Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P17174 (aspartate aminotransferase)
 14,872 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Osteopontin (OPN) plays a pivotal role in various immune responses and inflammatory diseases. OPN is expressed in various granulomatous diseases; however, the cellular and molecular role of OPN in these diseases is not well known. We analyzed the role of OPN in a beta-glucan-induced hepatic granuloma model. First, we found that neither OPN deficiency nor overexpression of OPN affected the number and the size of hepatic granulomas at day 7, indicating that OPN is not involved in the formation of hepatic granulomas at the early stages. Importantly, OPN did not influence the liver tissue damage as defined by alanine aminotransferase and aspartate aminotransferase levels at early stages. Second, OPN deficiency resulted in the reduction of IL-12 and IFN-gamma production at early stages. Third, at late stages, OPN deficiency resulted in a decrease in the number and size of hepatic granulomas, and a reduction of liver tissue injury. This was due to the reduction of the cellular recruitment including macrophages, CD4 T cells and dendritic cells into the liver, and the reduction of tumor necrosis factor (TNF)-alpha production in the liver. In contrast, overexpression of OPN resulted in the persistence of granuloma formation. These data suggest that OPN affects the persistence of hepatic granuloma formation. Our results indicate that OPN up-regulates the production of IL-12 and IFN-gamma within the granulomas at early stages, and OPN has an additional role in the regulation of cellular recruitment and TNF-alpha production at late stages that determine the severity of liver tissue injury.
 ...
PMID:Osteopontin affects the persistence of beta-glucan-induced hepatic granuloma formation and tissue injury through two distinct mechanisms. 1497 21

Ginsan, a polysaccharide isolated from Panax ginseng, has been shown to be a potent immunomodulator, producing a variety of cytokines such as TNF-alpha, IL-1, IL-2, IL-6, IL-12, IFN-gamma and GM-CSF, and stimulating lymphoid cells to proliferate. In the present study, we analyzed some immune functions 1st-5th days after ginsan i.p. injection, including the level of non-protein thiols (NPSH) as antioxidants, heme oxygenase (HO) activity as a marker of oxidative stress, zoxazolamine-induced paralysis time and level of hepatic cytochrome P-450 (CYP450) as indices of drug metabolism system, and activities of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), total bilirubin, and albumin level as indicators of hepatotoxicity. Ginsan in the dose of 100 mg/kg caused marked elevation (1.7 to approximately 2 fold) of HO activity, decrease of total CYP450 level (by 20-34%), and prolongation of zoxazolamine-induced paralysis time (by 65-70%), and showed some differences between male and female mice. Ginsan treatment did not seem to cause hepatic injury, since serum AST, ALT, and ALP activities and levels of total bilirubin and albumin were not changed.
 ...
PMID:Effects of polysaccharide ginsan from Panax ginseng on liver function. 1520 59

Concanavalin A (ConA) induces natural killer T (NKT) cell-mediated liver damage. Glucocerebroside (GC) is a naturally occurring glycolipid. Our aims were to determine the effect of GC in a murine model of ConA-induced hepatitis. Mice in groups A and B were treated with GC 2 h before and 2 h following administration of ConA, respectively; group C mice were treated with ConA; group D mice was treated with GC; group E mice did not receive any treatment. Liver damage was evaluated by serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels and liver histology. The immune effect of GC was determined by fluorescence-activated cell sorter analysis of intrahepatic and intrasplenic NKT lymphocytes, measurement of cytokine levels, and Western blot analysis for STAT 1, 4, 6, and NF-kappaB expression. The effect of GC on NKT cell proliferation was assessed in vitro. Serum AST and ALT levels were markedly reduced in GC-treated group A mice compared with nontreated group C animals, and histological damage was markedly attenuated in group A. The beneficial effect of GC was associated with a 20% decrease of intrahepatic NKT lymphocytes, significant lowering of serum IFN-gamma levels, and decreased STAT1 and STAT6 expression. In vitro administration of GC led to a 42% decrease of NKT cell proliferation in the presence of dendritic cells but not in their absence. Intraperitoneally administered radioactive GC was detected in the liver and bowel. Administration of GC led to amelioration of ConA hepatitis associated with an inhibitory effect on NKT lymphocytes. GC holds promise as a new immune-modulatory agent.
 ...
PMID:Glucocerebroside treatment ameliorates ConA hepatitis by inhibition of NKT lymphocytes. 1597 88

