China
Africa
Explore chapters and articles related to this topic
Regulation of α1-Acid glycoprotein genes and Relationship to Other Type 1 Acute Phase Plasma Proteins
Published in Andrzej Mackiewicz, Irving Kushner, Heinz Baumann, Acute Phase Proteins, 2020
Heinz Baumann, Karen R. Prowse, Kwang-Ai Won, Sanja Marinkovic-Pajovic
α1-Acid glycoprotein (AGP), also known as orosomucoid, is a plasma protein that has caught the attention of various scientists: biochemists, because of its high degree of carbohydrate heterogeneity; physiologists, because of its elusive function as a major acute phase protein; molecular biologists, because of its multihormone-responsive and tissue- and developmental-specific expression pattern; and geneticists, because of species-specific gene duplication events.1 The acute phase-mediated change in AGP gene activity in liver cells was found in several species to be of impressive magnitude and proved to be evolutionarily conserved in vertebrates. The elucidation of the molecular events involved in AGP gene expression was aimed at defining regulatory mechanisms that were also applicable to other acute phase plasma protein genes. Indeed, several independent studies on AGP genes have uncovered regulatory features that were general to acute phase protein genes (e.g., cytokine regulatory elements and trans-acting factors), but also that were unique (e.g., mechanism of glucocorticoid regulation).
Transport of Protein-Bound Radiotracers Into Tissues*
Published in Lelio G. Colombetti, Biological Transport of Radiotracers, 2020
Unlike the hormone-binding globulins, orosomucoid is commercially available in pure form. The effects of physiological concentrations of orosomucoid on BBB propranolol transport have been studied.117 The apparent free fraction in vivo is greater than the free fraction in vitro, e.g., the concentration of orosomucoid which inhibits BBB transport of propranolol 50% is ∿25 μM vs. the level of orosomucoid which binds 50% of the drug in vitro, 3.3 μM.117 Given In KD (app)/KD = k3t (Equation 8), and KD (app) = 25 μM and KD = 3.3 μM, then k3t = 2.0. This estimate of k3t is comparable to that of corticosterone (Table 6), which is to be expected since the permeability of the BBB to propranolol and corticosterone is comparable.
Pregnancy-Related Proteins in Non-Trophoblastic Tumors
Published in Gábor N. Than, Hans Bohn, Dénes G. Szabó, Advances in Pregnancy-Related Protein Research, 2020
Not long afterwards, lino et al.189 reported elevated levels of IGF-BP-1, which they previously designated PP12, in the serum of patients with ovarian cancer, and also confirmed that immunohistochemical tests showed positive tissue staining for PP12 in 57% of cervical epidermoid cancer cases.161 Briese et al.57 noted significantly elevated serum concentrations of IGF-BP-1 in 83 bronchial cancers at stages II-IV. They found the predictive value of IGF-BP-1 with respect to tumorous diseases to be 86%, with a sensitivity of 58%, a specificity of 58%, and a precision of 69%. Elevated circulating levels of orosomucoid, AFP, and IGF-BP-1 demonstrably accompanied the disease, while SP1 α2-PAG and PP10 did not.
