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Poly(ADP-ribose) protects vascular smooth muscle cells from oxidative DNA damage

  • Zhang, Chao;Luo, Tao;Cui, Shijun;Gu, Yongquan;Bian, Chunjing;Chen, Yibin;Yu, Xiaochun;Wang, Zhonggao
    • BMB Reports
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    • v.48 no.6
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    • pp.354-359
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    • 2015
  • Vascular smooth muscle cells (VSMCs) undergo death during atherosclerosis, a widespread cardiovascular disease. Recent studies suggest that oxidative damage occurs in VSMCs and induces atherosclerosis. Here, we analyzed oxidative damage repair in VSMCs and found that VSMCs are hypersensitive to oxidative damage. Further analysis showed that oxidative damage repair in VSMCs is suppressed by a low level of poly (ADP-ribosyl)ation (PARylation), a key post-translational modification in oxidative damage repair. The low level of PARylation is not caused by the lack of PARP-1, the major poly(ADP-ribose) polymerase activated by oxidative damage. Instead, the expression of poly(ADP-ribose) glycohydrolase, PARG, the enzyme hydrolyzing poly(ADP-ribose), is significantly higher in VSMCs than that in the control cells. Using PARG inhibitor to suppress PARG activity facilitates oxidative damage-induced PARylation as well as DNA damage repair. Thus, our study demonstrates a novel molecular mechanism for oxidative damage-induced VSMCs death. This study also identifies the use of PARG inhibitors as a potential treatment for atherosclerosis. [BMB Reports 2015; 48(6): 354-359]

Molecular Cloning and Expression of Human Poly (ADP-ribose) Synthetase cDNA in E. Coli (인간 Poly(ADP-ribose) Synthetase cDNA의 클로닝 및 대장균에서의 발현)

  • 이성용;김완주;이태성;박상대;이정섭;박종군
    • The Korean Journal of Zoology
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    • v.39 no.3
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    • pp.248-256
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    • 1996
  • The present study was performed to clone and express human poly (ADP-ribose) synthetase (PARS) cDNA in E coli. For these purposes, the CDNA for human poly (ADP-ribose) synthetase, encoding the entire protein, was cloned into pGEM-7Zf(+). The resulting recombinant plasmid pPARS6.1 was restriction enzyme mapped and its identity was confirmed by Southern blot analysis. The pPARS6. 1 contained full-length CDNA of human PARS and the nudeotide sequences were identical with those reported previously. The recombinant protein which migrated as a unique 120 kDa band on 10% SDS-polyacrylamide gels, was identified as PARS by Southwestern blots using nick-translated DNA probes and by activity gels and activity blots using 32 P-NAD as a substrate for poly (ADP-ribose) synthetase (PARS). The signals corresponding to 120 and 98 kDa proteins were obtained following IPTG (0.4 mM) induction of the PARS cDNA cloned into Xba I-digested pGEM-7Zf(+) vector. Nonspecific signals corresponding to 45 and 38 kDa proteins were also shown in both IPTG-induced and noninduced cells. The nonspecific proteins may be products of incomplete translation or proteolytic products of intact PARS.

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Study on Change of Poly ADP Ribose Polymerase in the Rat with Thrombotic Stroke by Full Wave Cockroft Walton method's Transcranial Magnetic Stimulation

  • Kim, Whi-Young;Kim, Jun-Hyoung
    • Journal of Magnetics
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    • v.19 no.1
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    • pp.20-27
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    • 2014
  • This study examined the relationships between protein expression and Poly ADP ribose polymerase in brain cell death in brains damaged by thrombotic stroke and treated with the Full Wave- Cockroft Walton (FWCW) method of Transcranial Magnetic Stimulation (TMS). The two-way switching element for TMS drove a half-bridge inverter of the current resonance of direct current voltage (+) and direct current voltage (-), and the experiment was conducted by stimulating the mice with thrombotic stroke through a range of pulses. Thrombotic stroke was caused of ligation of the common carotid artery of male SD mice, and blood reperfusion was conducted five minutes later. Protein expression was examined in immune reaction cells, which reacted to an antibody to Poly ADP ribose polymerase in the cerebrum cells, and western blotting. Observations of the PARP changes after thrombotic stroke showed that the number of Poly ADP ribose polymerase reactions were significantly lower (p < 0.05) in the group treated with TMS of the FWCW than the group with thrombotic stroke 24 hours after its onset. The application of FWCW-TMS helped prevent the necrosis of nerve cells and might prevent the brain damage that occurs as a result of thrombotic stroke, and improve the function recovery and disorder of brain cells.

