Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Treatment of isolated mitochondria from rat hepatoma tumor cells (AS-30D) with the oxidant, t-butyl hydroperoxide (tBuOOH, 1 or 5 mumol/ml) resulted in the oxidation of glutathione (GSH to GSSG) and the formation of protein-glutathione mixed disulfides (ProSSG). The GSSG was retained inside of the hepatoma mitochondria. In the presence of ADP+succinate (5 or 10 mM), or ketoglutarate (10 mM) or malate (5 mM), the GSSG was reduced to GSH, but the amount of ProSSG stayed constant. With saline or ADP+glutamate (10 mM)/malate (0.1 mm) no reduction of GSSG to GSH occurred. The presence of antimycin (5 micrograms/ml) with ADP+succinate inhibited reduction. At a concentration of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU, 0.5 mM) which inhibited a major portion of the glutathione reductase activity, the reduction of GSSG to replenish GSH was also inhibited. NADPH may play a critical role as well, for the addition of 2.4 mM NADPH to permeabilized hepatoma mitochondria fostered the reduction of GSSG after tBuOOH treatment. Therefore, hepatoma mitochondria possess a glutathione reductase-dependent system to reduce GSSG to GSH. The reaction only occurs with actively respiring mitochondria.
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PMID:Glutathione disulfide reduction in tumor mitochondria after t-butyl hydroperoxide treatment. 139 20

The importance of some glutathione metabolic pathways was examined in two highly dedifferentiated hepatomas, Yoshida AH-130 and Morris 3924 A hepatomas, and in normal liver in relation to their role against oxidative stress. The cytosol prepared from Yoshida hepatoma cells decreased the peroxidation rate in normal liver microsomes and mitochondria, but this antioxidant property was not displayed by Morris hepatoma. Glutathione peroxidase and glutathione-S-transferases activities were extremely low in both hepatomas; glutathione reductase activity values were about half the normal liver values. The large decrease in glutathione peroxidase and glutathione-S-transferases suggests that in these two tumors only small amounts of GSH can be used in reduction or conjugation reactions, such as the reduction of hydrogen peroxide and lipid hydroperoxides or the conjugation of GSH with the end products of lipoperoxidation, aldehydes or ketones. The hypothesis of a more efficient GSSG reduction in hepatomas, due to the low glutathione peroxidase/glutathione reductase activity ratio, is also discussed. The described changes in glutathione related enzymes do not seem to have any correlation with the protective effect against the lipoperoxidative processes displayed by some tumors since these enzymatic activities were similar in both hepatomas whereas only Yoshida hepatoma showed antioxidant properties.
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PMID:Analysis of glutathione-dependent enzyme activities in two different rat hepatomas and in normal liver in relation to their role in resistance to oxidative stress. 323 5

Exposed thiol groups do not appear to be related to the binding of (32)P-labelled polyribosomes to stripped rough endoplasmic reticulum in vitro. Treating stripped rough endoplasmic reticulum with GSSG did not diminish binding of polyribosomes, suggesting that binding in vitro has no correlation with the inhibition of protein synthesis in vitro reported by Kosower et al. (1971). Thiol reagents, which are known to dissociate ribosomes, did not significantly decrease binding of (32)P-labelled polyribosomes to stripped rough endoplasmic reticulum. Denaturing the protein of (32)P-labelled polyribosomes or stripped rough endoplasmic reticulum of liver or hepatoma with heat, trichloroacetic acid, or HClO(4) did not alter the binding in vitro. Therefore, the practice of measuring the binding of (32)P-labelled polyribosomes to stripped rough endoplasmic reticulum in vitro (Shires et al., 1971b) is an unsuitable indicator of biological significance in the intact cell.
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PMID:Binding of rat liver and hepatoma polyribosomes to stripped rough endoplasmic reticulum in vitro. Biological or an artifact? 434 80

