Role of plasma gelsolin and the vitamin D-binding protein in clearing actin from the circulation.

Lind, Stuart E.; Smith, David B.; Janmey, Paul A.; Stossel, Thomas P.

doi:10.1172/jci112634

Cited by 152 publications

(99 citation statements)

References 35 publications

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“…Plasma gelsolin (MW 93kD) contains an additional 25-amino acid residue at the amino terminus and is believed to be primarily secreted by muscle cells (29). It functions as an actin scavenger by binding actin in the circulation (26), then the complex is cleared by the reticular endothelial system (30). Gelsolin also functions as a lipid carrier with strong binding affinity to several cystolic and plasma lipids such as phosphotidylinositol, lipopolysaccharide, and lysophosphatidic acid (11,12).…”

Section: Discussionmentioning

confidence: 99%

Gelsolin is Depleted in Post-Shock Mesenteric Lymph

Jordan

Moore

Damle

et al. 2007

Journal of Surgical Research

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Background-Gelsolin is a plasma protein that functions to depolymerize actin filaments preventing capillary plug formation following tissue injury. It also functions to mediate the inflammatory response by binding proinflammatory lipids such as lysophosphatidic acid, sphingosine-1-phosphate and phosphoinositides. Clinically, reduced gelsolin concentrations have been associated with increased mortality in critically ill, trauma and burn patients. We have previously shown that following hemorrhagic shock with splanchnic hypoperfusion, mesenteric lymph contains lipid components that cause neutrophil and EC activation and that protein concentrations are severely diluted due to resuscitation. We hypothesized that lipid binding proteins such as gelsolin may be depleted after trauma/hemorrhagic shock leading to increased lipid bioactivity.

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Section: Discussionmentioning

confidence: 99%

Gelsolin is Depleted in Post-Shock Mesenteric Lymph

Jordan

Moore

Damle

et al. 2007

Journal of Surgical Research

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“…6 It includes the plasma proteins gelsolin, which depolymerizes polymeric (filamentous) actin, and Gc-globulin, which binds avidly to monomeric actin to form an atoxic complex that is then eliminated from the bloodstream. 11 Gelsolin is synthesized in skeletal muscle, whereas Gc-globulin is produced in the liver. In ALF, the capacity of the EASS may be overwhelmed by the combination of actin release from necrotic hepatocytes and reduced production of Gcglobulin.…”

mentioning

confidence: 99%

Temporal profile of total, bound, and free Gc-globulin after acetaminophen overdose

Schiødt¹,

Ott²,

Tygstrup³

et al. 2001

Liver Transplantation

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Low admission values of the actin scavenger Gc-globulin are associated with an adverse outcome in acetaminophen (paracetamol) overdose. This prospective longitudinal study including 84 patients with acetaminophen overdose characterizes the temporal profile of Gc-globulin during the entire length of hospitalization. Serum Gc-globulin (total, actin bound, and free) levels and actin-complex ratio were measured on admission and every 12 hours until discharge. In 32 patients without hepatotoxicity (non-HEPTOX group; peak transaminase levels < 1,000 U/L), total and free Gc-globulin levels and complex ratio remained within normal range during hospitalization. Among 52 patients with hepatotoxicity (HEPTOX group; peak transaminase levels > 1,000 U/L), 15 patients had hepatic encephalopathy (HE), and 37 patients did not. In these 2 groups, total and free Gc-globulin levels decreased to 97 and 50 mg/L and 148 and 86 mg/L, respectively (normal mean, 340 and 299 mg/L), the nadir occurring at 72 hours postoverdose. Complex ratio peaked at 60 hours at levels more than 3-fold greater than normal. Conversely, bound Gc-globulin remained within normal levels for all patients throughout the observation period. At day 2, a total Gc-globulin cutoff value of less than 120 mg/L correctly predicted HE in 75%, and a value greater than 120 mg/L correctly predicted the absence of HE in 91% of patients. In conclusion, Gc-globulin is severely stressed in patients with hepatotoxicity. Extreme values occurred at 60 to 72 hours postoverdose, a period in which Gc-globulin protection against actin toxicity may be inadequate. A total Gc-globulin level less than 120 mg/L on day 2 is a good predictor of later HE. Bound Gc-globulin is maintained at constant levels independent of total Gc-globulin levels, suggesting a balanced upregulation of the removal of bound Gc-globulin even under conditions with increased actin release. (Liver Transpl 2001;7:732-738.)

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“…However, when actin was added to the serumcontaining medium, haemolytic activity increased significantly. Serum contains the actin-binding and scavenger proteins gelsolin and vitamin-D-binding protein (GC-globulin) (Lee & Galbraith, 1992;Lind et d., 1986). Besides binding actin monomers and severing actin filaments, gelsolin is a potent actin nucleating protein thus favouring polymerization.…”

Section: Discussionmentioning

confidence: 99%

Actin enhances the haemolytic activity of Escherichia coli

et al. 1998

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Actin is a major cytoskeletal protein of mammalian muscle and non-muscle cells. Exposure of cells to soluble factors that damage cell membranes results in the release of actin into the extracellular spaces. The a-haemolysin (HlyA) of Escherichia coli is the prototype RTX (repeat in toxin) toxin and is thought t o be important in virulence because of its ability to lyse cells by formation of pores in the cell membrane. These studies were conducted to determine if actin influences growth and haemolytic activity of E. coli. Growth of E. coli in the presence of actin resulted in culture supernatant haemolytic activity that was 2.4-,27-and 33-fold greater than that of E. coli grown in medium containing BSA, non-supplemented medium, or medium containing heatdenatured actin, respectively. The enhanced haemolytic activity occurred only when actin was present during the growth phase and there was no effect when actin was added to culture Supernatants containing haemolysin. The increased haemolytic activity by actin was concentration-dependent, detectable in early-exponential-phase growth, and associated with increased concentrations of secreted HlyA by Western blotting. Actin induced a 29-fold increase in alkaline phosphatase activity in f. coli CC118 with a TnphoA insertion in the hlyB determinant of the recombinant haemolysin plasmid pWAM04. These results indicate that extracellular actin enhances haemolysin production by Em coli and may have implications in the pathogenesis of E. coli infections.

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Role of plasma gelsolin and the vitamin D-binding protein in clearing actin from the circulation.

Cited by 152 publications

References 35 publications

Gelsolin is Depleted in Post-Shock Mesenteric Lymph

Gelsolin is Depleted in Post-Shock Mesenteric Lymph

Temporal profile of total, bound, and free Gc-globulin after acetaminophen overdose

Actin enhances the haemolytic activity of Escherichia coli

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