• Title/Summary/Keyword: protein damage

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Hsp90 Inhibitor Geldanamycin Enhances the Antitumor Efficacy of Enediyne Lidamycin in Association with Reduced DNA Damage Repair

  • Han, Fei-Fei;Li, Liang;Shang, Bo-Yang;Shao, Rong-Guang;Zhen, Yong-Su
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.17
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    • pp.7043-7048
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    • 2014
  • Inhibition of heat shock protein 90 (Hsp90) leads to inappropriate processing of proteins involved in DNA damage repair pathways after DNA damage and may enhance tumor cell radio- and chemotherapy sensitivity. To investigate the potentiation of antitumor efficacy of lidamycin (LDM), an enediyne agent by the Hsp90 inhibitorgeldanamycin (GDM), and possible mechanisms, we have determined effects on ovarian cancer SKOV-3, hepatoma Bel-7402 and HepG2 cells by MTT assay, apoptosis assay, and cell cycle analysis. DNA damage was investigated with H2AX C-terminal phosphorylation (${\gamma}H2AX$) assays. We found that GDM synergistically sensitized SKOV-3 and Bel-7402 cells to the enediyne LDM, and this was accompanied by increased apoptosis. GDM pretreatment resulted in a greater LDM-induced DNA damage and reduced DNA repair as compared with LDM alone. However, in HepG2 cells GDM did not show significant sensitizing effects both in MTT assay and in DNA damage repair. Abrogation of LDM-induced $G_2/M$ arrest by GDM was found in SKOV-3 but not in HepG2 cells. Furthermore, the expression of ATM, related to DNA damage repair responses, was also decreased by GDM in SKOV-3 and Bel-7402 cells but not in HepG2 cells. These results demonstrate that Hsp90 inhibitors may potentiate the antitumor efficacy of LDM, possibly by reducing the repair of LDM-induced DNA damage.

Lipid and Lipase Distribution on Endosperm Cell of Panax ginseng Seed for the Electron Microscope (전자현미경을 이용한 인삼종자 배유세포내의 지질 및 지질가수분해 효소의 분포)

  • 유성철;노미전
    • Journal of Ginseng Research
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    • v.16 no.2
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    • pp.129-137
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    • 1992
  • This study was carried out to investigate the localization of lipids and lipase activity with lipid staining and cytochemical technique in endosperm cells of Panax ginseng C.A. Meyer seed. In endosperm cells of indehiscent seed, protein bodies facing the umbiliform layer are different in electron density during the various degraded processes. Gradually, protein matrix near the cell wall was lysed and electron lucent inclusions appeared on umbiliform layer. The protein body with high electron density and the spherosome with low electron density were observed in endosperm cells. As a result of lipid staining, electron density of spherosome is more intense than those of the protein matrix within the protein body in endosperm cells of indehiscent seed. Free spherical spherosomes within the umbiliform layer have a high electron density. The spherical spherosomes were more electron densed and were uniform in comparison with the cytoplasmic proteinaceous granules in endosperm cells of seed with red seed coat. The major component of spherosome was determined to be lipid. Lipase activity occurs in the spherosome and near the endosperm cell wall facing the umbiliform layer. Cytochemical reaction products of lipase were observed in the spherosome membrane and in the inner regions of spherosome. After protein bodies were digested, lipase activities were observed in free spherosomes and near the cell wall of endosperm cells. Umbiliform layer composing of fibrillized wall and digested materials of the endosperm cell showed a little lipase reaction products.

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Different Protein Expression between Human Eosinophilic Leukemia Cells, EoL-1 and Imatinib-resistant EoL-1 Cells, EoL-1-IR

  • Sung, Kee-Hyung;Kim, In-Sik;Lee, Ji-Sook
    • Biomedical Science Letters
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    • v.24 no.4
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    • pp.426-429
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    • 2018
  • Chronic eosinophilic leukemia (CEL) is characterized by eosinophilia and organ damage. Imatinib is widely used for treating CEL, chronic myeloid leukemia (CML) and acute myeloid leukemia (AML). Unfortunately, the cancer cells gain resistance against the drug after prolonged molecular-targeted therapies. Imatinib-resistant EoL-1 (EoL-1-IR) cells were produced from chronic eosinophilic leukemia cells (EoL-1) after treatment with imatinib for a long duration. Two-dimensional electrophoresis (2-DE) analysis revealed numerous protein variations in the EoL-1 and EoL-1-IR sub-types. Compared to the EoL-1 cells, expression levels of TIP49, RBBP7, ${\alpha}$-enolase, adenosine deaminase, C protein, galactokinase, eukaryotic translation initiation factor, $IFN-{\gamma}$, and human protein homologous to DROER were increased, whereas core I protein, proteasome subunit p42, heterogeneous ribonuclear particle protein, chain B, and nucleoside diphosphate were decreased in the EoL-1-IR cells. Taken together, these results contribute to understanding the pathogenic mechanism of drug-resistant diseases.

