Apolipoprotein H
Apolipoprotein H (Apo-H), previously known as (β2-glycoprotein I, beta-2 glycoprotein I), is a multifunctional apolipoprotein. One of its functions is to bind cardiolipin. When bound the structure of cardiolipin and Apo-H both undergo large changes in structure.[1] Within the structure of Apo-H is a stretch of positively charged amino acids, (protein sequence positions 282-287) Lys-Asn-Lys-Glu-Lys-Lys, are involved in phospholipid binding (See image on right).[2]
Apo-H has a complex involvement in agglutination, it appears to alter ADP mediated agglutenation of platlets.[3] Normally Apo-H assumes an anti-coagulation activity in serum (by inhibiting coagulation factors), however changes in blood factors can result of a reversal of that activity.
Inhibitory activities
Apo-H appears to completely inhibit serotonin release by the platelets[4] and prevents subsequent waves of the ADP-induced aggregation. The activity of Apo-H appears to involve the binding of agglutinating, negatively charged compounds, and inhibits agglutination by the contact activation of the intrinsic blood coagulation pathway. [5] Apo-H causes a reduction of the prothrombinase binding sites on platelets and reduces the activation caused by collagen when thrombin is present at physiological serum concentrations of Apo-H suggesting a regulatory role of Apo-H in coagulation.[6]
Apo-H also inhibits the generation of factor Xa in the presence of platelets.[7] Apo-H also inhibits that activation of factor XIIa.[8]
In addition, Apo-H inhibits the activation of protein C blocking its activity on phosphatidylserine:phosphatidylcholine vesicles[9] however once protein C is activated, Apo-H fails to inhibit activity. Since protein C is involved in factor Va degradation Apo-H indirectly inhibits the degradation of factor Va. [10] This inhibitory activity was diminished by adding phospholipids suggesting the Apo-H inhibition of protein C is phospholipid competitive.[11] This indicates that under certain conditions Apo-H takes on a procoagulation properties.
Pathology
Anti-cardiolipin antibodies are found in both infectious (syphilis) and autoimmune disease (sclerosis, lupus).[12] The activity of anti-cardiolipin antibodies in autoimmune antiphospholipid syndrome requires apolipoprotein H.[13][14] The subset of antibodies that bind Apo-H and alter its activity are condsidered different from antibodies that bind thrombin, serum phospholipids and are called anti-apolipoprotein antibodies. In autoimmune disease, anti-apolipoprotein antibodies (Anti β2 glycoprotein I antibodies) strongly associate with thrombotic forms of lupus and sclerosis.
References
- ^ Borchman D, Harris EN, Pierangeli SS, Lamba OP (1995). "Interactions and molecular structure of cardiolipin and beta 2-glycoprotein 1 (beta 2-GP1)". Clin. Exp. Immunol. 102 (2): 373–8. doi:10.1111/j.1365-2249.1995.tb03792.x. PMC 1553418. PMID 7586693. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1553418.
- ^ Sheng Y, Sali A, Herzog H, Lahnstein J, Krilis SA (1996). "Site-directed mutagenesis of recombinant human beta 2-glycoprotein I identifies a cluster of lysine residues that are critical for phospholipid binding and anti-cardiolipin antibody activity". J. Immunol. 157 (8): 3744–51. PMID 8871678.
- ^ Nimpf J, Wurm H, Kostner GM (1985). "Interaction of beta 2-glycoprotein-I with human blood platelets: influence upon the ADP-induced aggregation". Thromb. Haemost. 54 (2): 397–401. PMID 4082080.
- ^ Nimpf J, Wurm H, Kostner GM (1987). "Beta 2-glycoprotein-I (apo-H) inhibits the release reaction of human platelets during ADP-induced aggregation". Atherosclerosis 63 (2–3): 109–14. doi:10.1016/0021-9150(87)90110-9. PMID 3827975.
- ^ Schousboe I (1985). "beta 2-Glycoprotein I: a plasma inhibitor of the contact activation of the intrinsic blood coagulation pathway". Blood 66 (5): 1086–91. PMID 4052628.