Group A streptococcus (GAS) infection can cause severe invasive diseases, including necrotizing fasciitis and streptococcal toxic shock syndrome. Cordyceps sinensis, a Chinese herbal medicine, is an immunomodulator. In this study the air-pouch bacterial inoculation model was used to investigate the protective efficacy of C. sinensis mycelium extract against GAS infection. Force-feeding mice with C. sinensis mycelium extract for 3 consecutive days before GAS infection increased the survival rate and reduced local skin-tissue injury compared with mice fed PBS. Bacterial numbers in the air pouch exudates from C. sinensis-treated mice were lower than those from PBS-treated mice. Blood and organs in PBS-treated mice showed bacterial dissemination, but those in C. sinensis-treated mice did not. Three days of pretreatment with C. sinensis extract followed by C. sinensis treatment every other day after GAS infection resulted in 100% survival. The post-GAS-infection levels of aspartate aminotransferase, alanine aminotransferase and blood urea nitrogen in the sera of C. sinensis-treated mice were lower than those of PBS-treated mice. Taken together, these results show that C. sinensis mycelium extract protects by decreasing bacterial growth and dissemination, thereby increasing mouse survival rate. IL-12 and IFN-gamma expression and macrophage phagocytic activity also increased after C. sinensis treatment.
 ...
PMID:Cordyceps sinensis mycelium protects mice from group A streptococcal infection. 1601 34

Fumonisin (FB1), a mycotoxin, is produced by Fusarium moniliforme and F. proliferatum. A prevalence survey in Taiwan by our laboratory showed that there was a contamination rate of 40% in domestic animal feeds, and the average contaminated level was 4.5 mg/kg. Ninety-six birds were allotted into four treatments fed with diets containing 0 (control), 5, 10, or 15 mg/kg of FB1 for three weeks. The results showed that the growth performance was not influenced by the FB1 challenge, but relative bursa weight was significantly decreased. The activity of serum aspartate aminotransferase, and the serum levels of albumin and cholesterol were significantly elevated by the FB1 challenges. When broilers were stimulated with injection of lipopolysaccharides, mRNA abundance (determined by semi-quantitative RT-PCR) interleukin-1beta (IL-1beta), IL-2, interferon-alpha (IFN-alpha), IFN-gamma, and inducible nitric oxide synthase (iNOS) reached a plateau at 3 h, and declined at 6 h. A FB1 challenge for three weeks increased cytokine mRNA abundance in broilers. The results also showed that 15 mg FB1 per kg feed significantly inhibited the expression of IL-1beta, IL-2, IFN-alpha, IFN-gamma, but had no effect on iNOS. The macrophage functional profile was significantly changed under an exposure of 15 mg FB1 per kg for three weeks. Taken together, our results suggest that FB1 up to 15 mg/kg does not affect growth performance, but impairs some parameters of blood biochemistry and the immunocompetence in broilers.
 ...
PMID:Effect of fumonisins on macrophage immune functions and gene expression of cytokines in broilers. 1692 24

The results of administering escalating, i.v. doses of targeted nanoparticles containing a siRNA targeting the M2 subunit of ribonucleotide reductase to non-human primates are reported. The nanoparticles consist of a synthetic delivery system that uses a linear, cyclodextrin-containing polycation, transferrin (Tf) protein targeting ligand, and siRNA. When administered to cynomolgus monkeys at doses of 3 and 9 mg siRNA/kg, the nanoparticles are well tolerated. At 27 mg siRNA/kg, elevated levels of blood urea nitrogen and creatinine are observed that are indicative of kidney toxicity. Mild elevations in alanine amino transferase and aspartate transaminase at this dose level indicate that the liver is also affected to some extent. Analysis of complement factors does not reveal any changes that are clearly attributable to dosing with the nanoparticle formulation. Detection of increased IL-6 levels in all animals at 27 mg siRNA/kg and increased IFN-gamma in one animal indicate that this high dose level produces a mild immune response. Overall, no clinical signs of toxicity clearly attributable to treatment are observed. The multiple administrations spanning a period of 17-18 days enable assessment of antibody formation against the human Tf component of the formulation. Low titers of anti-Tf antibodies are detected, but this response is not associated with any manifestations of a hypersensitivity reaction upon readministration of the targeted nanoparticle. Taken together, the data presented show that multiple, systemic doses of targeted nanoparticles containing nonchemically modified siRNA can safely be administered to non-human primates.
 ...
PMID:Administration in non-human primates of escalating intravenous doses of targeted nanoparticles containing ribonucleotide reductase subunit M2 siRNA. 1737 63

Hepatitis B virus (HBV) transgenic mice that express HBV envelope proteins represent a model of chronic HBV infection suitable for the development of therapeutic immunization strategies. To address immunologically therapeutic effects induced by peptide-pulsed DCs, HBV transgenic mice were immunized with peptide-pulsed DCs, and the mice were killed after three times of immunization and the splenocytes were stimulated in vitro and detected by IFN-gamma ELISPOT and cytotoxic T lymphocyte (CTL) activity. The data demonstrated that HBV-specific CD8+ T cell response could be induced and CD8+ T cells had specific CTL activity. Furthermore, ELISA and fluorescent quantitative PCR were performed to detect the level of serum HBsAg and HBV DNA and the results demonstrated that HBV-specific peptide-pulsed DCs could significantly reduce the concentration of serum HBsAg and HBV DNA. The serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities were measured and no significant differences were observed between the different groups, which indicated that no hepatocellular injury occurred. Taken together, the data strongly demonstrated that CD8+ T cell responses and antiviral immunity were elicited in HBV transgenic mice, suggesting that peptide-pulsed DCs could elicit an effective antiviral immunity.
 ...
PMID:Therapeutic potential of dendritic cell-based immunization against HBV in transgenic mice. 1789 31

