Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P04040 (Catalase)
 3,577 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The ability of ethanol and arachidonic acid (AA), as inducers of oxidative stress and key factors in alcoholic liver disease, to up-regulate alpha 2 collagen type I (COL1A2) gene expression was studied in a hepatic stellate cell line overexpressing the ethanol-inducible cytochrome P450 2E1 (CYP2E1) (E5 cells). A time- and dose-dependent induction in COL1A2 mRNA by ethanol or AA was observed that was prevented by diallylsulfide, a CYP2E1 inhibitor. Nuclear run-on experiments showed transcriptional activation of the COL1A2 gene by ethanol and AA. Catalase abrogated the increase in COL1A2 mRNA suggesting an H(2)O(2)-dependent mechanism. Cyclooxygenase-2 (COX-2) levels and production of prostaglandin E(2) upon addition of AA were elevated in the E5 cells. Incubation with NS-398, a COX-2 inhibitor, blocked the effect of AA, but not of ethanol, on COL1A2 expression suggesting that CYP2E1 activates COX-2 expression, and the oxidation of AA by COX-2 is responsible for the increase in COL1A2. Activity of a reporter construct driven by -378 base pairs of the proximal promoter region of the COL1A2 gene increased in E5 but not control cells and was further increased by ethanol or AA. These experiments link CYP2E1-dependent oxidative stress to induction of COX-2 and the actions of ethanol and AA on activation of collagen gene expression in hepatic stellate cells.
 ...
PMID:Ethanol and arachidonic acid increase alpha 2(I) collagen expression in rat hepatic stellate cells overexpressing cytochrome P450 2E1. Role of H2O2 and cyclooxygenase-2. 1077 Sep 28

The human colon carcinoma cell line LIM1215 proliferates and changes morphology (spread) in a cell density-dependent manner in response to epidermal growth factor (EGF). At high density, production of autocrine transforming growth factor-alpha enables the cells to proliferate and spread in the absence of exogenous EGF or serum. At low cell density (< 1 x 10(4)/cm2) EGF alone fails to elicit a mitogenic or morphological response and requires the presence of conditioned medium (derived from high cell density serum-free culture of the same cells) to exert its effects. This synergy between EGF and LIM1215 conditioned medium was investigated further. Using a low cell density assay and fractionated LIM1215 conditioned medium, we show that EGF-mediated mitogenic and morphological responses are separable. These responses are dependent on the synergistic action of a low molecular weight autocrine survival factor and an extracellular matrix-like spreading factor(s) secreted into the culture medium respectively. We find that under low cell density, serum-free conditions, EGF alone is insufficient to rescue LIM1215 from rapid apoptotic death. Catalase or LIM1215 autocrine survival factor prevent the death of LIM1215 cells and restore their proliferative (but not morphological) response to EGF, suggesting that cell death under these conditions may be the result of oxidative stress. Combination of EGF, partially purified autocrine survival and spreading factors induced proliferation and spreading of low density LIM1215 cells similar to that observed with EGF and unfractionated conditioned medium. GRGDS peptides strongly inhibited the spreading of LIM1215 cells in the presence of EGF and the partially purified autocrine spreading factor, demonstrating that integrin receptors are involved in the spreading process. Comparison of the spreading response of LIM1215 and Colo 526 cells on ASF and various adhesion proteins indicate that ASF is not collagen-I, collagen-IV, fibronectin or vitronectin. Taken together, these results support the concept that the autonomous growth of colon carcinoma cells in vitro is dependent on the synergistic interaction between several autocrine systems.
 ...
PMID:Multiple autocrine factors including an extracellular matrix protein are required for the proliferation and spreading of human colon carcinoma cells in vitro. 1083 Oct 71

