Actin is a noncompetitive plasmin inhibitor.

Area of Science:

• Biochemistry
• Cell Biology
• Physiology

Background:

• Actin is a highly abundant cellular protein found at micromolar concentrations in peripheral blood.
• Actin released from dying cells can become trapped in fibrin clots at sites of tissue injury.

Purpose of the Study:

• To investigate the effects of actin on fibrin clot lysis.
• To determine the mechanism by which actin influences plasmin activity.

Main Methods:

• Incorporation of native rabbit skeletal muscle actin into fibrin clots.
• Assay of plasmin's hydrolysis of a synthetic substrate (S-2251) in the presence of actin.
• Testing the effect of epsilon-aminocaproic acid and tranexamic acid on actin-plasmin interaction.
• Evaluating the influence of plasma actin-binding proteins (gelsolin, vitamin D-binding protein) on actin's inhibition of plasmin.

Main Results:

• Actin incorporation into fibrin clots significantly slowed clot lysis.
• Actin inhibited plasmin's hydrolysis of S-2251 in a noncompetitive manner (Ki = 0.6-3.1 microM).
• Inhibition was rapid, but no covalent actin-plasmin complexes formed.
• Epsilon-aminocaproic acid and tranexamic acid blocked actin's inhibition of plasmin, indicating interaction with lysine-binding sites.
• Plasma actin-binding proteins did not prevent actin from inhibiting plasmin.

Conclusions:

• Extracellular actin can inhibit fibrin clot lysis.
• Actin modulates plasmin activity, likely through interactions with plasmin's lysine-binding regions.
• These findings suggest a role for actin in regulating plasmin-dependent biological responses at sites of inflammation and tissue injury.