Inhibitory Effect of Red Bean (Phaseolus angularis) Hot Water Extracts on Oxidative DNA and Cell Damage (팥(Phaseolus angularis) 열수 추출물의 산화적 DNA와 세포 손상 억제 효과)

  • Park, Young-Mi;Jeong, Jin-Boo;Seo, Joo-Hee;Lim, Jae-Hwan;Jeong, Hyung-Jin;Seo, Eul-Won
    • Korean Journal of Plant Resources
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    • v.24 no.2
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    • pp.130-138
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    • 2011
  • In this study, we evaluated the protective effects of the hot water extract from red bean (Phaseolus angularis) against oxidative DNA and cell damage induced by hydroxyl radical. The antioxidant activities were evaluated by hydroxyl radical and hydrogen peroxide scavenging assay, and $Fe^{2+}$-chelating assay. Although the extract with hot water didn't scavenge the hydroxyl radical, it removed and chelated hydrogen peroxide and ferrous iron necessary for the induction of hydroxyl radical by 71% and 64% at 200 ${\mu}g/ml$, respectively. Its protective effect on oxidative DNA damage was carried using ${\Psi}$X-174 RF I plasmid DNA comparing the conversion level of supercoiled form of the plasmid DNA into open-circular form and linear form and the expression level of phospho-H2AX in NIH 3T3 cells. In ${\Psi}$X-174 RF I plasmid DNA cleavage assay, it inhibited oxidative DNA damage by 96% at 200 ${\mu}g/ml$. Also, it decreased the expression of phospho-H2AX by 50.1% at 200 ${\mu}g/ml$. Its protective effect against oxidative cell damage was measured by MTT assay and the expression level of p21 protein in NIH 3T3 cells. In MTT assay for the protective effect against the oxidative cell damage, it inhibited the oxidative cell death and the abnormal cell growth induced by hydroxyl radical. Also, it inhibited p21 protein expression by 98% at 200 ${\mu}g/ml$. In conclusion, the results of the present studies indicate that hot water extract from red bean exhibits antioxidant properties and inhibit oxidative DNA damage and the cell death caused by hydroxyl radical.

Effect of Solanum lyratum Extract on Dimethylniatrosamine-Induced Liver Damage in Rats (Dimethylnitrosamine에 의해 유도된 흰쥐 간독성에 대한 배풍등 추출물의 보호효과)

  • Shin, Mi-Ok;Park, Jong-Hee;Moon, Jeon-Ok
    • Korean Journal of Pharmacognosy
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    • v.34 no.1 s.132
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    • pp.60-64
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    • 2003
  • Solanum lyratum(Solanaceae) has been used as a traditional analgesic, antipyretic and hepatoprotective agents in Korea. In this study, we investigated the hepatoprotective effect of ethylacetate extract of Solanum lyratum (SL) on the dimethylnitrosamine (DMN)-induced liver damage in rats. Oral administration of SL (150, 300 mg/kg daily for 4 weeks) into the DMN-treated rats remarkably prevented the elevation of serum alanine transaminase, aspartate transaminase and alkaline phosphatase levels. SL also increased serum protein level and reduced the hepatic level of malondialdehyde in DMN-treated rats. Furthermore, DMN-induced elevation of hydroxyproline content was reduced by the treatment of SL. In conclusion, these results demonstrated that SL exhibited in vivo hepatoprotective effect against DMN-induced liver injury, and suggest that SL may be useful in the prevention of liver damage.

Effect of Skin Burn on the Skin and Liver (피부화상이 피부 및 간에 미치는 영향)

  • Nam, Chul-Hyun;Seo, Hyun-Gyu;Hwang, Tae-Yeun;Choi, Hyun-Lim;Lee, Dong-Ho
    • Journal of Korean Physical Therapy Science
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    • v.8 no.2
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    • pp.1091-1097
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    • 2001
  • The main experiments was investigated the skin tissue damage changing for the skin bum having influence on the skin and the liver and also observed the radical liver weight, ALT in the serum, the fluctuating of AST for the skin bum causing to the liver damage. Anatomically the edema formation of skin after thermal injury was showed, and skin bum increased liver weight (% of body weight, p<0.05) and the activity of serum aniline aminotrasferase (p<0.05), and also histologically induced wes of epidermal layer, protein degeneration of connective tissue, local hemorrhage and degeneration of glandular epithelium in the skin tissue. Liver tissue showed the evidences of postbum damage, they were sinusoidal dilatation, cell swelling, infiltration of inflammatory cells.

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Hepatoprotective activity of methanol extracts of Glinus oppositifolius and Trianthema decandra against paracetamol induced liver damage

  • Gupta, M;Mazumder, UK;Haldar, PK;Manikandan, L;Senthilkumar, GP;Kandar, CC
    • Advances in Traditional Medicine
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    • v.7 no.1
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    • pp.74-78
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    • 2007
  • The plants, Trianthema decandra and Glinus oppositifolius are commonly used by tribal people in India for the treatment of liver diseases. Hepatoprotective activity of methanol extracts of Glinus oppositifolius and Trianthema decandra at the dose of 250 and 500 mg/kg body weight administered orally was evaluated against paracetamol induced liver damage in rats. Biochemical parameters such as serum glutamate oxaloacetate transaminase, serum glutamate pyruvate transaminase, serum alkaline phosphatase, bilirubin, total serum protein, lipid peroxide and glutathione content of the liver were estimated to determine liver function and metabolism. From the biochemical observations, it was concluded that methanol extracts of Glinus oppositifolius and Trianthema decandra significantly restored the altered biochemical parameters towards normal condition in paracetamol induced liver damage.

