Fenofibrate decreases radiation sensitivity via peroxisome proliferator-activated receptor ${\alpha}$-mediated superoxide dismutase induction in HeLa cells

Liu, Xianguang,Jang, Seong-Soon,An, Zhengzhe,Song, Hye-Jin,Kim, Won-Dong,Yu, Jae-Ran,Park, Woo-Yoon The Korean Society for Radiation Oncology 2012 Radiation Oncology Journal Vol.30 No.2

Purpose: The fibrates are ligands for peroxisome proliferator-activated receptor (PPAR) ${\alpha}$ and used clinically as hypolipidemic drugs. The fibrates are known to cause peroxisome proliferation, enhance superoxide dismutase (SOD) expression and catalase activity. The antioxidant actions of the fibrates may modify radiation sensitivity. Here, we investigated the change of the radiation sensitivity in two cervix cancer cell lines in combination with fenofibrate (FF). Materials and Methods: Activity and protein expression of SOD were measured according to the concentration of FF. The mRNA expressions were measured by using real time reverse-transcription polymerase chain reaction. Combined cytotoxic effect of FF and radiation was measured by using clonogenic assay. Results: In HeLa cells total SOD activity was increased with increasing FF doses up to 30 ${\mu}M$. In the other hand, the catalase activity was increased a little. As with activity the protein expression of SOD1 and SOD2 was increased with increasing doses of FF. The mRNAs of SOD1, SOD2, $PPAR{\alpha}$ and $PPAR{\gamma}$ were increased with increasing doses of FF. The reactive oxygen species (ROS) produced by radiation was decreased by preincubation with FF. The surviving fractions (SF) by combining FF and radiation was higher than those of radiation alone. In Me180 cells SOD and catalase activity were not increased with FF. Also, the mRNAs of SOD1, SOD2, and $PPAR{\alpha}$ were not increased with FF. However, the mRNA of $PPAR{\gamma}$ was increased with FF. Conclusion: FF can reduce radiation sensitivity by ROS scavenging via SOD induction in HeLa. SOD induction by FF is related with $PPAR{\alpha}$.

Fenofibrate is radioprotective via SOD induction in HeLa cells

Xianguang Liu,Zhengzhe An,Won Dong Kim,Jae-Ran Yu,Woo-Yoon Park 대한방사선방어학회 2009 대한방사선방어학회 학술발표회 논문요약집 Vol.2009 No.11

Genetic diversity of Acanthamoeba isolates from ocean sediments

Hua LIU,Young-Ran HA,Sung-Tae LEE,Yean-Chul HONG,Hyun-Hee KONG,Dong-Il CHUNG 대한기생충학열대의학회 2006 The Korean Journal of Parasitology Vol.44 No.2

Fenofi brate decreases radiation sensitivity via peroxisome proliferator-activated receptor α-mediated superoxide dismutase induction in HeLa cells

Xianguang Liu,Seong Soon Jang,Zhengzhe An,Hyejin Song,Won-Dong Kim,Jae-Ran Yu,Woo-Yoon Park 대한방사선종양학회 2012 Radiation Oncology Journal Vol.30 No.2

Purpose: The fibrates are ligands for peroxisome proliferator-activated receptor (PPAR) α and used clinically as hypolipidemic drugs. The fibrates are known to cause peroxisome proliferation, enhance superoxide dismutase (SOD) expression and catalase activity. The antioxidant actions of the fibrates may modify radiation sensitivity. Here, we investigated the change of the radiation sensitivity in two cervix cancer cell lines in combination with fenofibrate (FF). Materials and Methods: Activity and protein expression of SOD were measured according to the concentration of FF. The mRNA expressions were measured by using real time reverse-transcription polymerase chain reaction. Combined cytotoxic effect of FF and radiation was measured by using clonogenic assay. Results: In HeLa cells total SOD activity was increased with increasing FF doses up to 30 μM. In the other hand, the catalase activity was increased a little. As with activity the protein expression of SOD1 and SOD2 was increased with increasing doses of FF. The mRNAs of SOD1, SOD2, PPARα and PPARγ were increased with increasing doses of FF. The reactive oxygen species (ROS) produced by radiation was decreased by preincubation with FF. The surviving fractions (SF) by combining FF and radiation was higher than those of radiation alone. In Me180 cells SOD and catalase activity were not increased with FF. Also, the mRNAs of SOD1, SOD2, and PPARα were not increased with FF. However, the mRNA of PPARγ was increased with FF. Conclusion: FF can reduce radiation sensitivity by ROS scavenging via SOD induction in HeLa. SOD induction by FF is related with PPARα.