Poly(ADP-ribosyl)ation of p53 Contributes to TPEN-Induced Neuronal Apoptosis

  • Kim, Hyun-Lim;Ra, Hana;Kim, Ki-Ryeong;Lee, Jeong-Min;Im, Hana;Kim, Yang-Hee
    • Molecules and Cells
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    • v.38 no.4
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    • pp.312-317
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    • 2015
  • Depletion of intracellular zinc by N,N,N,N-tetrakis(2-pyridylmethyl) ethylenediamine (TPEN) induces p53-mediated protein synthesis-dependent apoptosis of mouse cortical neurons. Here, we examined the requirement for poly(ADP-ribose) polymerase (PARP)-1 as an upstream regulator of p53 in zinc depletion-induced neuronal apoptosis. First, we found that chemical inhibition or genetic deletion of PARP-1 markedly attenuated TPEN-induced apoptosis of cultured mouse cortical neurons. Poly(ADP-ribosyl)ation of p53 occurred starting 1 h after TPEN treatment. Suggesting the critical role of PARP-1, the TPEN-induced increase of stability and activity of p53 as well as poly(ADP-ribosyl)ation of p53 was almost completely blocked by PARP inhibition. Consistent with this, the induction of downstream pro-apoptotic proteins PUMA and NOXA was noticeably reduced by chemical inhibitors or genetic deletion of PARP-1. TPEN-induced cytochrome C release into the cytosol and caspase-3 activation were also blocked by inhibition of PARP-1. Taken together, these findings indicate that PARP-1 is essential for TPEN-induced neuronal apoptosis.

Effects of 3-Aminobenzamide on DNA Strand Breaks and Excision Repair in CHO cells Exposed to Methyl Methanesulfonate and Ultraviolet-light (MMS와 자외선을 처리한 CHO세포에 있어서 DNA사 절단과 절제회복에 미치는 3-aminobenzamide의 영향)

  • Park, Sang-Dai;Jang, Young-Ju;Roh, Jung-Koo
    • The Korean Journal of Zoology
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    • v.26 no.3
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    • pp.171-179
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    • 1983
  • Amounts of DNA single strand breaks and unscheduled DNA synthesis in CHO cells exposed to MMS were increased in the presence of 3-aminobenzamide, a potent inhibitor of poly (ADP-ribose) polymerase. However, those in cells irradiated with UV-light were decreased. These results suggest that poly (ADP-ribose) polymerase acts negatively on the MMS-induced base excision repair but positively on the UV-induced nucleotide excision repair. In the combined treatment with MMS and UV-light in the presence of this inhibitor, amounts of strand breaks were just the same as those in the absence of the inhibitor. But those of unscheduled DNA synthesis were increased up to the amount induced by UV-light alone. These results may suggest that poly (ADP-ribose) polymerase affects the incision step of excision repair induced by MMS and UV-light independently, and that it may potentiate the complete cleaving of UV-induced pyrimidine dimers possibly by the repair enzymes which might have been partially inactivated by MMS.

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Synthesis of Phosphoric Polymer Coating Solution with Antimicrobial Activity and Flame Retardant Efficiency (항균성과 난연성을 함유하고 있는 인계고분자 코팅용액의 합성)

  • Kim, Sang-Kyum;Lee, In-Soo;Seo, Sang-Hee;Choi, Seong-Ho
    • Polymer(Korea)
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    • v.35 no.5
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    • pp.431-437
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    • 2011
  • A polymeric coating solution based on poly(acryloyl diphosphoric acid)(poly(ADP)) was prepared via a radical polymerization of acryloyl diphosphoric acid using ammonium persulfate (APS) as an initiator in water at 70 $^{\circ}C$. The prepared polymeric coating solution exhibited significant antibacterial activity against salmonella typhimurium, pseudomonas aeruginosa, escherichia coli, and staphylococcus aureus. It also exhibited good antifungal activity against Asperigillus niger and good antiviral activity against the influenza (H1N1) virus. Additionally, it exhibited good flame retardant efficiency after applying it as a coating to a cotton fabric.

