• Title/Summary/Keyword: glutathione transferase

Search Result 884, Processing Time 0.027 seconds

Anti-inflammatory functions of purpurogallin in LPS-activated human endothelial cells

  • Kim, Tae-Hoon;Ku, Sae-Kwang;Lee, In-Chul;Bae, Jong-Sup
    • BMB Reports
    • /
    • v.45 no.3
    • /
    • pp.200-205
    • /
    • 2012
  • Enzymatic oxidation of commercially available pyrogallol was efficiently transformed to an oxidative product, purpurogallin. Purpurogallin plays an important role in inhibiting glutathione S-transferase, xanthine oxidase, catechol O-methyltransferase activities and is effective in the cell protection of several cell types. However, the anti-inflammatory functions of purpurogallin are not well studied. Here, we determined the effects of purpurogallin on lipopolysaccharide (LPS)-mediated proinflammatory responses. The results showed that purpurogallin inhibited LPS-mediated barrier hyper-permeability, monocyte adhesion and migration and such inhibitory effects were significantly correlated with the inhibitory functions of purpurogallin on LPS-mediated cell adhesion molecules (vascular cell adhesion molecules, intracellular cell adhesion molecule, E-selectin). Furthermore, LPS-mediated nuclear factor-${\kappa}B$ (NF-${\kappa}B$) and tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) releases from HUVECs were inhibited by purpurogallin. Given these results, purpurogallin showed its anti-inflammatory activities and could be a candidate as a therapeutic agent for various systemic inflammatory diseases.

Role of Integrin-Linked Kinase in Multi-drug Resistance of Human Gastric Carcinoma SGC7901/DDP Cells

  • Song, Wei;Jiang, Rui;Zhao, Chun-Ming
    • Asian Pacific Journal of Cancer Prevention
    • /
    • v.13 no.11
    • /
    • pp.5619-5625
    • /
    • 2012
  • Gastric carcinoma is a leading cause of cancer death in the world and multi-drug resistance (MDR) is an essential aspect of gastric carcinoma chemotherapy failure. Recent studies have shown that integrin-linked kinase (ILK) is involved in metastasis of human tumors, expression silencing of ILK inhibiting the metastasis of several types of cultured human cancer cells. However, the role and potential mechanism of ILK to reverse the multi-drug resistance in human gastric carcinoma is not fully clear. In this report, we focused on roles of expression silencing of ILK in multi-drug resistance reversal of human gastric carcinoma SGC7901/DDP cells, including increased drug sensitivity to cisplatin, cell apoptosis rates, and intracellular accumulation of Rhodamine-123, and decreased mRNA and protein expression of multi-drug resistance gene (MDR1), multi-drug resistance-associated protein (MRP1), excision repair cross-complementing gene 1 (ERCC1), glutathione S-transferase -${\pi}$ (GST-${\pi}$) and RhoE, and transcriptional activation of AP-1 and NF-${\kappa}B$ in ILK silenced SGC7901/DDP cells. We also found that there was a decreased level of p-Akt and p-ERK. The results indicated that ILK might be used as a potential therapeutic strategy to combat multi-drug resistance through blocking PI3K-Akt and MAPK-ERK pathways in human gastric carcinoma.

Glutathione S-transferase P1 and DNA Polymorphisms with the Response to Chemotherapy and the Prognosis of Bone Tumor

  • Yang, Li-Min;Li, Xiu-Hua;Bao, Cui-Fen
    • Asian Pacific Journal of Cancer Prevention
    • /
    • v.13 no.11
    • /
    • pp.5883-5886
    • /
    • 2012
  • Osteosarcoma is the most common primary bone malignancy in children and adolescents, and its clinical outcome is poor. We evaluated the response of GSTP1, ERCC1 and ERCC2 to chemotherapy among osteosarcoma patients, and the role of these genes on the prognosis of osteosarcoma. 187 patients with osteosarcoma were administered with methotrexate, cisplatin/adriamycin, actinomycin D, cyclophosphamide, or vincristine treatment. GSTP1, ERCC1 and ERCC2 polymorphism was genotyped by PCR-RFLP assay. The results showed the average survival time of 187 patients were 38.4 months. 97 patients showed response to neoadjuvant chemotherapy. The GSTP1 Val and ERCC2 A/A genotypes had significantly higher rates of response to chemotherapy, with adjusted OR (95% CI) of 2.19 (1.15-6.21) and 2.88 (1.14-13.25). Individuals with ERCC2 A/A genotype were likely to have a lower risk of death from oseosarcoma, and the adjusted HR was 0.32 (0.13-0.95). Our study indicated test of GSTP1 and ERCC2 Lys751Gln polymorphisms might be a candidate pharmacogenomic factors to be explored in the future to identify the osteosarcoma patients who might benefit from chemotherapy.

