Prothrombin is a binding partner of the human receptor of advanced glycation end products

Degani, Genny; Altomare, Alessandra; Digiovanni, Stefania; Arosio, Beatrice; Fritz, Günter; Raucci, Angela; Aldini, Giancarlo; Popolo, Laura

doi:10.1074/jbc.ra120.013692

Cited by 6 publications

(8 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It has been shown that ligand binding mainly occurs in the V-type domain ( 2 ). The V-shaped structure of its extracellular ligand binding part can bind to the Gla domain of prothrombin (F2) under normal physiological conditions ( 3 , 4 ). Under normal physiological conditions, the expression level of RAGE is low; however, due to the accumulation of RAGE ligands, the expression of RAGE is upregulated under inflammatory conditions ( 5 ).…”

Section: Introductionmentioning

confidence: 99%

Inflammation and coagulation abnormalities via the activation of the HMGB1‑RAGE/NF‑κB and F2/Rho pathways in lung injury induced by acute hypoxia

Zhang¹,

Yan²,

Ge³

et al. 2023

Int J Mol Med

View full text Add to dashboard Cite

High-altitude acute hypoxia is commonly associated with respiratory cardiovascular diseases. The inability to adapt to acute hypoxia may lead to cardiovascular dysfunction, lung injury and even death. Therefore, understanding the molecular basis of the adaptation to high-altitude acute hypoxia may reveal novel therapeutic approaches with which to counteract the detrimental consequences of hypoxia. In the present study, a high-altitude environment was simulated in a rat model in order to investigate the role of the high mobility group protein-1 (HMGB1)/receptor for advanced glycation end products (RAGE)/NF-κB and F2/Rho signaling pathways in lung injury induced by acute hypoxia. It was found that acute hypoxia caused inflammation through the HMGB1/RAGE/NF-κB pathway and coagulation dysfunction through the F2/Rho pathway, both of which may be key processes in acute hypoxia-induced lung injury. The present study provides new insight into the molecular basis of lung injury induced by acute hypoxia. The simultaneous activation of the HMGB1/RAGE/NF-κB and F2/Rho signaling pathways plays a critical role in hypoxia-induced inflammatory responses and coagulation abnormalities, and provides a theoretical basis for the development of potential therapeutic strategies.

show abstract

Section: Introductionmentioning

confidence: 99%

Inflammation and coagulation abnormalities via the activation of the HMGB1‑RAGE/NF‑κB and F2/Rho pathways in lung injury induced by acute hypoxia

Zhang¹,

Yan²,

Ge³

et al. 2023

Int J Mol Med

View full text Add to dashboard Cite

show abstract

“…RAGE is an MHC class III encoded protein belonging to the immunoglobulin (Ig) superfamily that was initially recognized as a receptor for advanced glycation end products (AGEs); however, it rapidly became revealed that this receptor has a multitude of ligands, including S100 proteins such as S100B, S100A4, S100A7, S100A8/A9, S100A11, S100A12, HMGB1, amyloid β peptide, prothrombin, chondroitin sulfate E, heparan sulfate, heparin and the complement C1q and C3a components [ 140 , 333 , 334 , 335 , 336 , 337 , 338 ]. Additional RAGE ligands include the neutrophil cationic antimicrobial protein CAP37 and the neutrophil proteases: CathG, NE and PR3 [ 227 , 238 , 339 ].…”

Section: Pro-tumor Function Of Ragementioning

confidence: 99%

Leveling Up the Controversial Role of Neutrophils in Cancer: When the Complexity Becomes Entangled

