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Inherited Differences in Alpha1-Antitrypsin
Published in Stephen D. Litwin, Genetic Determinants of Pulmonary Disease, 2020
Antiproteolytic activity in mammalian sera is not a new observation; it was first observed by investigators during the last century [4,5]. Advances in protein chemistry have revealed that this activity is due to a group of individual inhibitors. Human serum alone contains seven distinct major protease inhibitors (Table 1) which differ in their specificity range. For example, alpha2macroglobulin shows a broad spectrum of inhibition which includes proteases with different mechanisms of action such as trypsin and papain [6]. Alpha1antichymotrypsin neutralizes only chymotrypsin and chymotrypsin-like enzymes; it does not inhibit trypsin. The recently described anti-collagenase is apparently quite specific [7]. Other enzymes have not been extensively tested. The major inhibitors present in human sera are listed in Table 1.
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.
Primary Hyperfibrino(Geno)Lytic Syndromes
Published in Genesio Murano, Rodger L. Bick, Basic Concepts of Hemostasis and Thrombosis, 2019
Rodger L. Bick, Genesio Murano
Primary hyperfibrino(geno)lysis usually occurs in well-defined clinical entities in which there is direct or indirect activation of plasminogen into systemically circulating plasmin. In most disorders, the precise mechanism by which this occurs is not known. In several types of malignancies, tumor extracts are capable of activating the fibrinolytic system either directly or indirectly. In other disorders, mechanisms that may be involved include poor hepatic clearance of plasminogen activators or a decrease or dysfunction of inhibitors such as the alpha-2-macroglobulin fraction.7 In chronic liver disease, alpha-2-macroglobulin is often increased, but appears to lose significant biologic function in inhibiting the fibrinolytic system. Table 1 lists various mechanisms through which the fibrinolytic system could be activated. Figure 1 depicts the pathophysiology of primary hyperfibrino(geno)lysis.
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].
A single exposure to eucalyptus smoke sensitizes rats to the postprandial cardiovascular effects of a high carbohydrate oral load
Published in Inhalation Toxicology, 2020
Brandi L. Martin, Leslie C. Thompson, Yong Ho Kim, Samantha J. Snow, Mette C. Schladweiler, Pamela Phillips, Molly Harmon, Charly King, Judy Richards, Ingrid George, Najwa Haykal-Coates, M. Ian Gilmour, Urmila P. Kodavanti, Mehdi S. Hazari, Aimen K. Farraj
Serum samples were measured for insulin (Millipore, Billerica, MA), alpha(1)-acid glycoprotein (AGP) and alpha-2-macroglobulin (A2M) (rat Acute Phase Protein Panel 1, Meso Scale Discovery, Rockville, MD). Alpha (1)-acid glycoprotein and alpha-2-macroglobulin are prominent acute phase proteins in rats (Cray et al. 2009). We also measured various cytokines in serum (i.e. TNF-alpha, IL-6, IL-1beta, IFN-gamma, IL-4, IL-5, IL-10, IL-13, and keratinocyte chemoattractant (KC)/growth-regulated oncogene (KC-GRO); V-PLEX Proinflammatory Panel 2 Rat kit, Meso Scale Discovery, Rockville, MD) according to the manufacturer’s protocol. We selected this panel of cytokines in part because we previously determined that exposure to air pollution modifies levels of IL-4 (Henriquez et al. 2017) and separately IL-6 and TNF-alpha (Henriquez et al. 2018). Plasma samples were used to measure adrenaline (Rocky Mountain Diagnostics, Colorado Springs, CO) and corticosterone (Arbor Assays, Ann Arbor, MI), according to the manufacturer’s protocol.
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.