p38MAPK and ERK promote nitric oxide production in cultured human retinal pigmented epithelial cells induced by high concentration glucose

Yuan, Zhilan; Feng, Weiyan; Jiang, Hong; Zheng, Qi; Shuai, Jie; Ge, Yali

doi:10.1016/j.niox.2008.09.001

Cited by 58 publications

(53 citation statements)

References 52 publications

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“…Neither the concentrations of the inhibitors nor the presence of dimethyl sulfoxide affected the ARPE-19 cell viability as determined by the WST-8 assay (data not shown) and by earlier reports. 23,24 The assays were performed in triplicate, and three independent experiments were carried out.…”

Section: Cytokine and Chemokine Analysis And Signaling Pathways In Armentioning

confidence: 99%

Toxic effects of extracellular histones and their neutralization by vitreous in retinal detachment

Kawano

Ito

Yamada³

et al. 2014

Laboratory Investigation

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Histones are DNA-binding proteins and are involved in chromatin remodeling and regulation of gene expression. Histones can be released after tissue injuries, and the extracellular histones cause cellular damage and organ dysfunction. Regardless of their clinical significance, the role and relevance of histones in ocular diseases are unknown. We studied the role of histones in eyes with retinal detachment (RD). Vitreous samples were collected during vitrectomy, and the concentration of histone H3 was measured by enzyme-linked immunosorbent assay. The location of the histones and related molecules was examined in a rat RD model. The release of histones and their effects on rat retinal progenitor cells R28 and ARPE-19 were evaluated in vitro. In addition, the protective role of the vitreous body against histones was tested. The intravitreal concentration of histones was higher in eyes with RD (mean, 30.9±9.8 ng/ml) than in control eyes (below the limit of detection, Po0.05). In the rat RD model, histone H3 was observed on the outer side of the detached retina and was associated with photoreceptor death. Histone H3 was released from cultured R28 by oxidative stress. Histones at a concentration 10 mg/ml induced the production of interleukin-8 in ARPE-19 cells (2.5-fold increase, Po0.05) that was mediated through the ERK1/2-and p38 MAPK-dependent pathways and Toll-like receptor 4. Histones were toxic to cells at concentrations of Z20 mg/ml. Vitreous body or hyaluronan decreased toxicity of histones by inhibiting diffusion of histones. These results indicate that histones are released from retinas with RD and may modulate the subretinal microenvironment by functioning as damage-associated molecular pattern molecules, thereby inducing proinflammatory cytokines or cell toxicity. In addition, the important role of the vitreous body and hyaluronan in protecting the retina from these toxic effects is suggested.

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Section: Cytokine and Chemokine Analysis And Signaling Pathways In Armentioning

confidence: 99%

Toxic effects of extracellular histones and their neutralization by vitreous in retinal detachment

Kawano

Ito

Yamada³

et al. 2014

Laboratory Investigation

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“…Apesar de seu papel endógeno essencial, diversos estudos já demonstram que o excesso de NO pode estar envolvido na gênese e desenvolvimento de inúmeras patologias (Robinson et al, 2001;Virág et al, 2003;Ippoushi, 2009;Yuan et al, 2009), por exemplo, da retinopatia diabética (Yuan et al, 2009) e desordens neurodegenerativas (Saha et al, 2006) como a esclerose múltipla (Horssen et al, 2008). Dessa forma, compostos que sejam capazes de sequestrar o NO podem ser alternativas para a prevenção e terapia dessas desordens.…”

Section: Resultsunclassified

“…O radical óxido nítrico é uma molécula endógena envolvida em inúmeros processos fisiológicos que variam desde a neurotransmissão (Katzung, 2006;Yuan et al, 2009) até modulação do estado inflamatório, agindo na agregação plaquetária, vasodilatação (Saha et al, 2006), quimiotaxia e possuindo ação bactericida (Katzung, 2006). Em altas concentrações o NO pode reagir com o ânion superóxido produzindo o potencialmente danoso peroxinitrito (Peluffo & Radi, 2007), aumentando o estado de estresse oxidativo, induzindo peroxidação lipídica, desestabilidade nas membranas, oxidação e nitração de proteínas e danos ao DNA (Robinson et al, 2001, Virág et al, 2003Ippoushi, 2009;Yuan et al, 2009).…”

