Identification of plasma APE1/Ref-1 in lipopolysaccharide-induced endotoxemic rats: Implication of serological biomarker for an endotoxemia

Park, Myoung Soo; Lee, Yu Ran; Choi, Sunga; Joo, Hee Kyoung; Cho, Eun Jung; Kim, Cuk-Seong; Park, Jin Bong; Jo, Eun-Kyeong; Jeon, Byeong Hwa

doi:10.1016/j.bbrc.2013.05.030

Cited by 22 publications

(40 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The finding by Park et al, showing the presence of plasma APE1 upon lipopolysaccharide (LPS)-induced endotoxemia in rats, provided the evidence of APE1 secretion upon a typical inflammatory response in an in vivo system [7]. To determine the cellular source of this plasma APE1, we stimulated peripheral blood mononuclear cells, (PBMCs) isolated from blood samples of normal donors, with LPS.…”

Section: Resultsmentioning

confidence: 99%

“…While recent evidences indicate that APE1 can be secreted into the plasma [6, 7], the physiological or pathological role of extracellular APE1 has not been documented yet. In this study, for the first time, we show that the oxidative DNA damage repair protein APE1 can be actively released from monocytes upon inflammatory challenges.…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, a recent report demonstrated the secretion of APE1 into the extracellular medium in cultured HEK293 and tumor cells [6]. Concurrently, another report identified the presence of plasma APE1 in lipopolysaccharide (LPS)-induced endotoxemic rats [7]. While these reports support the idea that APE1 can be secreted from cells, the biological relevance of APE1 secretion into the plasma remains elusive.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

The extracellular role of DNA damage repair protein APE1 in regulation of IL-6 expression

Nath

Roychoudhury

Kling

et al. 2017

Cellular Signalling

View full text Add to dashboard Cite

The human apurinic/apyrimidinic endonuclease 1 (APE1) is a pleiotropic nuclear protein with roles in DNA base excision repair pathway as well as in regulation of transcription. Recently, the presence of extracellular plasma APE1 was reported in endotoxemic rats. However, the biological significance and the extracellular function of APE1 remain unclear. In this study, we found that monocytes secrete APE1 upon inflammatory challenges. Challenging the monocytic cells with extracellular APE1 resulted in the increased expression and secretion of the pro-inflammatory cytokine IL-6. Additionally, the extracellular APE1 treatment activated the transcription factor NF-κB, followed by its increased occupancy at the IL-6 promoter, resulting in the induction of IL-6 expression. APE1-induced IL-6 further served to elicit autocrine and paracrine cellular responses. Moreover, the extracellular IL-6 promoted the secretion of APE1, thus indicating a functional feedforward loop in this pathway. Furthermore, we show that APE1 is secreted through extracellular vesicles formation via endosomal sorting complex required for transport (ESCRT)-dependent pathway. Together, our study demonstrates a novel role of extracellular APE1 in IL-6-dependent cellular responses.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The extracellular role of DNA damage repair protein APE1 in regulation of IL-6 expression

Nath

Roychoudhury

Kling

et al. 2017

Cellular Signalling

View full text Add to dashboard Cite

show abstract

“…Although many reports have showed that APE1/Ref-1 is localized to the nucleus and the underlying mechanism for serum APE1/Ref-1 existence is completely elucidated, it was recently reported that APE1/Ref-1 was secreted into the bloodstream in response to lipopolysaccharides. 13) 14) In lung and bladder cancer, elevation of serum APE1/Ref-1 has been identified. 15) 16) Considering that CAD is associated with chronic inflammation, ROS, and IR injury, the elevation of APE1/Ref-1 in the sera of patients with CAD may be natural and expected.…”

Section: Discussionmentioning

confidence: 99%

Elevation of the Serum Apurinic/Apyrimidinic Endonuclease 1/Redox Factor-1 in Coronary Artery Disease

