells

Cited by 28 publications

References 32 publications

Role of G protein‐coupled receptor kinase 2 in oxidative and nitrosative stress‐related neurohistopathological changes in a mouse model of sepsis‐associated encephalopathy

Role of G protein‐coupled receptor kinase 2 in oxidative and nitrosative stress‐related neurohistopathological changes in a mouse model of sepsis‐associated encephalopathy

Different effect of resveratrol to induction of apoptosis depending on the type of human cancer cells

Modulation of low shear stress-induced eNOS multi-site phosphorylation and nitric oxide production via protein kinase and ERK1/2 signaling

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