Section: Introductionunclassified

“…Em altas concentrações o NO pode reagir com o ânion superóxido produzindo o potencialmente danoso peroxinitrito (Peluffo & Radi, 2007), aumentando o estado de estresse oxidativo, induzindo peroxidação lipídica, desestabilidade nas membranas, oxidação e nitração de proteínas e danos ao DNA (Robinson et al, 2001, Virág et al, 2003Ippoushi, 2009;Yuan et al, 2009). Devido a isto, tem sido aceito que a formação de peroxinitrito e sua subsequente reação com produtos endógenos podem estar envolvidos na patogênese de doenças, incluindo algumas desordens neurodegenerativas (Saha et al, 2006), complicações do estado diabético (a exemplo da retinopatia) (Yuan et al, 2009) cancerígenos (Radi & Peluffo, 2001). Assim, substâncias que sequestrem o radical óxido nítrico podem desempenhar um importante papel citoprotetor, agindo nos processos de toxidade induzida por espécies reativas de nitrogênio (RNS), modulando os processos inflamatórios, diminuindo o estado de estresses oxidativo e podendo apresentarse como alternativa terapêutica para algumas dessas desordens (Saha et al, 2006).…”

Section: Introductionunclassified

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Avaliação do sequestro do óxido nítrico (NO) pelo extrato metanólico da alga Bryothamnion triquetrum (Gmelin) Howe

Maia¹,

Moura²,

Bispo³

et al. 2010

Rev. bras. farmacogn.

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RESUMO: O excesso de óxido nítrico (NO) produzido por indução da enzima óxido nítrico sintase (iNOS) participa do desenvolvimento de inúmeras desordens que conduzem à perda da homeostasia. O estresse oxidativo gerado pelo aumento da produção endógena de NO pode levar a efeitos de toxidade induzida, tais como peroxidação lipídica, nitração de proteínas e danos ao DNA. Compostos que sejam capazes de sequestrar o radical NO podem diminuir a toxicidade das espécies reativas de nitrogênio (RNS), atuando na modulação de processos inflamatórios. Trabalhos realizados com alga da espécie Bryothamnion triquetrum (Gmelin) Howe, demonstraram que a mesma apresenta ação antioxidante, tendo sido eficiente no sequestro do radical DPPH, além de inibição da peroxidação lipídica, com uma atividade comparável ao ácido ascórbico e ao α-tocoferol. Este estudo objetivou avaliar a capacidade de sequestro do radical NO in vitro pelo extrato metanólico da Bryothamnion triquetrum. Os resultados obtidos revelaram a presença de polifenóis sendo que todas as concentrações testadas (1,0; 2,5; 7,5; 10,0 mg/mL) foram capazes de inibir a formação de nitrito a partir de uma solução de nitroprussiato de sódio 5 mM sendo a concentração de 7,5 mg/mL a que apresentou maior percentual de inibição com 46,6%.Unitermos: óxido nítrico, Bryothamnion triquetrum, estresse oxidativo.ABSTRACT: "Evaluation of nitric oxide (NO) scavenging for the metanol extract of the alga Bryothamnion triquetrum (Gmelin) Howe". The excess of nitric oxide (NO) produced by induction of nitric oxide sintase enzyme (iNOS) participates in the development of countless disorders that lead to the loss of homeostasis. The oxidative stress generated by the increase of endogenous production of NO can lead to some effects of induced toxicity, such as fatty per oxidation, nitration of proteins and DNA damages. Compounds that scavenge the NO radical can reduce the toxicity of reactive nitrogen species (RNS), and act in the modulation of inflammatory processes. Works accomplished with the alga species Bryothamnion triquetrum (Gmelin) Howe demonstrated that it presents an antioxidant action, and it is efficient in the scavenging of DPPH radical and in the inhibition of fatty per oxidation, with activity comparable to the ascorbic acid and α-tocoferol. This study aimed to evaluate the capacity of NO radical scavenging in vitro for the methanol extract of the alga Bryothamnion triquetrum. The results revealed that the presence of poliphenol in all tested concentrations (1,0; 2,5; 7,5; 10,0 mg/mL) was capable to inhibit the nitrite formation, starting from a solution of sodium nitroprussiate 5 mM whose concentration of 7,5 mg/mL presented the largest inhibition percentage of 46,6%.