There are 2 to 6 billion betel quid (BQ) chewers in the world. Areca nut (AN), a BQ component, modulates arachidonic acid (AA) metabolism, which is crucial for platelet function. AN extract (1 and 2 mg/ml) stimulated rabbit platelet aggregation, with induction of thromboxane B2 (TXB2) production. Contrastingly, Piper betle leaf (PBL) extract inhibited AA-, collagen-, and U46619-induced platelet aggregation, and TXB2 and prostaglandin-D2 (PGD2) production. PBL extract also inhibited platelet TXB2 and PGD2 production triggered by thrombin, platelet activating factor (PAF), and adenosine diphosphate (ADP), whereas little effect on platelet aggregation was noted. Moreover, PBL is a scavenger of O2(*-) and *OH, and inhibits xanthine oxidase activity and the (*)OH-induced PUC18 DNA breaks. Deferoxamine, 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA) and neomycin prevented AN-induced platelet aggregation and TXB2 production. Indomethacin, genistein, and PBL extract inhibited only TXB2 production, but not platelet aggregation. Catalase, superoxide dismutase, and dimethylthiourea (DMT) showed little effect on AN-induced platelet aggregation, whereas catalase and DMT inhibited the AN-induced TXB2 production. These results suggest that AN-induced platelet aggregation is associated with iron-mediated reactive oxygen species production, calcium mobilization, phospholipase C activation, and TXB2 production. PBL inhibited platelet aggregation via both its antioxidative effects and effects on TXB2 and PGD2 production. Effects of AN and PBL on platelet aggregation and AA metabolism is crucial for platelet activation in the oral mucosa and cardiovascular system in BQ chewers.
 ...
PMID:Modulation of platelet aggregation by areca nut and betel leaf ingredients: roles of reactive oxygen species and cyclooxygenase. 1197 87

Leptin is recognized as a profibrogenic hormone in the liver, but the mechanisms involved have not been clarified. The tissue inhibitor of metalloproteinase (TIMP)-1, which acts through inhibition of collagen degradation, is synthesized by activated hepatic stellate cells (HSC) in response to fibrogenic substances. The capacity of leptin to induce TIMP-1 and its signaling molecules were investigated in a human HSC cell line, LX-2. Leptin stimulated TIMP-1 protein, mRNA, and promoter activity. JAK1 and -2, as well as STAT3 and -5, were activated. After leptin, there was increased expression of tyrosine 1141-phosphorylated leptin receptor, which may contribute to STAT3 activation. AG 490, a JAK inhibitor, blocked JAK phosphorylation with concomitant inhibition of STAT activation, TIMP-1 mRNA expression, and promoter activity. Leptin also induced an oxidative stress, which was inhibited by AG 490, indicating a JAK mediation process. ERK1/2 MAPK and p38 were activated, which was prevented by catalase, indicating an H2O2-dependent mechanism. Catalase treatment resulted in total suppression of TIMP-1 mRNA expression and promoter activity. SB203580, a p38 inhibitor, prevented p38 activation and reduced TIMP-1 message half-life with down-regulation of TIMP-1 mRNA. These changes were reproduced by overexpression of the dominant negative p38alpha and p38beta mutants. PD098059, an ERK1/2 inhibitor, opposed ERK1/2 activation and TIMP-1 promoter activity, leading to TIMP-1 mRNA down-regulation. Thus, leptin has a direct action on liver fibrogenesis by stimulating TIMP-1 production in activated HSC. This process appears to be mediated by the JAK/STAT pathway via the leptin receptor long form and the H2O2-dependent p38 and ERK1/2 pathways via activated JAK.
 ...
PMID:Leptin stimulates tissue inhibitor of metalloproteinase-1 in human hepatic stellate cells: respective roles of the JAK/STAT and JAK-mediated H2O2-dependant MAPK pathways. 1462 4

Tissue homeostasis is determined by the balance between oxidants and antioxidants. Catalase is an important antioxidant enzyme regulating the level of intracellular hydrogen peroxide and hydroxyl radicals. The effect of catalase deficiency on renal tubulointerstitial injury induced by unilateral ureteral obstruction (UUO) has been studied in homozygous acatalasemic mutant mice (C3H/AnLCs(b)Cs(b)) compared with wild-type mice (C3H/AnLCs(a)Cs(a)). Complete UUO caused interstitial cell infiltration, tubular dilation and atrophy, and interstitial fibrosis with accumulation of type IV collagen in obstructed kidneys (OBK) of both mouse groups. However, the degree of injury showed a significant increase in OBK of acatalasemic mice compared with that of wild-type mice until day 7. The deposition of lipid peroxidation products including 4-hydroxy-2-hexenal, malondialdehyde, and 4-hydroxy-2-nonenal was severer in dilated tubules of acatalasemic OBK. Apoptosis in tubular epithelial cells significantly increased in acatalasemic OBK at day 4. Expression of caspase-9, a marker of mitochondrial pathway-derived apoptosis, increased in dilated tubules of acatalasemic mice. The level of catalase activity remained low in acatalasemic OBK until day 7 without compensatory upregulation of glutathione peroxidase activity. The data indicate that acatalasemia exacerbated oxidation of renal tissue and sensitized tubular epithelial cells to apoptosis in OBK of UUO. This study demonstrates that catalase deficiency enhanced tubulointerstitial injury and fibrosis in a murine model of UUO and thus supports the protective role of catalase in this model.
 ...
PMID:Acatalasemia sensitizes renal tubular epithelial cells to apoptosis and exacerbates renal fibrosis after unilateral ureteral obstruction. 1472 14

