Nucleolin Is a Receptor for Maleylated-Bovine Serum Albumin on Macrophages

Miki, Yuichi; Koyama, Keisuke; Kurusu, Haruna; Hirano, Kazuya; Beppu, Masatoshi; Fujiwara, Yasuyuki

doi:10.1248/bpb.b14-00624

Cited by 6 publications

(10 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We recently reported that nucleolin is a phagocytic receptor that initiates the removal of a variety of discarded elements. [10][11][12][13] These previous observations and the present study support our hypothesis that cell surface-expressed nucleolin on phagocytes has a general scavenger-like ability.…”

Section: Phagocytosis Of Acldl By Macrophagessupporting

confidence: 92%

“…The same observations were also made regarding the binding of nucleolin with other anionic molecules, including glycosylated protein 12) and maleylated protein. 13) These findings suggest that not only an ionic bond but also superstructural modifications are required for the binding of AcLDL to nucleolin. At present, however, no definitive explanation has been given for this binding mechanism.…”

Section: Dnamentioning

confidence: 93%

“…9) RNA, 9) sialyl polylactosamine carbohydrate chain 10) and maleylated 13) or glycosylated proteins. 12) Taken together, these findings suggest that the polyanionic nature of AcLDL might play a major role in its binding to nucleolin.…”

Section: Dnamentioning

confidence: 99%

“…8,9) We previously identified nucleolin as a scavenger receptor for apoptotic cells 10) and modified proteins such as fibril amyloid-β, 11) advanced glycosylation end products, 12) and maleylated-proteins. 13) In addition, nucleolin is a scavenger receptor for microbes and their substituents, including lipopolysaccharide, 14) enterohemorrhagic Escherichia coli (E. coli) O157 : H7, 15) and human parainfluenza virus type 3.…”

mentioning

confidence: 99%

See 3 more Smart Citations

Nucleolin Acts as a Scavenger Receptor for Acetylated Low-Density Lipoprotein on Macrophages

Miki

Tachibana

Ohminato

et al. 2015

Biological & Pharmaceutical Bulletin

Self Cite

View full text Add to dashboard Cite

Although macrophage phagocytoses modified low-density lipoprotein (LDL), excessive accumulation of modified LDL induces macrophage foam cell formation, which is a feature of atherosclerotic plaque. Thus, the identification of scavenger receptor for modified LDL will provide better understanding of an atherosclerotic event. We recently showed that nucleolin expressed on macrophages acts as a scavenger receptor for various endogenous discarded products. Here, we investigated whether or not nucleolin is involved in the uptake of acetylated LDL (AcLDL). In contrast to normal LDL, AcLDL directly bound to immobilized nucleolin. AcLDL exhibited a higher affinity for macrophages than normal LDL. This binding of AcLDL was inhibited by anti-nucleolin antibody and antineoplastic guanine-rich oligonucleotide (AGRO), a nucleolinspecific oligonucleotide aptamer. In addition, AcLDL exhibited a higher affinity for HEK cells transfected with nucleolin than those without. Further, intracellular accumulation of AcLDL was also inhibited by antinucleolin antibody. The results of this study suggest that nucleolin expressed on macrophages is a receptor for AcLDL.Key words nucleolin; macrophage; acetylated low-density lipoprotein (AcLDL); scavenger receptor Low-density lipoprotein (LDL) elevates cholesterol deposits in macrophage foam cells, which are involved in the development of atherosclerotic lesions.1) As the uptake of normal LDL via its receptor is controlled by feedback regulation, excess levels of LDL-derived cholesterol in macrophages might be attributed to modifications of LDL such as oxidation, acetylation, and aggregation.2) Scavenger receptors (SRs) and other unknown receptors account for up to 95% of the uptake of modified LDL.

show abstract

Section: Phagocytosis Of Acldl By Macrophagessupporting

confidence: 92%

Section: Dnamentioning

confidence: 93%

Section: Dnamentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Nucleolin Acts as a Scavenger Receptor for Acetylated Low-Density Lipoprotein on Macrophages

Miki

Tachibana

Ohminato

et al. 2015

Biological & Pharmaceutical Bulletin

Self Cite

View full text Add to dashboard Cite

show abstract

“…BSA, AGE-2, and AGE-3 were fluorescently labelled as described previously with some modification 15 , 16 . Briefly, each protein was incubated with 20 times the amount of Alexa Fluor 488 C5 maleimide (Thermo Fisher Scientific) at room temperature for 2 h in phosphate buffered saline (PBS) and then dialysed with PBS at 4 °C for 2 days.…”