Animal Products and Processing : Effect of Irradiation on the Mixture of Egg White Proteins Responsible for Foaming Property

Xian De Liu,Rong Xiu Han,Dong Il Jin,Soo Kee Lee,Cheo Run Jo 한국동물자원과학회 2009 한국축산학회지 Vol.51 No.6

Effect of troglitazone on radiation sensitivity in cervix cancer cells

An, Zhengzhe,Liu, Xianguang,Song, Hye-Jin,Choi, Chi-Hwan,Kim, Won-Dong,Yu, Jae-Ran,Park, Woo-Yoon The Korean Society for Radiation Oncology 2012 Radiation Oncology Journal Vol.30 No.2

Purpose: Troglitazone (TRO) is a peroxisome proliferator-activated receptor ${\gamma}$ ($PPAR{\gamma}$) agonist. TRO has antiproliferative activity on many kinds of cancer cells via G1 arrest. TRO also increases $Cu^{2+}/Zn^{2+}$-superoxide dismutase (CuZnSOD) and catalase. Cell cycle, and SOD and catalase may affect on radiation sensitivity. We investigated the effect of TRO on radiation sensitivity in cancer cells in vitro. Materials and Methods: Three human cervix cancer cell lines (HeLa, Me180, and SiHa) were used. The protein expressions of SOD and catalase, and catalase activities were measured at 2-10 ${\mu}M$ of TRO for 24 hours. Cell cycle was evaluated with flow cytometry. Reactive oxygen species (ROS) was measured using 2',7'-dichlorofluorescin diacetate. Cell survival by radiation was measured with clonogenic assay. Results: By 5 ${\mu}M$ TRO for 24 hours, the mRNA, protein expression and activity of catalase were increased in all three cell lines. G0-G1 phase cells were increased in HeLa and Me180 by 5 ${\mu}M$ TRO for 24 hours, but those were not increased in SiHa. By pretreatment with 5 ${\mu}M$ TRO radiation sensitivity was increased in HeLa and Me180, but it was decreased in SiHa. In Me180, with 2 ${\mu}M$ TRO which increased catalase but not increased G0-G1 cells, radiosensitization was not observed. ROS produced by radiation was decreased with TRO. Conclusion: TRO increases radiation sensitivity through G0-G1 arrest or decreases radiation sensitivity through catalase-mediated ROS scavenging according to TRO dose or cell types. The change of radiation sensitivity by combined with TRO is not dependent on the PPAR ${\gamma}$ expression level.

Single-Atom Switches and Single-Atom Gaps Using Stretched Metal Nanowires

Wang, Qingling,Liu, Ran,Xiang, Dong,Sun, Mingyu,Zhao, Zhikai,Sun, Lu,Mei, Tingting,Wu, Pengfei,Liu, Haitao,Guo, Xuefeng,Li, Zong-Liang,Lee, Takhee American Chemical Society 2016 ACS NANO Vol.10 No.10