Pretreatment with zinc produces tolerance to several cadmium toxic effects. This study was performed to further elucidate the mechanism of zinc-induced tolerance to cadmium cytotoxicity in a rat hepatic stellate cell line (CFSC-2G). Twenty four hours after seeding, cells were treated with 60 micromol/L ZnCl2 for 24 h. Following zinc pretreatment, cells were exposed to 3 micromol/L and 5 micromol/L CdCl2 for an additional 24 h. The toxicity of cadmium was significantly reduced in the zinc-pretreated cells. Zinc pretreatment produced a decrease in lipid peroxidation damage of cadmium-treated cells. Glutathione cell content diminished 33% and 43% as a result of 3 micromol/L and 5 micromol/ L CdCl2 treatment, respectively. Cell pretreatment with zinc recovered glutathione content at control cells level. Catalase and glutathione peroxidase activities were also recovered to control values with zinc pretreatment. Cadmium (5 micromol/L) was able to induce 39% the expression of alpha1 collagen (I) gene after 1 h treatment, while zinc pretreatment prevented this cadmium profibrogenic effect. We also examined the production of heat shock protein 70 (Hsp70) as a cellular response to oxidative stress produced by cadmium. By Western blot analysis, a 1.3 and 3 times increment in Hsp70, with 3 micromol/L and 5 micromol/L CdCl2 treatment, respectively, was observed. Zinc pretreatment prevented the production of Hsp70. Metallothionein-II (MT-II) gene expression was induced by cadmium, but the induction was unaffected with zinc pretreatment. These data suggest that zinc-induced protection against the cytotoxicity of cadmium in stellate cells may be related to the maintenance of normal redox balance inside the cell.
 ...
PMID:Zinc pretreatment prevents hepatic stellate cells from cadmium-produced oxidative damage. 1549 71

The impact of Kupffer cells (KCs) on the hepatic stellate cell (HSC) fibrogenic response was examined in an in vitro coculture model of primary KCs and HSCs. Coculture with KCs induced a more activated phenotype and greater proliferation compared to HSC cultured alone. Similar results were obtained on Matrigel which maintains HSCs quiescent. The effect of KCs on HSC collagen I involved transcriptional regulation, as determined by nuclear in vitro transcription run-on assays, promoter studies, and Northern blot analysis, while stability of the COL1A1 and COL1A2 mRNA were similar. The minimal COL1A1 and COL1A2 promoter regions responsible for the KC effects were localized to the -515 and -378 base pair (bp) regions, respectively. Intracellular and extracellular collagen I protein, H2O2, and IL-6 increased in a time-dependent fashion, especially for HSCs in coculture. Catalase prevented these effects as well as the transactivation of both collagen promoters. The rate of collagen I protein synthesis and intracellular collagen I degradation remained similar but the t(1/2) of the secreted collagen I was lower for HSC in coculture. MMP13, a protease that degrades extracellular collagen I, decreased in the cocultures, while TIMP1, a MMP13 inhibitor, increased; and these effects were prevented by catalase, anti-IL-6, and siRNA-IL-6. Cocultured HSC showed elevated phosphorylation of p38 which when inhibited by catalase, anti-IL-6, and siRNA-IL-6 it blocked TIMP1 upregulation and collagen I accumulation. In conclusion, these results unveil a novel dual mechanism mediated by H2O2 and IL-6 by which KCs may modulate the fibrogenic response in HSCs.
 ...
PMID:Oxidative-stress and IL-6 mediate the fibrogenic effects of [corrected] Kupffer cells on stellate cells. 1713 87