Inhibitory Effects of Opuntia humifusa on 7, 12-Dimethyl-benz[a]anthracene and 12-O-tetradecanoylphorbol-13-acetate Induced Two-stage Skin Carcinogenesis

  • Lee, Jin-A;Jung, Bock-Gie;Lee, Bong-Joo
    • Asian Pacific Journal of Cancer Prevention
    • /
    • v.13 no.9
    • /
    • pp.4655-4660
    • /
    • 2012
  • Opuntia humifusa, member of the Cactaceae family, was previously demonstrated to have radical scavenging, anti-inflammatory and anti-proliferative effects in in vitro models. It was suggested that O. humifusa could function in the prevention of carcinogenesis. To investigate the in vivo chemopreventive effect of O. humifusa, mice were fed a diet containing either 1% or 3% following 7, 12-dimethylbenz[a] anthracene (DMBA) and 12-O-tetradecanoylphorbol-13-acetate (TPA) induction of skin carcinogenesis. Significant decrease in the numbers of papilloma and epidermal hyperplasia were observed in mice fed with O. humifusa, compared to the control group. O. humifusa also upregulated high total antioxidant capacity and level of phase II detoxifying enzyme such as superoxide dismutase and glutathione S-transferase activity in the skin. Lipid peroxidation activity level was measured in skin cytosol and significantly inhibited in 3% OH fed group compared to the control group. These results suggest that O. humifusa exerts chemopreventive effects on chemical carcinogenesis in mouse skin and that prevention effects are associated with reduction of oxidative stress via the modulation of cutaneous lipid peroxidation, enhancing of total antioxidant capacity especially in phase II detoxifying enzyme system and partial apoptotic influence.

Systematic Analysis on the GSTM1 Null Phenotype and Prostate Cancer Risk in Chinese People

  • Shi, Jing;Zhuang, Yan;Liu, Yan;Yan, Cheng-Quan;Liu, Xian-Kui;Zhang, Ying
    • Asian Pacific Journal of Cancer Prevention
    • /
    • v.16 no.5
    • /
    • pp.2009-2011
    • /
    • 2015
  • Objective: Glutathione S-transferase M 1 (GSTM1) is implicated as a risk factor for prostate cancer. However, this issue is not clear in Chinese population. This systemic analysis was conducted to evaluate the effect of GSTM1 null genotypes on prostate cancer risk in Chinese. Methods: Published studies investigating the associations between GSTM1 null genotypes and the risk of prostate cancer in China were identified by using a predefined search strategy. Main statisticals were pooled and estimated according to the primarily reported data. Results: The prevalence of the GSTM1 null genotype was higher in prostate cancer patients than in controls, with significance. Conclusion: The GSTM1 null genotypes is associated with increased risk of prostate cancer in Chinese.

Molecular characterization and functional analysis of a protease-related protein in Chang-liver cells

  • Wang, Congrui;Zhang, Huiyong;Feng, Huigen;Yang, Baosheng;Pramanik, Jogenananda;Guo, Zhikun;Lin, Juntang
    • BMB Reports
    • /
    • v.43 no.5
    • /
    • pp.375-381
    • /
    • 2010
  • In this study, the cDNA library of Chang-liver cells was immunoscreened using common ADAMs antibody to obtain ADAM related genes. We found one positive clone that was confirmed as a new gene by Blast, which is an uncharacterized helical and coil protein and processes protease activity, and named protease-related protein 1 (ARP1). The submitted GenBank accession number is AY078070. Molecular characterizations of ARP1 were analyzed with appropriate bioinformatics software. To analyse its expression and function, ARP1 was subcloned into glutathione S-transferase fusion plasmid pGEX-2T and expressed by E. coli system. The in vitro expression product of ARP1 was recognized by common ADAMs antibody with western blot. Interestingly, ARP1 cleaves gelatine at pH9.5, which suggests it is an alkaline protease. Semi-quantitative RT-PCR result indicates that ARP1 mRNA is strongly transcribed in the liver and the treated Chang-liver cells.

Molecular Parameters for Assessing Marine Biotoxicity: Gene Expressions of Rockfish (Sebastes schlegeli) Exposed to Polycyclic Aromatic Hydrocarbons

  • Woo, Seon-Ock;Yum, Seung-Shic;Park, Hong-Seog;Jung, Jee-Hyun;Lee, Suk-Chan;Kim, So-Jung;Lee, Taek-Kyun
    • Molecular & Cellular Toxicology
    • /
    • v.3 no.4
    • /
    • pp.267-272
    • /
    • 2007
  • Environmental and anthropogenic changes affect the health and stability of marine ecosystem. In this study we aimed to identify molecular biomarkers for ecotoxicological pollutants risk assessment in the rockfish (Sebastes schlegeli). We designed primers based on conserved sequences by multiple alignments of target genes from related species, and cloned the partial cDNAs of cytochrome P450 (CYP1A1), glutathione S-transferase (GST), metallothionein (MT), superoxide dismutase (SOD), ubiquitin (UB), vitellogenin (VTG) and $\beta$-actin by reverse transcription polymerase chain reaction (RT-PCR) from S. schlegeli. Northern blot results indicated that these six genes expressions were significantly induced by benzo[a]pyrene (BaP, 1 ${\mu}M$) and that the level of each of their transcripts increased in BaP-exposed rockfish in a time-dependent manner. This study suggests that transcriptional changes in these six genes may be used for monitoring environmental exposure to polycyclic aromatic hydrocarbons (PAHs).