Surface charge, glycocalyx, and blood-brain barrier function
Published in Tissue Barriers, 2021
Fruzsina R. Walter, Ana R. Santa-Maria, Mária Mészáros, Szilvia Veszelka, András Dér, Mária A. Deli
There are no direct measurements available on how negatively charged polyanions like GAGs and GAG mimetics change the surface charge of endothelial cells. We hypothesize, that this might be the case from indirect experimental evidences. The polyanion GAG heparin reversed the disappearance of anionic sites from the luminal surface of brain capillaries when given after protamine treatment.7 A medicine containing natural GAGs, sulodexide, increased the thickness of glycocalyx in sublingual and retinal microvessels in patients.48 These data suggest an increased charge selectivity, which was proven experimentally for other polyanions. Orosomucoid or α-1-acid glycoprotein is a negatively charged plasma protein overexpressed in pathologies, like inflammation and hypertension. Orosomucoid, which is essential for capillary charge selectivity, is produced by human microvascular endothelial cells and exerts a protective effect by interacting with other components of the endothelial glycocalyx.49 When orosumucoid was present in the permeability assay buffer the permeability of the positively charged ribonuclease (14 kDa) was increased and the transfer of the negatively charged lactalbumin (14 kDa) was decreased in a mouse brain endothelial cell line model and in murine pial microvessels.50,51 Another study using a primary rat BBB model found a decrease in the permeability of the negatively charged small paracellular marker fluorescein (0.4 kDa) after orosomucoid treatment.52 In addition to charge effects, this barrier tightening was mediated by increased expression of tight junction proteins occludin and ZO-1.52
Urinary orosomucoid is associated with diastolic dysfunction and carotid arteriopathy in the general population. Cross-sectional data from the Tromsø study
Published in Scandinavian Cardiovascular Journal, 2022
Runa M. Andreassen, Jens B. Kronborg, Henrik Schirmer, Ellisiv B. Mathiesen, Toralf Melsom, Bjørn O. Eriksen, Trond G. Jenssen, Marit D. Solbu
Orosomucoid (molecular weight 41kD, negatively charged) is a nonspecific acute inflammatory protein mainly produced in the liver, but also in endothelial cells and other extra-hepatic tissue [6]. Orosomucoid is found among other plasma proteins as well as glycosaminoglycans and proteoglycans in the endothelial surface layer, a cell coat that covers the luminal side of the endothelium throughout the vasculature. The endothelial surface layer protects the vessel wall from contact with blood constituents and is important for the maintenance of normal glomerular permselectivity. Damage to this layer is believed to be a direct cause of albuminuria and to be involved in the development of atherosclerotic vascular disease [7–10].
Body fat percentage is more strongly associated with biomarkers of low-grade inflammation than traditional cardiometabolic risk factors in healthy young adults – the Lifestyle, Biomarkers, and Atherosclerosis study
Published in Scandinavian Journal of Clinical and Laboratory Investigation, 2019
Paul Pettersson-Pablo, Torbjörn K. Nilsson, Lars H. Breimer, Anita Hurtig-Wennlöf
While both CRP and orosomucoid are acute-phase reactants produced by the liver and increase in response to inflammatory signaling, their respective functions differ: CRP is a complement activator binding to bacteria and host cells, and is considered a possible mediator in atherosclerotic pathophysiology [5]. In contrast to CRP, orosomucoid increases more slowly in inflammatory states, but remains elevated for a prolonged period [10, 25]. CRP may thus be a more straightforward marker of acute inflammatory load, whereas elevations in orosomucoid, which is synthesized by both and adipocytes and hepatocytes under different conditions [11], may reflect both adipocyte immunomodulatory signaling induced by metabolic dysregulation in adiposity, and cytokine driven hepatic synthesis in response to inflammation [11]. CRP and orosomucoid are both independent predictors of future cardiovascular risk [26, 27], a relationship consistent with evidence indicating inflammation as a key regulatory process uniting multiple risk factors, including obesity, to the alterations of vascular function seen in atherosclerosis [28]. The detrimental effects of obesity may begin early in life, and childhood obesity is known to be associated with an increased cardiovascular risk in adulthood [29]. Previously, an increase in circulating inflammatory chemokines was found to correlate with preatherosclerotic vascular alterations in young, healthy children [30]. Evidence indicates inflammation as the common, mechanistic link between obesity and atherosclerosis [31]. Adipokine release from adipose tissue is associated with endothelial dysfunction and systemic inflammation, which are both features characteristic of atherosclerosis [32]. Similar patterns of inflammatory cell accumulation, in particular a recruitment of a heterogeneous macrophage population associated with cell death and T-cell activation are prominent features of both obesity and atherosclerosis [28]. Such relationships between adiposity and inflammation provide an explanation for the strong association seen in our population between an increased body fat and inflammatory biomarkers.