- ^ Nimpf J, Bevers EM, Bomans PH, et al. (1986). "Prothrombinase activity of human platelets is inhibited by beta 2-glycoprotein-I". Biochim. Biophys. Acta 884 (1): 142–9. PMID 3768409.
- ^ Shi W, Chong BH, Hogg PJ, Chesterman CN (1993). "Anticardiolipin antibodies block the inhibition by beta 2-glycoprotein I of the factor Xa generating activity of platelets". Thromb. Haemost. 70 (2): 342–5. PMID 8236146.
- ^ Schousboe I, Rasmussen MS (1995). "Synchronized inhibition of the phospholipid mediated autoactivation of factor XII in plasma by beta 2-glycoprotein I and anti-beta 2-glycoprotein I". Thromb. Haemost. 73 (5): 798–804. PMID 7482406.
- ^ Keeling DM, Wilson AJ, Mackie IJ, Isenberg DA, Machin SJ (1993). "Role of beta 2-glycoprotein I and anti-phospholipid antibodies in activation of protein C in vitro". J. Clin. Pathol. 46 (10): 908–11. doi:10.1136/jcp.46.10.908. PMC 501616. PMID 8227406. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=501616.
- ^ Matsuda J, Gohchi K, Kawasugi K, Gotoh M, Saitoh N, Tsukamoto M (1995). "Inhibitory activity of anti-beta 2-glycoprotein I antibody on factor Va degradation by activated-protein C and its cofactor protein S". Am. J. Hematol. 49 (1): 89–91. doi:10.1002/ajh.2830490116. PMID 7741146.
- ^ Mori T, Takeya H, Nishioka J, Gabazza EC, Suzuki K (1996). "beta 2-Glycoprotein I modulates the anticoagulant activity of activated protein C on the phospholipid surface". Thromb. Haemost. 75 (1): 49–55. PMID 8713779.
- ^ Kumar KS, Jyothy A, Prakash MS, Rani HS, Reddy PP (2002). "Beta2-glycoprotein I dependent anticardiolipin antibodies and lupus anticoagulant in patients with recurrent pregnancy loss". Journal of postgraduate medicine 48 (1): 5–10. PMID 12082318.
- ^ McNeil HP, Simpson RJ, Chesterman CN, Krilis SA (1990). "Anti-phospholipid antibodies are directed against a complex antigen that includes a lipid-binding inhibitor of coagulation: beta 2-glycoprotein I (apolipoprotein H)". Proc. Natl. Acad. Sci. U.S.A. 87 (11): 4120–4. doi:10.1073/pnas.87.11.4120. PMC 54059. PMID 2349221. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=54059.
- ^ Hunt JE, McNeil HP, Morgan GJ, Crameri RM, Krilis SA (1992). "A phospholipid-beta 2-glycoprotein I complex is an antigen for anticardiolipin antibodies occurring in autoimmune disease but not with infection". Lupus 1 (2): 75–81. doi:10.1177/096120339200100204. PMID 1301967.
External links
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| Apolipoproteins |
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| Lipoproteins |
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| Extracellular enzymes |
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| Lipid transfer proteins |
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| Cell surface receptors |
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| ATP-binding cassette transporter |
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mt, k, c/g/r/p/y/i, f/h/s/l/o/e, a/u, n, m
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k, cgrp/y/i, f/h/s/l/o/e, au, n, m, epon
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m(A16/C10),i(k, c/g/r/p/y/i, f/h/s/o/e, a/u, n, m)
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| Mucoproteins |
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| Proteoglycans |
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| Other |
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mt, k, c/g/r/p/y/i, f/h/s/l/o/e, a/u, n, m
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k, cgrp/y/i, f/h/s/l/o/e, au, n, m, epon
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m(A16/C10),i(k, c/g/r/p/y/i, f/h/s/o/e, a/u, n, m)
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biochemical families: prot · nucl · carb (glpr, alco, glys) · lipd (fata/i, phld, strd, gllp, eico) · amac/i · ncbs/i · ttpy/i
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