This study was to investigate the effects of the combination of deoxynivalenol (DON) and zearalenone (ZON) on pigs. Twenty-four weaning piglets were divided into a control group fed a diet free of mycotoxins and a toxin group fed a diet containing 1 mg/kg DON and 250 microg/kg ZON. The results showed that supplementation of DON and ZON in diets had extensive effects on pigs. More specifically, DON and ZON caused levels of total protein, albumin, and globulin in sera to decrease (p < 0.05) by 14.5%, 6.5% and 11.3%, respectively, and at the same time increased (p < 0.05) the serum enzyme activities of gamma-glutamyltransferase, aspartate aminotransferase and alanine aminotransferase by 72.0%, 32.6% and 36.6%, respectively. In addition, DON and ZON decreased (p < 0.05) the level of anticlassical swine fever antibody titers by 14.8%. Real-time PCR showed that DON and ZON caused the mRNA expression levels of IFN-gamma, TNF-alpha, IL-2, to decrease (p < 0.05) by 36.0%, 29.0% and 35.4%, respectively. Histopathological studies demonstrated that DON and ZON caused abnormalities in the liver, spleen, lymph nodes, uterus, and kidney. The concentrations of DON and ZON used in this study are in line with the published critical values permitted by BML. Our study clearly put the standard and adequacy of safety measures for these toxins into question. The authors suggest that with the increasing availability of cellular and molecular technologies, it is time to revisit the safety standards for toxins in feeds so as to make feeds safer, providing consumers with safer products.
 ...
PMID:The combination of deoxynivalenol and zearalenone at permitted feed concentrations causes serious physiological effects in young pigs. 1829 87

To determine the immunological role played by interleukin (IL)-12 family members in Trypanosoma congolense infection, IL-12p35(-/-), IL-12p40(-/-), and IL-12p35(-/-)/p40(-/-) mice were used. While the latter 2 strains lack all IL-12 homologues, IL-12p35(-/-) mice still produce IL-12p80 homodimers and IL-23. Compared with wild-type mice, all infected IL-12-deficient mouse strains showed prolonged survival, whereas parasitemia levels were unaltered. Interferon (IFN)-gamma production in IL-12-deficient mice was strikingly reduced during the acute and chronic stages of infection, coinciding with significantly reduced chronic-stage hepatocellular damage, as demonstrated by histological analysis and plasma aspartate transaminase measurements. In contrast, IL-10 production was not affected by the absence of IL-12. Taken together, these results show that, during T. congolense infection, the absence of IL-12, but not the IL-12p80 homodimer or IL-23, leads to a reduction in IFN-gamma production, which reduces hepatic pathology and improves host survival in conjunction with IL-10 without negatively affecting parasitemia control.
 ...
PMID:Interleukin-12p70 deficiency increases survival and diminishes pathology in Trypanosoma congolense infection. 1881 89

Fulminant inflammation in the liver is often accompanied by the accumulation of IFN-gamma-producing T cells. The BALB/c-Tgfb1(-/-) mouse exhibits extensive, spontaneously developing necroinflammation in the liver, accompanied by the accumulation of IFN-gamma-producing CD4(+) and CD8(+) T cells. Liver damage depends on the presence of an intact Ifng gene. We determined the relevant cellular source(s) of IFN-gamma. In Tgfb1(-/-) liver, CD4(+) T cells were more numerous than CD8(+) T cells and NK cells, and produced more IFN-gamma. Depletion of CD4(+) T cells eliminated both the elevation in plasma IFN-gamma and aspartate aminotransferase, whereas depletion of CD8(+) T cells did not. Rag1(-/-)Tgfb1(-/-) mice exhibited neither IFN-gamma elevation nor tissue damage, indicating that NK cells are not sufficient. IFN-gamma was required for strong overexpression of class II genes but not for CD4(+) T cell activation, oligoclonal expansion, or accumulation in the liver. The T cell inhibitory molecule PD-L1 was strongly expressed in Tgfb1(-/-) livers, ruling out a lack of PD-L1 expression as an explanation for aberrant liver T cell activation. Finally, whereas Tgfb1(-/-) CD4(+) T cells overexpressed Fas ligand, hepatocellular damage was observed in Fas(lpr/lpr)Tgfb1(-/-) mice, indicating that liver pathology is Fas independent. We conclude that liver damage in this model of fulminant autoimmune hepatitis is driven by CD4(+) T cell production of IFN-gamma, is independent of both CD8(+) T cells and the Fas ligand/Fas pathway, and is not explained by a lack of PD-L1 expression.
 ...
PMID:End-organ damage in a mouse model of fulminant liver inflammation requires CD4+ T cell production of IFN-gamma but is independent of Fas. 1923 26


<< Previous 1 2 3 Next >>