Bioactivities of Sulfur Compounds in Cruciferous Vegetables

  • Kim Mee-Ree
    • Proceedings of the Korean Society of Food Science and Nutrition Conference
    • /
    • 2004.11a
    • /
    • pp.150-157
    • /
    • 2004
  • Cruciferous vegetables are rich in organosulfur compounds such as isothiocyanates and sulfides. While the isothiocyanates, corresponding to pungent principle, are generated from myrosinase-catalyzed hydrolysis of glucosinolates, the sulfides can be generated non-enzymatically. Recent studies provide evidences that some sulfur compounds in these vegetables show a chemopreventive action against carcinogenesis; while isothiocyanates such as sulforaphane induce phase 2 enzymes (glutathione S-transferase/quinone reductase), disulfides tends to elevate the level of phase 1 and 2 enzymes. Especially, sulforaphane rich in Cruciferae vegetables has been reported to express anticarcinogenic effect in some organs such as liver, kidney or intestine. When the level of sulfur compounds in Cruciferous and Alliaceous vegetables was determined by GC/MS (SIM), the richest in sulforaphane is broccoli followed by turnip, cabbage, radish, kale, cauliflower and Chinese cabbage. Meanwhile, the sulfides are predominant in Alliaceous vegetables such as onion. In related study, the administration of vegetable extract elevated the GST level by 1.5 fold for broccoli, 1.4 fold for radish, and 1.3 for onion. Thus, the vegetables frequently used in Korean dish contain relatively high amount of anticarcinogenic sulfur compounds. Moreover, the combination of broccoli and radish extracts elevated the GST induction up to 1.84 folds of control. In addition, the Kakdugi, fermented radish Kimchi was observed to show a comparable GST induction despite the decomposition of methylthio-3-butenylisothiocyanate (MTBI). Therefore, the combination of vegetables including broccoli, and fermented radish Kimchi would be useful as a functional food for chemoprevention.

  • PDF

Long-term Supplementation of Epimedium koreanum Nakai in Rats and Its Effects on In Vivo Antioxidant Status with Age

  • Lim, Heung-Bin;Lee, Dong-Wook
    • Food Science and Biotechnology
    • /
    • v.16 no.3
    • /
    • pp.404-408
    • /
    • 2007
  • In this study, we investigated the effects by age of long-tenn supplementation of Epimedium koreanum Nakai (EKN)-containing water on the in vivo antioxidant capacities of rats. All rats were reared in a conventional system, and none of the rats showed any signs of aversion to the EKN solution. Neither the mean nor maximum life spans of the rats were extended by long-tenn administration of the solution. The EKN extract caused decreases in the levels of serum thiobarbituric acid reactive substances in the rats. The activities of superoxide dismutase, catalase, and glutathione (GSH) peroxidase within the liver cytosol decreased with age in both the control and EKN-supplemented groups. GSH peroxidase activity, however, was higher at old age in the EKN-supplemented group. The activities of GSH reductase and GSH-S-transferase, and the levels of free-sulfhydryl (SH) and total-SH group gradually decreased with age in both groups. However, there was some tendency for higher levels in the EKN supplemented group at a corresponding age. These results indicate that long-tenn supplementation of EKN water extracts alone does not exhibit discernible adverse effects in rats, and has some enhancing effects on the antioxidant capacities of the blood and liver, but it does not have life-prolonging effects.

Effects of Several Inhibitors of Human Liver Microsomal Cytochrome P450 3A4 on Catalytic Activities of the Enzyme (인체 간 조직의 cytochrome P450 3A4의 활성에 대한 몇가지 억제제의 영향)

  • 오현숙;이갑상;김복량
    • Toxicological Research
    • /
    • v.11 no.1
    • /
    • pp.23-29
    • /
    • 1995
  • Microsomes from human liver sample HL 110 oxidized aflatoxin $B_1$ $(AFB_1)$ to $AFB_1$ exo-8, 9-epoxide which was detected as a glutathione (GSH) conjugate with excess GSH S-transferase and to aflatoxin $Q_1$ ($AFB_1$; 3$\alpha$-hydroxyafiatoxin $B_1$), and testosterone to 6$\beta$-hydroxytestosterone. Anti-P450 3A4 nearly completely inhibited all of the reactions. Some fiavonoids inhibited all of the reactions. While other fiayonolds stimulated 8, 9-epoxidation and inhibited 3$\alpha$-hydroxylation. Gestodene inhibited all of the reactions when gestodene was metabolized by human liver microsomal P450 3A4 prior to adding substrate. But, ges-todene was added in the enzyme mixtures in the presence of $AFB_1$, it could not inhibit 8, 9-epoxidation of $AFB_1$. Nifedipine and troleandomycin inhibited both of the reactions of $AFB_1$ but only 3$\alpha$-hydroxylation was inhibited by the oxidation product of nifedipine. Although, troleandomycin was known as a mechanism-based inhibitor, the chemical did not show any detectable inhibitory effect on 6$\beta$-hydroxylation of testosterone. The results suggest that there are several different substrate-binding sites on P450 3A4.

  • PDF