et al. 2015

Self Cite

View full text Add to dashboard Cite

Background and ObjectivesApurinic/apyrimidinic endonuclease 1/redox effector factor-1 (APE1/Ref-1) is a multifunctional protein involved in the DNA base excision repair pathway, inflammation, angiogenesis, and survival pathways. We investigated serum APE1/Ref-1 in patients with coronary artery disease (CAD).Subjects and MethodsSerum APE1/Ref-1 was measured with a sandwich enzyme-linked immunosorbent assay from 360 patients who received coronary angiograms. They were divided into two groups; a control (n=57) and a CAD group (n=303), the latter included angina (n=128) and myocardial infarction (MI, n=175).ResultsThe levels of APE1/Ref-1 were higher in the CAD than the control (0.63±0.07 vs. 0.12±0.07 ng/100 µL, respectively; p<0.01). They were also higher in MI than angina (0.81±0.10 vs. 0.38±0.11 ng/100 µL, respectively; p<0.01) and different according to the thrombolysis in myocardial infarction (TIMI) flow (0.88±0.09 for TIMI flow 0, 1, 2 vs. 0.45±0.13 ng/100 µL for TIMI flow 3, p<0.01) in acute coronary syndrome. In correlation analysis, the levels of APE1/Ref-1 were positively correlated with Troponin I (r=0.222; p<0.0001) and N-terminal pro-B type natriuretic peptide (NT-proBNP, r=0.217; p<0.0001) but not high sensitivity to C-reactive protein. Also, they revealed a negative correlation with ejection fraction (EF, r=-0.221; p=0.002). However, there were no significant differences among the three groups, were divided by their levels of APE1/Ref-1, for major adverse cardiovascular events (death, recurrent MI, stroke, revascularization) (8.2 vs. 14.0 vs. 12.5%, p=ns).ConclusionThe levels of serum APE1/Ref-1 are elevated in CAD, and are higher in MI than in angina. They are correlated with Troponin I, NT-proBNP, and EF.

show abstract

“…All animal experiments adhered to the Chungnam National University policies regarding the care and use of animals. As described previously [54, 55], KA was injected using a 50-μl Hamilton microsyringe fitted with a 26-gauge needle (0.1 μg/5 μl in PBS, i.c.v), and LPS was injected intraperitoneally (10 mg/kg, i.p.). The same volume of phosphate-buffered saline was injected i.c.v or i.p.…”

Section: Methodsmentioning

confidence: 99%

The anti-inflammatory role of extranuclear apurinic/apyrimidinic endonuclease 1/redox effector factor-1 in reactive astrocytes

et al. 2016

Self Cite

View full text Add to dashboard Cite

Apurinic/apyrimidinic endonuclease 1 (APE1), a ubiquitous multipurpose protein, is also known as redox effector factor-1 (Ref-1). It is involved in DNA repair and redox signaling and, in turn, oxidative stress-induced neurodegeneration. Although previous studies have demonstrated that APE1/Ref-1 functions as a negative regulator of inflammatory response via several mechanisms in neuronal cells, little is known about the roles of APE1/Ref-1 in glial cells. In this study, we found that cytoplasmic APE1/Ref-1 expression was upregulated in reactive astrocytes of the kainic acid- or lipopolysaccharide (LPS)-injected hippocampus. Analysis of the inflammatory response induced by extranuclear APE1/Ref-1 (ΔNLS-Ref-1) in cultured primary astrocytes revealed that it markedly suppressed inducible nitric oxide synthase (iNOS) expression and tumor necrosis factor-α (TNF-α) secretion induced by LPS to a similar extent as did wild type APE1/Ref-1 (WT-Ref-1), supporting the concept an anti-inflammatory role of extranuclear APE1/Ref-1 in astrocytes. Additionally, overexpression of WT- and ΔNLS-Ref-1 suppressed the transcriptional activity of nuclear factor-κB (NF-κB), although it effectively enhanced activator protein 1 (AP-1) activity. The blunting effect of APE1/Ref-1 on LPS-induced NF-κB activation was not mediated by IκB kinase (IKK) activity. Instead, APE1/Ref-1 inhibited p300-mediated acetylation of p65 by suppressing intracellular reactive oxygen species (ROS) levels following LPS treatment. Taken together, our results showed that altered expression and/or subcellular distribution of APE1/Ref-1 in activated astrocytes regulated the neuroinflammatory response to excitotoxin and endotoxin insults used in model of neurodegenerative brain diseases.

show abstract

Identification of plasma APE1/Ref-1 in lipopolysaccharide-induced endotoxemic rats: Implication of serological biomarker for an endotoxemia

Cited by 22 publications

References 27 publications

The extracellular role of DNA damage repair protein APE1 in regulation of IL-6 expression

The extracellular role of DNA damage repair protein APE1 in regulation of IL-6 expression

Elevation of the Serum Apurinic/Apyrimidinic Endonuclease 1/Redox Factor-1 in Coronary Artery Disease

The anti-inflammatory role of extranuclear apurinic/apyrimidinic endonuclease 1/redox effector factor-1 in reactive astrocytes

Contact Info

Product

Resources

About