<P>Utilizing individual atoms or molecules as functional units in electronic circuits meets the increasing technical demands for the miniaturization of traditional semiconductor devices. To be of technological interest, these functional devices should be high-yield, consume low amounts of energy, and operate at room temperature. In this study, we developed nanodevices called quantized conductance atomic switches (QCAS) that satisfy these requirements. The QCAS operates by applying a feedback-controlled voltage to a nanoconstriction within a stretched nanowire. We demonstrated that individual metal atoms could be removed from the nanoconstriction and that the removed metal atoms could be refilled into the nanoconstriction, thus yielding a reversible quantized conductance switch. We determined the key parameters for the QCAS between the 'on' and 'off' states at room temperature under a small operating voltage. By controlling the applied bias voltage, the atoms can be further completely removed from the constriction to break the nanowire, generating single-atom nanogaps. These atomic nanogaps are quite stable under a sweeping voltage and can be readjusted with subangstrom accuracy, thus fulfilling the requirement of both reliability and flexibility for the high-yield fabrication of molecular devices.</P>

Loss of RTN3 phenocopies chronic kidney disease and results in activation of the IGF2-JAK2 pathway in proximal tubular epithelial cells

Fan Liang-Liang,Du Ran,Liu Ji-Shi,Jin Jie-Yuan,Wang Chen-Yu,Dong Yi,He Wan-Xia,Yan Ri-Qiang,Xiang Rong 생화학분자생물학회 2022 Experimental and molecular medicine Vol.54 No.-

Reticulon 3 (RTN3) is an endoplasmic reticulum protein that has previously been shown to play roles in neurodegenerative diseases, but little is known about its function in the kidneys. The aim of the present study was to clarify the roles of RTN3 in chronic kidney disease (CKD) and kidney fibrosis. In this study, RTN3 levels were measured in kidney tissues from healthy controls and CKD or kidney fibrosis patients. An RTN3-null mouse model was generated to explore the pathophysiological roles of RTN3 in the kidneys. The underlying mechanisms were studied in primary proximal tubular epithelial cells and HEK293 cells in vitro. The results showed that (1) a reduction in RTN3 in mice induces CKD and kidney fibrosis; (2) decreased RTN3 expression is found in patients with CKD; (3) RTN3 plays critical roles in regulating collagen biosynthesis and mitochondrial function; and (4) mechanistically, RTN3 regulates these phenotypes by interacting with GC-Rich Promoter Binding Protein 1 (GPBP1), which activates the IGF2-JAK2-STAT3 pathway. Our study indicates that RTN3 might play crucial roles in CKD and kidney fibrosis and that a reduction in RTN3 in the kidneys might be a risk factor for CKD and kidney fibrosis.

Effect of troglitazone on radiation sensitivity in cervix cancer cells

Zhengzhe An,Xianguang Liu,Hyejin Song,Chihwan Choi,Won-Dong Kim,Jae-Ran Yu,Woo-Yoon Park 대한방사선종양학회 2012 Radiation Oncology Journal Vol.30 No.2

Purpose: Troglitazone (TRO) is a peroxisome proliferator-activated receptor γ (PPARγ) agonist. TRO has antiproliferative activity on many kinds of cancer cells via G1 arrest. TRO also increases Cu²⁺/Zn²⁺-superoxide dismutase (CuZnSOD) and catalase. Cell cycle, and SOD and catalase may affect on radiation sensitivity. We investigated the effect of TRO on radiation sensitivity in cancer cells in vitro. Materials and Methods: Three human cervix cancer cell lines (HeLa, Me180, and SiHa) were used. The protein expressions of SOD and catalase, and catalase activities were measured at 2-10 μM of TRO for 24 hours. Cell cycle was evaluated with flow cytometry. Reactive oxygen species (ROS) was measured using 2',7' dichlorofluorescin diacetate. Cell survival by radiation was measured with clonogenic assay. Results: By 5 μM TRO for 24 hours, the mRNA, protein expression and activity of catalase were increased in all three cell lines. G0-G1 phase cells were increased in HeLa and Me180 by 5 μM TRO for 24 hours, but those were not increased in SiHa. By pretreatment with 5 μM TRO radiation sensitivity was increased in HeLa and Me180, but it was decreased in SiHa. In Me180, with 2 μM TRO which increased catalase but not increased G0-G1 cells, radiosensitization was not observed. ROS produced by radiation was decreased with TRO. Conclusion: TRO increases radiation sensitivity through G0-G1 arrest or decreases radiation sensitivity through catalasemediated ROS scavenging according to TRO dose or cell types. The change of radiation sensitivity by combined with TRO is not dependent on the PPAR γ expression level.