Improvement of O(2) supply in bioartificial liver devices remains a critical issue in maintaining hepatocyte viability and functions. Therefore, the current study investigates whether enhanced oxygen (O(2)) transport through collagen extracellular matrix (ECM) can produce a more stable antioxidant defense in different O(2) tensions during prolonged incubation times. Total glutathione concentration of cultured hepatocytes in enhanced ECM was significantly higher than in normal ECM under the lowest O(2) tension phase (2.60mm of thickness from O(2) source), and was also significantly increased in 0.52 mm transport distance of hypoxia as compared to normoxic conditions. Catalase and glutathione reductase activities for hepatocytes within enhanced ECM were also significantly preserved relative to their values for the normal collagen ECM. Specifically, the enhanced ECM produced higher activities at a further transport distance (1.56 mm) from the O(2) source at the 24 h time-point, and remained higher up to the 96 h incubation time. In contrast, the glutathione peroxidase activities in both collagen ECM systems were similar. Hepatocyte viability in the enhanced ECM system was also consistently greater than that for normal ECM. These results suggest that the O(2) enhanced collagen ECM preserves the antioxidant defense system as compared to normal collagen ECM, ostensibly via increased micropathways for O(2) transport to the hepatocytes.
 ...
PMID:Antioxidant functionality in hepatocytes using the enhanced collagen extracellular matrix under different oxygen tensions. 1751 51

Advanced Glycation End-products (AGE-s) were shown to exhibit a number of potentially harmful properties in contact with cells and tissues. As their concentrations increases with age, faster even in hyperglycemic individuals, they are considered important for aging- and age-associated pathologies, especially for athero-arteriosclerosis and type II diabetes. We describe here the methods used for the demonstration of a direct cytotoxicity of several AGE-products when added to human skin fibroblast cultures. This cytotoxicity was still demonstrable when cells, previously cultured with AGE-s, were transferred to new medium without AGE-s. This effect, the remanence of cytotoxicity in absence of AGE-s, suggests a certain degree of inheritance, possibly by epigenetic mechanisms, of the cytotoxic effect of AGE-s, mediated by the AGE-receptors (RAGE-s) and inhibited by free radical-scavengers, such as L-Carnosine, Catalase and Rhamnose-rich oligo- and polysaccharides. Such cytotoxicity can occur not only on the skin but also in other tissues. It appears thus that besides the crosslinking of collagen and other macromolecules, the products of the Maillard reaction can exert their harmful cytotoxic effects directly on the cells.
 ...
PMID:[Demonstration of the cytotoxic effect of Advanced Glycation Endproducts (AGE-s)]. 1797 52

In this study, the effect of gamma rays has been investigated on the normal rat skin using biomechanical, biochemical and histological techniques. Seventeen male Wistar albino rats were divided into two groups (control (n=7) and irradiated (n=10)). The irradiated group was treated with a (60)Co gamma source at a dose of 10Gy at room temperature. Skin biomechanics were measured with tensile test using biomaterial testing machine and maximum load, stiffness, energy absorption capacity, ultimate stress, ultimate strain and elastic modulus were calculated. In the irradiated group, energy, strain and toughness were significantly lower than in the control group (p<0.05). However, strength, displacement, stiffness, stress and elastic modulus were similar to that of the control group (p>0.05). Catalase (CAT) activities and the levels of malondialdehyde (MDA) in the skin of rats were measured using the biochemical methods. MDA levels significantly increased whereas CAT activities decreased in the irradiated group as compared with the control group (p<0.05). Diameters of collagen fibers were measured by transmission electron microscopy. There was no significant difference (p>0.05) between control and irradiated groups for collagen fiber diameter. Thickness of epidermis was significantly lower than the control group. There were no changes in the epidermis between the irradiated group and the control group ultrastructurally. The results of this study show that the gamma irradiation has a significant effect on normal healthy skin.
 ...
PMID:Exposure to gamma rays induces early alterations in skin in rodents: Mechanical, biochemical and structural responses. 1901 66


<< Previous 1 2 3 Next >>