Identification of Ozone-induced Skin Damage and Screening of Antioxidant for Ozone (오존에 의한 피부손상 확인 및 이를 방어하는 피부 외용제 소재의 탐색)

  • 최신욱;김창수;정재형;김남경;한상화
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.30 no.1
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    • pp.39-51
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    • 2004
  • Ozone(O$_3$), one of best-known toxic air pollutant, act as a strong oxidant. It is possible that skins exposed to the air can be easily damaged by such oxidative air pollutants. Therefore, in the present study, anti-oxidative effects of natural product. on $O_2$ㆍ and ㆍOH were investigated by EPR. Ozone caused protein damage and lipid oxidation, in HaCaT and B16F10 leading ultimately to programmed cell death. It also reduced the level of antioxidant molecules including ascorbic acid and tocopherol in stratum comeum. However, antioxidants originated from natural products could protect skin from these products could protect skin from these oxidative damages. We concluded that eight natural extracts including Rosa davurica, Ligularia sibrica, Green tea acted as strong antioxidants against ozone.

Hepatoprotective activity of Indigofera aspalathoides extract against CCl4-induced liver damage

  • Gupta, M.;Mazumder, U.K.;Haldar, P.K.;Manikandan, L.;Senthilkumar, G.P.;Kander, C.C.
    • Advances in Traditional Medicine
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    • v.4 no.2
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    • pp.100-103
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    • 2004
  • The plant Indigofera aspalathoides are used by a large number of tribes in India for the treatment of various hepatic disorder. The methanol extract of Indigofera aspalathoides (MEIA) was evaluated for its effect on carbontetrachloride $(CCl_{4})$ induced liver damage. Biochemical parameters such as serum glutamine oxaloacetate trasaminase (SGOT), serum glutamine pyruvate transaminase (SGPT), serum alkaline phosphatase (ALP), total serum protein (TP), thiobarbituric acid reactive substances (TBRS) and glutathione content of the liver were estimated to assess liver function and metabolism. Biochemical observations suggest that methanol extract of Indigofera aspalathoides (MEIA) significantly restored the liver function and metabolism towards normal condition in $CCl_{4}$-induced hepatic damage.

Effect of Cyclohexane Treatment on the Liver Damage in CCl4-Pretreated Rats (CCl4전처치한 흰쥐에 Cyclohexane 투여가 간손상에 미치는 영향)

  • 윤종국;김현희
    • Toxicological Research
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    • v.19 no.2
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    • pp.105-114
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    • 2003
  • TO evaluate an effect of cyclohexane treatment on the degree of liver damage, rats were induced liver damage with 10 or 17 times $CCl_4$ injection (0.1 m1/100 g body wt., 50% $CCl_4$ dis-solved in olive oil) at intervals of every other day. Cyclohexane (1.56 g/kg body wt., i.p.) was administrated to the animals at 48 hours after the last pretreatment of $CCl_4$ . Rats were sacrificed at 4 hours after injection of cyclohexane. On the basis of histopathological findings, liver weight/body weight (LW/ BW, %), activities of serum alanine aminotransferase (ALT), xanthine oxidase (XO) and akaline phosphatase (ALP), and contents of liver protein and manlondialdehyde (MDA), $CCl_4$ -pretreatment induced liver damage. And $CCl_4$ 17 times treated group showed more severe liver damage than $CCl_4$ 10 times treated group. Administration of one dose of cyclohexane to $CCl_4$ 10 times treated animals resulted in the enhanced liver damage; liver necrosis with proliferation of fibroblast and bile duct abnormality, and increase in hepatic MDA content and the activities of serum ALP and ALT, But the enhanced liver damage was not found in $CCl_4$ 17 times treated animals. Serum cyclohexanone concentrations at 4 or 8 hours after injection of cyclohexane were higher in all liver damaged groups than normal group and were somewhat higher In $CCl_4$ 17 times treated animals than $CCl_4$ 10 times treated ones. Among the oxygen free radical metabolizing enzymes, hepatic cytochrome P45O dependent aniline hydroxylase (CYPdAH) activity in cyclohexane metabolizing enzyme system was meaningfully increased by the injection of cyclohexane to the liver damaged rats, with increased Vmax and high affinity to aniline. LW/BW (%) and activities of serum XO and ALT were more significantly increased in liver damaged groups than normal group by administration of cyclohexanone. In conclusion, it is assumed that an enhancement of liver damage by injection of one dose of cyclohexane to liver damaged animals might be caused by oxygen free radicals and cyclohexanone.