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“…The viability of normal MCF-7 cells and CDK5RAP1-deficient MCF-7 cells was determined by a colorimetric MTT assay according to the method described previously (18). Absorbance at 550 nm was determined by an MTP-800 microplate reader (Corona Electric, Tokyo, Japan).…”

Section: -(45-dimethylthiazol-2-yl)-25-diphenyltetrazolium Bromidementioning

confidence: 99%

CDK5RAP1 deficiency induces cell cycle arrest and apoptosis in human breast cancer cell line by the ROS/JNK signaling pathway

Wang

et al. 2015

Oncology Reports

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Abstract. Cyclin-dependent kinase 5 regulatory subunit associated protein 1 (CDK5RAP1) is an enzyme which post-synthetically converts the RNA modification N6-isopentenyladenosine (i 6 A) into 2-methylthio-N6-isopentenyladenosine (ms 2 i 6 A). However, the interaction between CDK5RAP1 deficiency and cell apoptosis has not been studied. Breast cancer has long been a leading cause of mortality in the world. Therefore, in the present study, CDK5RAP1 deficiency in a human breast cancer cell line was investigated. CDK5RAP1 small interfering RNA (siRNA) and negative control siRNA were transfected into MCF-7 cells, and the cells were further incubated for 48 h. CDK5RAP1 deficiency suppressed tumor growth in MCF-7 cells and arrested the cells at G2/M phase. CDK5RAP1 deficiency also induced cell apoptosis and reactive oxygen species (ROS) generation. Furthermore, western blot analysis showed that the expression of phospho-c-Jun N-terminal kinase (p-JNK), p53, caspase-9 and caspase-3 were upregulated in CDK5RAP1-deficient MCF-7 cells. Pretreatment with N-acetyl-cysteine (NAC), the inhibitor of ROS, or with SP600125, the inhibitor of JNK, prevented the apoptosis and the high expression of p-JNK, p53, caspase-9 and caspase-3 in CDK5RAP1-deficient MCF-7 cells. Taken together, these data indicated that CDK5RAP1 deficiency induced cell cycle arrest and apoptosis in human breast cancer MCF-7 cells by the ROS/JNK signaling pathway. Our findings indicated a novel therapeutic strategy for cancer. IntroductionCyclin-dependent kinase 5 regulatory subunit associated protein 1 (CDK5RAP1) is a radical S-adenosyl methionine (SAM) enzyme (1) with homology to the bacterial MiaB protein (2), which post-synthetically converts the RNA modification N6-isopentenyladenosine (i 6 A) into 2-methylthio-N6-isopentenyladenosine (ms 2 i 6 A) at A37 (3), as shown in Fig. 1A. It was discovered to inhibit the active CDK5 kinase and function in codon suppression (4) and stabilization of the codon/anticodon interaction (5). CDK5 aberrant regulation can lead to a number of diseases (6). The biochemical link established by CDK5RAP1 between the enzymatic modification of transfer RNA (tRNA) tanticodon loops and CDK5 kinase activity is highly unusual, particularly since the modified base ms 2 i 6 A is known to exist in tRNA of prokaryotic origin (7), particularly in mitochondrial tRNA of mammals (8).Breast cancer has long been a leading cause of mortality in women worldwide (9). Due to the limited efficacy of traditional therapy, it is necessary to exploit a new treatment strategy for breast cancer. Mitochondria-initiated responses are thought to be the major pathway for apoptosis, and, therefore, targeting the mitochondria is a novel strategy for cancer therapy (10). Hence, in the present study, we sought to determine if the mistranslation of ms 2 i 6 A in mitochondrial tRNA caused by CDK5RAP1 deficiency affects the human breast cancer cell line, MCF-7 cells.Cell cycle arrest is an important cause of growth inhibition. Many anticancer agents reduce malignant g...

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p38MAPK and ERK promote nitric oxide production in cultured human retinal pigmented epithelial cells induced by high concentration glucose

Cited by 58 publications

References 52 publications

Toxic effects of extracellular histones and their neutralization by vitreous in retinal detachment

Toxic effects of extracellular histones and their neutralization by vitreous in retinal detachment

Avaliação do sequestro do óxido nítrico (NO) pelo extrato metanólico da alga Bryothamnion triquetrum (Gmelin) Howe

CDK5RAP1 deficiency induces cell cycle arrest and apoptosis in human breast cancer cell line by the ROS/JNK signaling pathway

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