Changes in Poly ADP Ribose Polymerase Immune Response Cells of Cerebral Ischaemia Induced Rat by Transcranial Magnetic Stimulation of Alternating Current Approach

  • Koo, Hyun-Mo;Kim, Whi-Young
    • Journal of Magnetics
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    • v.19 no.4
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    • pp.357-364
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    • 2014
  • This study examined effect of a transcranial magnetic stimulation device with a commercial-frequency approach on the neuronal cell death caused ischemia. For a simple transcranial magnetic stimulation device, the experiment was conducted on an ischemia induced rat by transcranial magnetic stimulation of a commercial-frequency approach, controlling the firing angle using a Triac power device. The transcranial magnetic stimulation device was controlled at a voltage of 220 V 60 Hz and the trigger of the Triac gate was varied from $45^{\circ}$ up to $135^{\circ}$. Cerebral ischemia was caused by ligating the common carotid artery of male SD rats and reperfusion was performed again to blood after 5 minutes. Protein Expression was examined by Western blotting and the immune response cells reacting to the antibodies of Poly ADP ribose polymerase in the cerebral nerve cells. As a result, for the immune response cells of Poly ADP ribose polymerase related to necrosis, the transcranial magnetic stimulation device suppressed necrosis and had a protective effect on nerve cells. The effect was greatest within 12 hours after ischemia. Therefore, it is believed that in the case of brain damage caused by ischemia, the function of brain cells can be restored and the impairment can be improved by the application of transcranial magnetic stimulation.

Dose-dependent UV Stabilization of p53 in Cultured Human Cells Undergoing Apoptosis Is Mediated by Poly(ADP-ribosyl)ation

  • Won, Jungyeon;Chung, So Young;Kim, Seung Beom;Byun, Boo Hyeong;Yoon, Yoo Sik;Joe, Cheol O.
    • Molecules and Cells
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    • v.21 no.2
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    • pp.218-223
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    • 2006
  • The effect of poly(ADP-ribosyl)ation on the stability of p53 in SK-HEP1 cells treated with UV light was examined. Intracellular levels of p53 increased in cells treated with a low dose of UV light ($20J/m^2$), whereas they increased but then declined after a higher dose of UV ($100J/m^2$). Intracellular levels of p53 in the UV treated SK-HEP1 cells were dependent on the UV dose. Use of proteasome inhibitors revealed that p53 is degraded by proteasomal proteolysis after high doses of UV light. We present evidence that, at low doses, poly(ADP-ribose)polymerase (PARP) poly(ADP-ribosyl) ates p53 and protects it from proteasomal degradation before caspase-3 is activated, whereas at high doses the cells undergo UV induced apoptosis and PARP is cleaved by caspase-3 before it can protect p53 from degradation. Destabilization of p53 by cleavage of PARP may be important in cell fate decision favoring apoptosis.

ADP-Ribosylation: Activation, Recognition, and Removal

  • Li, Nan;Chen, Junjie
    • Molecules and Cells
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    • v.37 no.1
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    • pp.9-16
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    • 2014
  • ADP-ribosylation is a type of posttranslational modification catalyzed by members of the poly(ADP-ribose) (PAR) polymerase superfamily. ADP-ribosylation is initiated by PARPs, recognized by PAR binding proteins, and removed by PARG and other ADP-ribose hydrolases. These three groups of proteins work together to regulate the cellular and molecular response of PAR signaling, which is critical for a wide range of cellular and physiological functions.

Studies on Benzofuran-7-carboxamides as Poly(ADP-ribose) Polymerase-1 (PARP-1) Inhibitors

  • Lee, Sun-Kyung;Yi, Kyu-Yang;Lee, Byung-Ho;Oh, Kwang-Seok
    • Bulletin of the Korean Chemical Society
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    • v.33 no.4
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    • pp.1147-1153
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    • 2012
  • Benzofuran-7-carboxamide was identified as a novel scaffold of poly(ADP-ribose) polymerase-1 (PARP-1) inhibitor. A series of compounds with various 2-substituents including (tertiary amino)methyl moieties substituted with aryl ring and aryl groups containing tertiary amines, were synthesized and biologically evaluated to elucidate the structure-activity relationships and optimize the potency. 2-[4-(Pyrrolidin-1-ylmethyl)phenyl]-benzofuran-7-carboxamide (42) was the most potent as an IC50 value of 40 nM among those.