Total homogenates from liver tissues, as well from Morris 3924 A and Yoshida AH-I30 hepatomas display a different degree of thiobarbituric acid reacting substances (TBArs) when incubated "in vitro". It is well known that carbonyl compounds arising from lipoperoxidative decomposition of unsaturated fatty acids can easily react with reduced glutathione (GSH). So, the decay in GSH we have shown in previous experiments could be accounted for GSH trapping by the formed aldehydes. Some discrepancies were, however, seen when the decay in GSH and the increase in GSSG were compared, both in normal and in tumour tissues. It is known that GSH can be destroyed not only through oxidative process, but also through the action of gamma-glutamyl-transpeptidase. In the present paper the decrease of total (TG) and reduced (GSH) glutathione was followed and compared with both the increase in GSSG and the increase in the production of TBArs, during "in vitro" incubation. In normal liver, increase in TBArs production parallels the decay in GSH concentration; GSSG, on the contrary, increases. In AH-I30 Yoshida hepatoma cells, TBArs production is lower and GSSG is also decreased. In 3924 A Morris hepatoma GSH decrease is similar to that observed in the liver, while TBArs production is lower and GSSG is also decreased. Analysis of TG content during the incubation-time suggests that GSH decay in both hepatoma types is essentially due to gamma-glutamyl-transpeptidase action, whilst GSH oxidation to GSSG is decreased.
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PMID:[Differences in glutathione oxidation and transpeptidylation between normal liver and hepatomas (author's transl)]. 612 64

Lipid peroxidation rate in four different hepatomas is quite different and seems to be related to their degree of deviation, low deviation tumours displaying higher peroxidative ability. Moreover, the supernatant of the highly anaplastic Yoshida hepatoma is able to decrease the peroxidation rate in normal liver microsomes. This antioxidant ability is not dependent upon an increased level of glutathione. The concentration of reduced glutathione (GSH) declines strongly during incubation in conditions favouring lipid peroxidation. Unlike normal liver homogenates, this decline of GSH in hepatomas is not due to the transformation of GSH into oxidized glutathione (GSSG) but mostly to the increased activity of the gamma-glutamyl-transpeptidase pathway.
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PMID:Lipid peroxidation in hepatomas of different degrees of deviation. 614 7

Liver glutathione-peroxidase (L-GSH-Px) and glutathione-reductase (GSSG-Red) activities were measured in supernatants of liver tissues obtained from a total of 36 subjects. Sixteen of these patients had a functionally normal liver (control group), whereas of the remaining 20 patients, 10 were cirrhotic and 10 had a liver disease other than cirrhosis. The mean value of L-GSH-Px of the control group was 33.12 +/- 12.66 U/g protein, a value similar to that found in patients with liver disease. The L-GSH-Px of the control group was positively correlated with the age of the subjects (r = 0.620; p less than 0.02). In contrast, in patients with liver disease an opposite behaviour of the two parameters was noted (r = -0.497; p less than 0.05). L-GSH-Px activity tended to be higher in males than in females, whereas the erythrocyte glutathione-peroxidase (E-GSH-Px) of the same patients was higher in females, albeit not significantly. L-GSH-Px and E-GSH-Px were not correlated either in normal or in liver disease. The mean GSSG-Red of the control group was 40.63 +/- 11.10 U/g protein, which is not different from that of the group of liver patients. GSSG-Red was not correlated with L-GSH-Px or with the age of patients. In two patients with hepatoma, the GSH-Px activity of the cancer tissue was low and the GSSG-Red activity high.
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PMID:Glutathione-peroxidase and glutathione-reductase activities of normal and pathologic human liver: relationship with age. 625 11

Low values of pH are known to increase lipid peroxidation during "in vitro" incubation of rat liver homogenates. Non protein sulphydryl compounds decrease more rapidly when the pH of the homogenate is lower. The increase in incubation temperature stimulates the production of TBArs. At high temperature values the -SH groups content of liver tissue falls quickly; the rate of this fall, at the same temperature values, shows differences at different pH. In all experimental conditions the decrease of -SH groups precedes the stimulation of TBArs production and it is mainly due to GSH oxidation, being the decrement of total glutathione very low. Total homogenate from Yoshida AH-130 hepatoma shows no production of GSSG even when incubate for 2 hours at 40 degrees C and at pH 6. The importance of the role played by carbonyl compounds arising from peroxidative decomposition of unsaturated fatty acids on GSH decrement in liver homogenates is discussed and the difference between Yoshida hepatoma and normal liver, as far as GSH decrease is concerned, is discussed.
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PMID:[Kinetics of sulphur compounds decrease in liver homogenates during in vitro incubation in experimental conditions modifying lipid peroxidation rate]. 686 Apr 99