Sionov

2021

Cells

View full text Add to dashboard Cite

Neutrophils are the most abundant immune cell in the circulation of human and act as gatekeepers to discard foreign elements that have entered the body. They are essential in initiating immune responses for eliminating invaders, such as microorganisms and alien particles, as well as to act as immune surveyors of cancer cells, especially during the initial stages of carcinogenesis and for eliminating single metastatic cells in the circulation and in the premetastatic organs. Since neutrophils can secrete a whole range of factors stored in their many granules as well as produce reactive oxygen and nitrogen species upon stimulation, neutrophils may directly or indirectly affect carcinogenesis in both the positive and negative directions. An intricate crosstalk between tumor cells, neutrophils, other immune cells and stromal cells in the microenvironment modulates neutrophil function resulting in both anti- and pro-tumor activities. Both the anti-tumor and pro-tumor activities require chemoattraction towards the tumor cells, neutrophil activation and ROS production. Divergence is seen in other neutrophil properties, including differential secretory repertoire and membrane receptor display. Many of the direct effects of neutrophils on tumor growth and metastases are dependent on tight neutrophil–tumor cell interactions. Among them, the neutrophil Mac-1 interaction with tumor ICAM-1 and the neutrophil L-selectin interaction with tumor-cell sialomucins were found to be involved in the neutrophil-mediated capturing of circulating tumor cells resulting in increased metastatic seeding. On the other hand, the anti-tumor function of neutrophils was found to rely on the interaction between tumor-surface-expressed receptor for advanced glycation end products (RAGE) and Cathepsin G expressed on the neutrophil surface. Intriguingly, these two molecules are also involved in the promotion of tumor growth and metastases. RAGE is upregulated during early inflammation-induced carcinogenesis and was found to be important for sustaining tumor growth and homing at metastatic sites. Cathepsin G was found to be essential for neutrophil-supported lung colonization of cancer cells. These data level up the complexity of the dual role of neutrophils in cancer.

show abstract

“…Peptide mixtures were analyzed in duplicate by nano-LC-HRMS as described by Degani et al with few modifications in the multi-step separative gradient [26]. Briefly, for each sample, 5 µL of solubilized peptides in 0.1% TFA were injected onto the Acclaim PepMap C18 column (75 µm × 15 cm, 100 Å pore size), protected by a pre-column (Acclaim PepMap, 100 µm × 2 cm, 100 Å pore size), both from Thermo Scientific (Milan, Italy).…”

Section: Nano Hplc-hrms Analysismentioning

confidence: 99%

Chromatographic Characterization and In Vitro Bioactivity Evaluation of Lactobacillus helveticus Hydrolysates upon Fermentation of Different Substrates

et al. 2021

View full text Add to dashboard Cite

Among various food sources, milk proteins remain the major vector for functional peptides endowed with several biological activities. Particularly, the proteolytic activity of lactic acid bacteria during milk fermentation has been one of the most followed strategies to produce bioactive peptides. In the present study, the exploration of the activity of several starter cultures, at different fermentation times, was firstly investigated by reversed phase-high performance liquid chromatography. Among the tested strains, Lactobacillus helveticus showed a higher proteolytic activity and it was submitted to further investigations by changing the fermentation substrate (skim milk, brain heart infusion, peptone water) as well as the extraction strategy (trichloroacetic acid vs. glass beads). The chromatographic analyses and the in vitro antioxidant and antihypertensive assays highlighted considerable differences for L. helveticus hydrolysates from different substrates, while a negligible impact by the two extraction protocols emerged. Furthermore, nano-high pressure liquid chromatography coupled with a high resolution mass spectrometry analyzer allowed the preliminary discrimination of fractions from fermented skim milk, likely responsible for the found activity. The obtained results suggest the possibility of varying the fermentation parameters in order to maximize the functional effects of the bioactive peptides.

show abstract

Prothrombin is a binding partner of the human receptor of advanced glycation end products

Cited by 6 publications

References 55 publications

Inflammation and coagulation abnormalities via the activation of the HMGB1‑RAGE/NF‑κB and F2/Rho pathways in lung injury induced by acute hypoxia

Inflammation and coagulation abnormalities via the activation of the HMGB1‑RAGE/NF‑κB and F2/Rho pathways in lung injury induced by acute hypoxia

Leveling Up the Controversial Role of Neutrophils in Cancer: When the Complexity Becomes Entangled

Chromatographic Characterization and In Vitro Bioactivity Evaluation of Lactobacillus helveticus Hydrolysates upon Fermentation of Different Substrates

Contact Info

Product

Resources

About