Polyamine‐promoted autoactivation of plasma hyaluronan‐binding protein

Abstract

See also Kanse SM, Etscheid M. Factor VII activating protease (FSAP): caught in the cross-fire between polycations and polyanions. This issue, pp 556-8.

Histone H4 Promotes Prothrombin Autoactivation

“…Other zymogens autoactivate upon interaction with external cofactors. Hyaluronan-binding protein (factor VII activating protease) autoactivates upon binding of histones (8), negatively charged molecules such as heparin and RNA (9, 29, 38 -40), and spermidine (41). Coagulation factors XI and XII autoactivate upon binding of RNA (9).…”

Inhibition of Plasma Hyaluronan-Binding Protein Autoactivation by Laccaic Acid

“…Alternatively, negatively charged molecules (such as heparin and RNA) and positively charged molecules (such as polyamines) dramatically promote pro-PHBP autoactivation. [7][8][9] Hence it has been postulated that these molecules contribute to physiological pro-PHBP activation. The mechanism of the action of polyamines is to promote the formation of the pro-PHBP autoactivation complex, 8) while heparin and RNA might act as a scaffold for the accumulation of pro-PHBP.…”

“…[7][8][9] Hence it has been postulated that these molecules contribute to physiological pro-PHBP activation. The mechanism of the action of polyamines is to promote the formation of the pro-PHBP autoactivation complex, 8) while heparin and RNA might act as a scaffold for the accumulation of pro-PHBP. 9) Thus pro-PHBP activation can proceed through multiple mechanisms depending on the kind of pathophysiological stimuli.…”

“…9) Thus pro-PHBP activation can proceed through multiple mechanisms depending on the kind of pathophysiological stimuli. 8,9) It has been suggested that PHBP plays roles in the regulation of inflammation, 10) vascular function, 11) neointima formation, 12) liver fibrosis, 13) and atherosclerosis. 11,14) Therefore, a compound that regulates pro-PHBP activation might contribute to pharmacological control of the progression of these diseases.…”

“…15) However, bikaverin, at concentrations slightly higher than the concentration which affected pro-PHBP autoactivation, inhibited the enzymatic activities of other serine proteases. 15) To identify a more selective inhibitor, we screened a panel of compounds related to bikaverin, and identified three anthraquinone compounds, purpurin, 15) carminic acid, 8) and a lac dye (a mixture of laccaic acids). In this report, we describe the action of laccaic acid.…”