A novel pathway of polycyclic aromatic hydrocarbon (PAH) metabolism involves the oxidation of non-K-region trans-dihydrodiols by dihydrodiol dehydrogenase (DD) to yield PAH o-quinones whose cytotoxicity and genotoxicity are unknown. The cytotoxicity of several PAH o-quinones derived from this reaction [naphthalene-1,2-dione (NPQ), benzo[a]pyrene-7,8-dione (BPQ), and 7,12-dimethylbenz[a]anthracene-3,4-dione (DMBAQ)] was examined in rat (H-4IIe) and human (Hep-G2) hepatoma cells which are known to express DD. 2-Methylnaphthalene-1,4-dione (menadione), a known cytotoxic p-quinone, was used as a positive control. Hepatoma cells (1 x 10(6) cells/mL) were exposed to PAH o-quinones (1-100 microM) for 0-4 h, and cell viability and survival were measured and related to O2.- production and changes in redox potential [GSSG/GSH and NAD(P)+/NAD(P)H]. Three different modes of cytotoxicity were observed: (1) NPQ (no bay region) and DMBAQ (methylated bay region) were as cytotoxic as menadione in reducing cell survival but had less effect on cell viability. These o-quinones adversely affected GSH levels and the redox state of the cell and caused an increase in the production of O2.- in cell suspensions. This cytotoxicity was not enhanced by dicoumarol (10 microM), a DT-diaphorase inhibitor, implying that this enzyme is unable to prevent these PAH o-quinones from entering one-electron redox-cycles. (2) BPQ (bay region only) was the least cytotoxic of the PAH o-quinones studied. BPQ decreased cell viability (< 40% at 20 microM) but did not adversely affect cell survival or the redox state of the cell.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cytotoxicity of polycyclic aromatic hydrocarbon o-quinones in rat and human hepatoma cells. 768 7

A recent study has suggested that degraded adducts smaller than 2 kDa in molecular weight of bovine serum albumin (BSA)-conjugated doxorubicin (DXR) (BSA-DXR) might exhibit cytotoxicity against multidrug resistant (MDR) cells. To investigate this notion further, intracellular accumulation and cytotoxicity of DXR coupled to several small peptides, such as glycylglycine (diGly), glycylglycylglycine (triGly), reduced glutathione (GSH) and oxidized glutathione (GSSG), were investigated using DXR-sensitive (AH66P) and DXR-resistant (AH66DR) rat hepatoma cell lines. Against both AH66P and AH66DR cells, diGly-conjugated DXR (diGly-DXR) and triGly-conjugated DXR (triGly-DXR) demonstrated the same cytotoxic activity as DXR, and the accumulation of both conjugates in the two cell lines was almost similar to that of DXR. After treatment of AH66DR cells with 5 microM verapamil [an inhibitor of P-glycoprotein (Pgp)], the intracellular levels of diGly-DXR and triGly-DXR were markedly increased and consequent cytotoxicity was improved. On the other hand, GSH-conjugated DXR (GSH-DXR) showed 9- and 7.5-fold more cytotoxic activity than BSA-DXR against AH66P and AH66DR cells, respectively. GSH-DXR accumulated rapidly in AH66DR cells, probably by the same mechanism as in AH66P cells, because the treatment of AH66DR cells with verapamil did not cause a significant increase in the intracellular drug level as compared with that in cells treated without verapamil. The levels of cytotoxicity and accumulation of GSSG-DXR were the same as those of BSA-DXR for both cell lines. These results indicate that GSH-DXR exerts potent cytotoxicity against both cell lines among the peptide DXR conjugates examined because of the rapid uptake and high accumulation of GSH-DXR similar to that of DXR without efflux.
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PMID:Drug conjugate of doxorubicin with glutathione is a potent reverser of multidrug resistance in rat hepatoma cells. 907 16

The level of lipid peroxidation products and the content of glutathione in erythrocytes of rats with Morris 5123 hepatoma at different stages of tumor development were examined. The content of endogenous malondialdehyde (MDA) was increased throughout all periods of tumor development as compared to the results for healthy rats. From the extent of MDA generation under oxidative stress we concluded that erythrocytes of Morris 5123 hepatoma bearing rats were more susceptible to autoxidation than those from control rats. The content of reduced glutathione (GSH) and oxidized glutathione (GSSG) was increased at the early stage of tumor growth. At the advanced stage of the disease both the content of GSH and the GSH/GSSG ratio were decreased while the content of GSSG remained at the elevated level.
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PMID:The effect of experimental neoplastic disease on malondialdehyde level and glutathione status in erythrocytes of rats. 958 57


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