Chlorpropamide 2-hydroxylation is catalysed by CYP2C9 and CYP2C19 <i>in vitro</i>: chlorpropamide disposition is influenced by CYP2C9, but not by CYP2C19 genetic polymorphism

Shon, Ji-Hong,Yoon, Young-Ran,Kim, Min-Jung,Kim, Kyoung-Ah,Lim, Young-Chae,Liu, Kwang-Hyeon,Shin, Dong-Hoon,Lee, Chung Han,Cha, In-June,Shin, Jae-Gook Blackwell Science Ltd 2005 British journal of clinical pharmacology Vol.59 No.5

<P>Aims</P><P>We evaluated the involvement of cytochrome P450 (CYP) isoforms 2C9 and 2C19 in chlorpropamide 2-hydroxylation <I>in vitro</I> and in chlorpropamide disposition <I>in vivo</I>.</P><P>Methods</P><P>To identify CYP isoforms(s) that catalyse 2-hydroxylation of chlorpropamide, the incubation studies were conducted using human liver microsomes and recombinant CYP isoforms. To evaluate whether genetic polymorphisms of CYP2C9 and/or CYP2C19 influence the disposition of chlorpropamide, a single oral dose of 250 mg chlorpropamide was administered to 21 healthy subjects pregenotyped for CYP2C9 and CYP2C19.</P><P>Results</P><P>In human liver microsomal incubation studies, the formation of 2-hydroxychlorpropamide (2-OH-chlorpropamide), a major chlorpropamide metabolite in human, has been best described by a one-enzyme model with estimated <I>K</I><SUB><I>m</I></SUB> and <I>V</I><SUB>max</SUB> of 121.7 ± 19.9 µ<SMALL>M</SMALL> and 16.1 ± 5.0 pmol min<SUP>−1</SUP> mg<SUP>−1</SUP> protein, respectively. In incubation studies using human recombinant CYP isoforms, however, 2-OH-chlorpropamide was formed by both CYP2C9 and CYP2C19 with similar intrinsic clearances (CYP2C9 <I>vs.</I> CYP2C19: 0.26 <I>vs.</I> 0.22 µl min<SUP>−1</SUP> nmol<SUP>−1</SUP> protein). Formation of 2-OH-chlorpropamide in human liver microsomes was significantly inhibited by sulfaphenazole, but not by <I>S</I>-mephenytoin, ketoconazole, quinidine, or furafylline. In <I>in vivo</I> clinical trials, eight subjects with the <I>CYP2C9</I>*<I>1/</I>*<I>3</I> genotype exhibited significantly lower nonrenal clearance [*<I>1/</I>*<I>3 vs.</I>*<I>1/</I>*<I>1</I>: 1.8 ± 0.2 <I>vs.</I> 2.4 ± 0.1 ml h<SUP>−1</SUP> kg<SUP>−1</SUP>, <I>P</I> < 0.05; 95% confidence interval (CI) on the difference 0.2, 1.0] and higher metabolic ratios (of chlorpropamide/2-OH-chlorpropamide in urine: *<I>1/</I>*<I>3 vs.</I>*<I>1/</I>*<I>1</I>: 1.01 ± 0.19 <I>vs.</I> 0.56 ± 0.08, <I>P</I> < 0.05; 95% CI on the difference − 0.9, − 0.1) than did 13 subjects with <I>CYP2C9</I>*<I>1/</I>*<I>1</I> genotype. In contrast, no differences in chlorpropamide pharmacokinetics were observed for subjects with the <I>CYP2C19</I> extensive metabolizer <I>vs.</I> poor metabolizer genotypes.</P><P>Conclusions</P><P>These results suggest that chlorpropamide disposition is principally determined by CYP2C9 activity <I>in vivo</I>, although both CYP2C9 and CYP2C19 have a catalysing activity of chlorpropamide 2-hydroxylation pathway.</P>