Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nitric oxide (NO) has been implicated in playing a role in liver cirrhosis, but the regulatory mechanisms are still unclear. As arginase shares a common substrate with NO synthase (NOS), the aim of this study was to investigate the expression of arginase I and II in cirrhotic liver. Liver cirrhosis was induced in rats by chronic bile duct ligation (BDL). Controls were sham-operated. Competitive polymerase chain reaction was performed to assay the expression of messenger RNA of arginase I and II. Protein expression was detected by immunohistochemistry and western-blotting. The level of arginine in plasma was lower in BDL rats, while the ornithine level in plasma was correspondingly higher (r= -0.96, P<0.0001). Arginase I messenger RNA was reduced significantly in BDL rats (3.34+/-0.32 vs. 1.32+/-0.21 x 10(4) attomole/microg of total RNA, sham vs. BDL, P<0.001), as well as arginase I protein. In contrast, arginase II mRNA was induced in the livers of BDL rats, with negligible expression in controls (0.35+/-0.11 vs. 3.64+/-0.54 attomole/microg of total RNA, sham vs. BDL, P<0.001). Arginase II protein was localized in some hepatocytes and hyperplastic bile ductular epithelial cells of cirrhotic livers but not in control livers. In conclusion, arginase II was induced in BDL livers, while the expression of arginase I was down-regulated. These data suggest that arginase I and II are regulated differently and may have different functions in the livers of BDL rats. Reduction of arginase I in BDL livers may be responsible for the lowering of arginine levels in the plasma, while induction of arginase II could be important in regulating NO synthesis as well as other important mechanisms involved in liver cirrhosis.
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PMID:Induction of arginase II in livers of bile duct-ligated rats. 1193 36

Type II citrullinemia (CTLN2) is characterized by a deficiency of argininosuccinate synthetase (ASS) in the liver. Mutation analysis of the SLC25A13 gene, which is responsible for CTLN2, provides a rapid and accurate diagnosis. We describe clinical, biochemical and histologic features of two patients, whose diagnosis was finally made by mutation analysis. They initially presented with symptoms related to hyperammonemia at 16 to 22 years of age. A patient had shown mental retardation and growth failure from early childhood. Laboratory findings including amino acids, were characteristic, such as elevated citrulline, arginine, and lysine concentrations, but definitive diagnosis had not been made. The patients died of liver cirrhosis and hepatoma at 31 and 34 years old, respectively. Fatty change in the hepatocytes was commonly observed in the autopsied specimens. ASS activity was decreased in the liver of both patients, and a concomitant decrease of arginase activity was found in one case. Investigation for the SLC25A13 mutation revealed that one patient was homozygous for IVS11 + 1G>A, and the other was compound heterozygote (851del4/S225X). Comparison of genetic, enzymatic and biochemical data among various cases of CTLN2 will be essential to understand the real nature of the disease.
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PMID:Application of mutation analysis for the previously uncertain cases of adult-onset type II citrullinemia (CTLN2) and their clinical profiles. 1251 93

Urea cycle disorders (UCD) are human conditions caused by the dysregulation of nitrogen transfer from ammonia nitrogen into urea. The biochemistry and the genetics of these disorders were well elucidated. Earlier diagnosis and improved treatments led to an emerging, longer-lived cohort of patients. The natural history of some of these disorders began to point to pathophysiological processes that may be unrelated to the primary cause of acute morbidity and mortality, i.e., hyperammonemia. Carbamyl phosphate synthetase I single nucleotide polymorphisms may be associated with altered vascular resistance that becomes clinically relevant when specific environmental stressors are present. Patients with argininosuccinic aciduria due to a deficiency of argininosuccinic acid lyase are uniquely prone to chronic hepatitis, potentially leading to cirrhosis. Moreover, our recent observations suggest that there may be an increased prevalence of essential hypertension. In contrast, hyperargininemia found in patients with arginase 1 deficiency is associated with pyramidal tract findings and spasticity, without significant hyperammonemia. An intriguing potential pathophysiological link is the dysregulation of intracellular arginine availability and its potential effect on nitric oxide (NO) metabolism. By combining detailed natural history studies with the development of tissue-specific null mouse models for urea cycle enzymes and measurement of nitrogen flux through the cycle to urea and NO in UCD patients, we may begin to dissect the contribution of different sources of arginine to NO production and the consequences on both rare genetic and common multifactorial diseases.
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PMID:Clinical consequences of urea cycle enzyme deficiencies and potential links to arginine and nitric oxide metabolism. 1546 84

