Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P02774 (Gc-globulin)
 196 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Gc-globulin scavenges actin liberated from necrotic cells. We measured serum Gc-globulin and the degree of complexing with monomeric actin (complex ratio) in the initial phase of paracetamol (acetaminophen) intoxication and related this to the severity of liver necrosis and the clinical course. In eighteen patients with paracetamol intoxication serial measurements of serum Gc-globulin and complex ratio were determined from admission and every three hours thereafter. Eight patients developed hepatic encephalopathy (HE) and two of them died. On admission all patients had significantly reduced serum Gc-globulin levels compared to normal individuals, and patients with HE had significantly lower values than patients without HE. All patients with HE had at least three samples, where Gc-globulin was below 120 mg/l (35% of normal). Complex ratio on admission did not differ significantly in the patients with and those without HE. The peak complex ratio was higher in patients with HE than in patients without HE, and three of four patients with peak complex ratio above 75% had HE. In conclusion, Gc-globulin levels were found to be decreased in patients with paracetamol intoxication; this decrease correlated with the most severe sign of liver dysfunction, HE. Serum Gc-globulin below 120 mg/l and peak complex ratios above 75% may be critical values.
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PMID:[Gc-globulin in paracetamol poisoning]. 896 27

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.
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PMID:Temporal profile of total, bound, and free Gc-globulin after acetaminophen overdose. 1151 20

This doctoral thesis is based on seven previously published papers and reports on the role of the actin-scavenger Gc-globulin in acute and chronic liver diseases. Gc-globulin is synthesized in the liver and is a multifunctional protein; however, its main physiologic function is presumably actin binding and actin scavenging. Actin is a major cellular protein released during cell necrosis that may cause fatal formation of actin-containing thrombi in the circulation if the actin scavenging capacity of Gc-globulin is exceeded. In my studies, I found serum Gc-globulin levels to be reduced in liver disease, most so in patients with acute liver failure (ALF). In patients admitted with acetaminophen (paracetamol) overdose, Gc-globulin concentrations were lower in patients with hepatic encephalopathy than in those without and the levels nadired at approximately 60-72 hours after acetaminophen ingestion, corresponding with the peak in aminotransferese levels (and thus, hepatic necrosis). In patients with ALF, admission Gc-globulin was significantly lower in 47 nonsurvivors than in 30 survivors, 26% and 46% of normal, respectively (P<0.001). The predictive value of outcome using a Gc-globulin cutoff level of 100 mg/L equaled that of the internationally accepted King's College Hospital criteria. The prognostic value of Gc-globulin was confirmed in a separate study including 106 patients from the United States with nonacetaminophen-induced ALF now using an automated nephelometric assay whereas the prognostic value seemed less obvious for acetaminophen-induced ALF. Multiple organ failure (MOF) is a frequent complication of ALF. In ALF patients with deep coma (hepatic encephalopathy grade III or IV) Gc-globulin levels correlated inversely with the number of failing organs. Levels were lower in patients who later developed MOF than in those who did not. Surprisingly, kinetic studies in patients with ALF and acute on chronic liver disease showed Gc-globulin production to be 7-fold increased in these conditions. Despite this increase Gc-globulin levels were severely reduced and the reduction must therefore be due to a highly increased consumption of Gc-globulin - probably because of hepatocyte necrosis and removal from the circulation of Gc-globulin:actin complexes or because of its role in immune-related functions. Patients with chronic liver disease had reduced Gc-globulin levels, but the reduction was less pronounced than in ALF. After liver transplantation, Gc-globulin concentrations normalized within two weeks, in contrast to the continuous decrease in albumin levels suggesting a very different regulation of these two phylogenetically related proteins. It remains to be studied if lack of Gc-globulin contributes to the pathogenesis of patients with ALF or chronic liver disease. Future studies should focus on the potential value of Gc-globulin substitution in these patients.
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PMID:Gc-globulin in liver disease. 1923 64