Section: Methodsmentioning

confidence: 99%

Effects of scavenger receptors-1 class A stimulation on macrophage morphology and highly modified advanced glycation end product-protein phagocytosis

Hamasaki

Kobori

Yamazaki

et al. 2018

Sci Rep

View full text Add to dashboard Cite

Advanced glycation end-products (AGEs), which comprise non-enzymatically glycosylated proteins, lipids, and nucleic acid amino groups, play an important role in several diseases and aging processes including angiopathy, renal failure, diabetic complications, and neurodegenerative diseases. Among AGE-associated phenotypes, toxic AGEs, glyceraldehyde-derived AGE-2, and glycolaldehyde-derived AGE-3 are involved in the pathogenesis of diabetic complications. In addition, macrophages are reported to remove extracellular AGEs from tissues via scavenger receptors, leading to the progression of atherosclerosis. In the present study, we found that AGE-2 and AGE-3 enhanced their own endocytic uptake by RAW264.7 mouse macrophage-like cells in a concentration-dependent manner. Furthermore, we demonstrated, for the first time, the morphology of phagocytic macrophages and the endocytosis of AGE particles. The toxic AGEs induced the expression of a scavenger receptor, CD204/scavenger receptors-1 class A (SR-A). Notably, an antibody against CD204 significantly prevented toxic AGE uptake. Moreover, an SR-A antagonistic ligand, fucoidan, also attenuated the AGE-2- and AGE-3-evoked uptake in a concentration-dependent manner. These results indicated that SR-A stimulation, at least in part, plays a role in AGE uptake.

show abstract

Nucleolin Mediates LPS-induced Expression of Inflammatory Mediators and Activation of Signaling Pathways

Wang

Huang

et al. 2020

CURR MED SCI

View full text Add to dashboard Cite

In this study, we investigated the effects of nucleolin on lipopolysaccharide (LPS)induced activation of MAPK and NF-KappaB (NF-κB) signaling pathways and secretion of TNF-α, IL-1β and HMGB1 in THP-1 monocytes. Immunofluorescence assay and Western blotting were used to identify the nucleolin expression in cell membrane, cytoplasm and nucleus of THP-1 monocytes. Inactivation of nucleolin was induced by neutralizing antibody against nucleolin. THP-1 monocytes were pretreated with anti-nucleolin antibody for 1 h prior to LPS challenge. The irrelevant IgG group was used as control. Secretion of inflammatory mediators (TNF-α, IL-1β and HMGB1) and activation of MAPK and NF-κB/I-κB signaling pathways were examined to assess the effects of nucleolin on LPS-mediated inflammatory response. Nucleolin existed in cell membrane, cytoplasm and nucleus of THP-1 monocytes. Pretreatment of anti-nucleolin antibody significantly inhibited the LPS-induced secretion of TNF-α, IL-1β and HMGB1. P38, JNK, ERK and NF-κB subunit p65 inhibitors could significantly inhibit the secretion of IL-1β, TNF-α and HMGB1 induced by LPS. Moreover, the phosphorylation of p38, JNK, ERK and p65 (or nuclear translocation of p65) was significantly increased after LPS challenge. In contrast, pretreatment of anti-nucleolin antibody could significantly inhibit the LPS-induced phosphorylation of p38, JNK, ERK and p65 (or nuclear translocation of p65). However, the irrelevant IgG, as a negative control, had no effect on LPS-induced secretion of TNF-α and IL-1β and phosphorylation of p38, JNK, ERK and p65 (or nuclear translocation of p65). We demonstrated that nucleolin mediated the LPS-induced activation of MAPK and NF-κB signaling pathways, and regulated the secretion of inflammatory mediators (TNF-α, IL-1β and HMGB1).

show abstract

Nucleolin Is a Receptor for Maleylated-Bovine Serum Albumin on Macrophages

Cited by 6 publications

References 28 publications

Nucleolin Acts as a Scavenger Receptor for Acetylated Low-Density Lipoprotein on Macrophages

Nucleolin Acts as a Scavenger Receptor for Acetylated Low-Density Lipoprotein on Macrophages

Effects of scavenger receptors-1 class A stimulation on macrophage morphology and highly modified advanced glycation end product-protein phagocytosis

Nucleolin Mediates LPS-induced Expression of Inflammatory Mediators and Activation of Signaling Pathways

Contact Info

Product

Resources

About