China
Africa
Explore chapters and articles related to this topic
Transformin Growth Factor-β
Published in Jason Kelley, Cytokines of the Lung, 2022
Free TGF-β in serum binds to alpha2-macroglobulin as well as to circulating fibronectin (Danielpour and Sporn, 1990). Binding to fibronectin does not inactivate TGF-β, but binding to alpha2-macroglobulin in serum does. Moreover, binding to alpha2-macroglobulin differentially modulates the activity of TGF-β1 and TGF-β2 (Danielpour and Sporn, 1990). Possibly, binding to alpha2-macroglobulin represents a first step in the inactivating and clearing of free TGF-β which moves away from its intended site of action. alpha2-Macroglobulin, its receptor, and proteases in the liver appear to function as a concerted system to clear TGF-β rapidly (t1/2 4 min) from serum (LaMarre et al., 1991).
Cystic Fibrosis
Published in Stephen D. Litwin, Genetic Determinants of Pulmonary Disease, 2020
Alexander G. Bearn, Β. Shannon Danes
In 1972, Rao and Nadler reported the deficiency of a proteolytic activity with arginine esterase specificity in saliva [56] and plasma [57,58] of patients with CF, suggesting that the various "factors" present in CF resulted from a deficiency of this proteolytic activity. Wilson and Fudenberg then demonstrated [34] a deficiency of an alpha2-macroglobulin (α2M) fragment in plasma of patients with CF and obligatory heterozygotes when compared to controls, postulating that an abnormality in the binding affinity of the α2M for plasma proteases might account for the presence of the CF factors. Shapira and colleagues documented the absence of α2M-protease complex in plasma of patients with CF [59] and the reduced binding of α2M from patients to papain, trypsin, and thrombin treatment [60]. Since papain and trypsin are not plasma endopeptidases, they hypothesized that the absence of α2-protease complex in CF is due to a molecular defect in the macroglobulin making it functionally abnormal [60]. All of these reports are difficult to interpret; more work is needed.
Coagulation Theory, Principles, and Concepts
Published in Harold R. Schumacher, William A. Rock, Sanford A. Stass, Handbook of Hematologic Pathology, 2019
Alpha-2-macroglobulin is a plasma proteinase inhibitor with wide specificity. Structurally alpha-2-macroglobulin is composed of four identical subunits arranged as a pair of dimers. Alpha-2-macroglobulin is an inhibitor of many of the components of the fibrinolytic system. It inactivates plasmin, kallikrein, two-chain urokinase, tPA, and the streptokinase-plasminogen complex (102). Alpha-2-macroglobulin is not related to the typical serine protease family of inhibitors referred to as “serpins.” Structurally it is related to the complement proteins C3 and C4.
Serum proteome assessment in nonalcoholic fatty liver disease in children: a preliminary study
Published in Expert Review of Proteomics, 2020
Paweł Małecki, Joanna Tracz, Magdalena Łuczak, Magdalena Figlerowicz, Katarzyna Mazur-Melewska, Wojciech Służewski, Anna Mania
The importance of alpha-2-macroglobulin (α2 MG) in liver disease has been evaluated concerning various liver diseases. Initial research concerned patients with hepatitis B and C. Currently, three indicators of hepatic fibrosis are used, which take into account the concentration of this protein – FibroTest, FibroSPECT, Hepascore. Significantly higher alpha-2-macroglobulin levels were described in patients with advanced fibrosis (METAVIR F3-F4) [35,36]. In our study group, the concentration of this protease inhibitor, as well as the other one – alpha-1-antitrypsin, was significantly lower in NAFLD patients than in the control group. The reason for the observed condition may be reduced production of α2 MG by the affected liver or a decrease in concentration associated with consumption – α2 MG binds cytokines such as interleukin-6 (Il-6) and TNF-α, which level in NAFLD is elevated [37].
Identification of the differentially expressed protein biomarkers in rat blood plasma in response to gamma irradiation
Published in International Journal of Radiation Biology, 2020
Jia-Li Sun, Shuang Li, Xue Lu, Jiang-Bin Feng, Tian-Jing Cai, Mei Tian, Qing-Jie Liu
Alpha-2-macroglobulin (A2m) is a protease inhibitor and cytokine transporter encoded gene which has been highly conserved between different species (Calvert et al. 2019). A2m has many diversity and complex functions, but it is primarily known by its ability to inhibit a broad spectrum of proteases without the direct blockage of the protease active site (Rehman et al. 2013). In addition, A2m protein can also binds to some growth factors and cytokines, including TNF-α, IL-1β and IL-6, as a carrier protein. Previous studies indicated that A2m was involved in the process of inflammation, cancer and neurodegenerative diseases (Calvert et al. 2019; Guo et al. 2019a; Ma et al. 2019). Recently, ionizing radiation-induced A2m protein expression in non-human primates was shown to have dose-dependent changes, which could be used as a candidate for radiation biomarker (Byrum et al. 2017). In addition, it has been reported that A2m was identified as a reliable predictive biomarker for radiation-induced lung inflammation using a bioinformatics approach (Oh et al. 2011). Our results also suggested that the expression levels of A2m protein in rat blood plasma were significantly increased with dose at 3 and 5 days after radiation exposure. Current findings elucidated that A2m might play an important role in the response to radiation exposure.
Advances in the proteomics of amniotic fluid to detect biomarkers for chromosomal abnormalities and fetomaternal complications during pregnancy
Published in Expert Review of Proteomics, 2019
Aayushi Vasani, Maushmi S. Kumar
IUGR is a condition of an unborn baby, being smaller due to less growth rate than a normal baby inside the womb. IUGR carries an increased risk of mortality and morbidity. Identification is crucial because proper evaluation and management can result in favorable outcomes. Decreased IUG may have a negative effect on brain and mental development [59]. First attempt on proteomics approach of IUGR has been done in 1998 where they discovered reduced glycosylation of 2HS glycoprotein in cord plasma [60]. Proteins like transferrin cause Cu and Fe metabolism, and ceruloplasmin acts as circulating ferroxidase enzyme able to oxidize ferrous ions together acting as anti-oxidative system [61]. Down-regulation of both proteins causes fetal growth retardation [62]. High blood ferritin levels can also be a cause of IUGR [63]. It was observed that fibrinogen was up-regulated in the amniotic fluid which causes obstetric complications during pregnancy forming clots in the body [64]. Alpha-2-macroglobulin (α2M) which causes coagulation was also detected [65,66]. Due to the immune response in the body, there are a cascade of complement proteins like C3, C3b, C3c, and C4 participating in innate immunity and are crucial intermediates in the first trimester. Proteins controlling blood pressure, and iron copper homeostasis show some abnormality. For blood pressure, angiotensinogen is up-regulated and kininogen is down-regulated in the first 20 weeks of gestation [67,68].