Chronic infection with hepatitis C virus (HCV) is known to be a risk factor for not only cirrhosis and steatosis but also hepatocellular carcinoma (HCC). A number of diagnostic and prognostic molecular markers are being identified by transcriptomic and proteomic analysis of HCC today. However, the analyses are performed on HCC in general, and the studied tissues are HCV infected, HBV infected, infected with both or neither, or the infection status may be unknown. The authors performed proteomic analysis of cancerous and noncancerous tissues from HCC patients with HCV infection, and determined that, in the cancerous tissues, HSP70 family proteins such as GRP78, HSC70, GRP75 and HSP70.1, glutaine synthetase isoforms, HSP60, alpha-enolase, phosphoglycerate mutase 1, ATP synthetase beta chain and triosephosphate isomerase were increased whereas albumin, ferritin light chain, smoothelin, tropomyosin beta chain, arginase 1, aldolase B and kietohexokinase were decreased. The aim of this study is to understand the pathogenesis of HCV-HCC using proteomic analysis of samples from HCV-HCC patients on which transcriptomics has already been performed.
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PMID:Current progress in proteomic study of hepatitis C virus-related human hepatocellular carcinoma. 1609 91

The incidence of hepatocellular carcinoma (HCC) varies widely worldwide. Chronic infection with hepatitis B virus (HBV) and exposure to aflatoxins in foodstuffs are the main risk factors. AAG to AGT transversion at codon 249 of the P53 gene arg-ser (249ser) has been identified as a hotspot, reflecting DNA damage caused by aflatoxin B1 metabolites in HCC. Because HBV infection is often endemic in high aflatoxin exposure areas, it is still not clear whether HBV acts as a con-founder or as a synergistic partner in the development of the 249ser P53 mutation. Serum levels of soluble interleukin 2 receptor (sIL-2R) correlated with the progression of liver cirrhosis independently of its etiology. This fact may reflect the stimulation of T-lymphocytes, monocytes and macrophages in liver cirrhosis. The inter-relationship among aflatoxin exposure, HBV & HCV infections, P53 & sIL-2R in patients with liver cirrhosis and hepatocellular carcinoma was studied. The results revealed significant increase in serum levels of mutant P53, sIL-2R and aflatoxin B1 in patients with cirrhosis and those with HCC compared to the controls. HCC patients showed levels of all the three parameters significantly higher than both cirrhotics and controls (P<0.001). Correlations were found between serum aflatoxin B1, mutant P53 and sIL-2R in HCC group. The results were discussed.
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PMID:Clinical significance of aflatoxin, mutant P53 gene and sIL-2 receptor in liver cirrhosis and hepatocellular carcinoma. 1660 12

Preoperative and postoperative arginase activity was determined in blood serum of 25 patients with liver cirrhosis and 25 patients with hepatocellular carcinoma. The rise of serum arginase activity was observed in the majority of patients before the surgery and the decrease after tumor resection or liver transplantation. The preoperative values of serum arginase activity were similar in both groups of patients. A presence of additional, anionic arginase isoform (All) was demonstrated in serum of studied patients, which was absent in healthy subjects. Thus, our results indicate that the arginase activity cannot differentiate liver cirrhosis and hepatocellular carcinoma. However, arginase isoform All seems to be specific for studied liver diseases.
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PMID:[Serum arginase activity in patients with liver cirrhosis and hepatocellular carcinoma]. 1796 82

Hepatocellular carcinoma (HCC) is one of the most common tumors worldwide affecting preferentially patients with liver cirrhosis. The studies were performed on tissues obtained during surgery from 50 patients with HCC, 40 with liver cirrhosis and 40 control livers. It was found that arginase activity in HCC was nearly 5- and 15-fold lower than in cirrhotic and normal livers, respectively. Isoenzymes AI (so-called liver-type arginase) and AII (extrahepatic arginase) were identified by Western blotting in all studied tissues, however the amount of AI, as well as the expression of AI-mRNA were lower in HCC, in comparison with normal liver, and those of AII were significantly higher. Since HCC is arginine-dependent, and arginine is essential for cells growth, the decrease of AI may preserve this amino acid within tumor cells. Concurrently, the rise of AII can increase the level of polyamines, compounds crucial for cells proliferation. Thus, both arginase isoenzymes seem to participate in liver cancerogenesis.
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PMID:Changes in arginase isoenzymes pattern in human hepatocellular carcinoma. 1883 62

Cirrhosis leads to an inability of the liver to perform its biochemical functions. It can also lead to hepatocellular carcinoma in which, as we showed lately, arginase isoenzyme pattern changes. The present work presents our results on arginase isoenzymes and their possible role in liver cirrhosis. The study was performed on tissues obtained during liver transplantation from 60 patients with liver cirrhosis, and on samples of histologically normal liver (control) from 40 patients with benign or colorectal cancer liver metastases removed during surgery, 6-7 cm from the tumor border. Arginase isoenzymes AI (so-called liver-type arginase) and AII (called extrahepatic arginase) were identified by Western blotting and isolated by ion-exchange chromatography. Their expression on mRNA level was studied by RT-PCR. A significant decrease in arginase activity, dependent of the liver clinical stage, was observed in cirrhotic tissue. Arginase AI activity and its mRNA level were significantly decreased in cirrhotic liver, whereas the activity and expression of arginase AII were concurrently raised, as compared to normal liver. Since arginase AI is a key enzyme of the urea cycle, whereas arginase AII most probably takes part in the biosynthesis of ornithine and polyamines, the defective ammonia inactivation and increased collagen biosynthesis observed in cirrhotic liver may be related to the changes in arginase AI and AII levels, respectively.
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PMID:Arginase isoenzymes in human cirrhotic liver. 1963 40

Chronic hepatitis B (CHB) appears to progress more rapidly in males than in females, and CHB-related hepatic cirrhosis and hepatocellular carcinoma are predominately diseases that tend to occur in men and postmenopausal women. To obtain more insight into the underlying mechanisms of gender disparity of CHB progress, two-dimensional difference gel electrophoresis was employed to compare liver proteome of C57BL/6 and HBV transgenic (HBV-Tg) mice both in male and female groups. We identified 8 differently expressed proteins in male HBV-Tg mice and 12 in female HBV-Tg mice. Apolipoprotein A-I (Apo A-I) was found to be down-regulated in male and female HBV-Tg mouse liver. It is more interesting that the pattern of liver Apo A-I isoforms was altered in male HBV-Tg mice but not in female HBV-Tg mice. Our further results indicated that the basic Apo A-I isoform, based on pI positions from serum 2-dimensional Western blotting, increased in male CHB patient sera but not in female CHB patient sera. Finally, we identified that the oxidative modification Apo A-I mainly reside in basic isoform. This pattern of selectively modified Apo A-I isoforms may be considered as a pathological hallmark that may extend our knowledge of the molecular pathogenesis of CHB progression.
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PMID:An altered pattern of liver apolipoprotein A-I isoforms is implicated in male chronic hepatitis B progression. 1978 85

Over-expression of nitric oxide synthase (NOS) and nitric oxide (NO) formation are associated with the pathogenesis of liver cirrhosis. NO-related stress alters the functions of biomolecules, especially proteins, probably as a result of nitration. The aim of this study was to assess the level of protein nitration and its correlation with the severity of the disease. Liver cirrhosis patients with different grades of severity (grades A, B, and C according to the Child-Pugh classification) were enrolled in this study. Nitroprotein content, arginine, citrulline, NO in terms of total nitrite, nitrosothiol (RSNO) and protein carbonyls were measured in blood. Immunohistochemical detection of nitroprotein was carried out in liver sections of cirrhosis patients. A significant elevation in the levels of serum and platelet arginine, arginase, citrulline, plasma, and platelet nitroproteins, RSNO, total nitrite, protein carbonyls and also a significant amount of nitrated proteins by immunohistochemical detection in tissue were observed in cirrhosis patients. The alterations were highly significant in grade C patients with bleeding complications when compared to those of grade B and A patients. In platelets, both cytosolic and cytoskeletal proteins were found to be nitrated significantly. The level of nitrite seems to have positive correlation with the level of nitroproteins in different grades of cirrhosis. The level of nitroproteins in plasma, platelets and liver tissue can be correlated with the severity of liver cirrhosis.
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PMID:Level of nitrated proteins in the plasma, platelets and liver of patients with liver cirrhosis. 2000 11


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