PARP抑制对小鼠结肠癌CT26细胞侵袭影响及其机制探讨
摘要
目的:探讨多聚(腺苷二磷酸核糖)聚合酶[poly(ADP-ribose) polymerase, PARP]抑制对小鼠结肠癌CT26细胞侵袭的影响及其可能的机制。
方法:应用细胞-基质粘附试验、细胞运动及侵袭试验,观察PARP抑制剂5-氨基异喹啉酮(5-aminoisoquinolinone, 5-AIQ)抑制CT26细胞PARP前后,其基质粘附、运动及侵袭能力的变化;采用western blot检测5-AIQ对CT26细胞整合素β1(Integrinsβ1)、基质金属蛋白酶(matrix metalloproteinases, MMPs)MMP-2、MMP-9表达的影响,并用明胶酶谱法检测5-AIQ对明胶酶MMP-2和MMP-9活性的影响。
结果:1.细胞-基质粘附实验结果显示,与未处理组比较,经5-AIQ处理过的CT26细胞与纤维连接蛋白的粘附率有明显降低(P<0.01);transwell运动实验结果表明,5-AIQ处理组迁移穿过微孔膜的细胞数较未处理组明显减少(P<0.01);同样transwell侵袭实验表明,5-AIQ处理组的CT26细胞侵袭穿透Matrigel胶,而到达膜下表面的细胞数较未处理组也明显减少(P<0.01).
2.western blot结果提示,PARP抑制剂5-AIQ处理过的CT26细胞其整合素β1、MMP-2和MMP-9的蛋白表达较5-AIQ未处理的CT26细胞有明显减弱,差别均具有统计学意义(P值分别是:整合素β1 P<0.01、MMP-2 P<0.01、MMP-9 P<0.05);而用明胶酶谱法检测明胶酶MMP-2和MMP-9的活性时,在5-AIQ处理组和未处理组之间同样存在明显差异(P值分别是:MMP-2 P<0.05、MMP-9 P<0.01)。
结论:1. PARP抑制剂5-AIQ可降低CT26细胞基质粘附、运动及侵袭能力,PARP在肿瘤侵袭中可能发挥作用。
2. PARP抑制剂5-AIQ使CT26细胞整合素β1、MMP-2和MMP-9的蛋白表达降低,并可使MMP-2和MMP-9酶的活性抑制。提示可能PARP抑制,可能通过抑制肿瘤侵袭转移相关的因子整合素β1、MMP-2和MMP-9的表达和活性,从而影响CT26细胞的侵袭。
Objective: The aim is to study the effect of poly(ADP-ribose) polymerase (PARP) inhibitor on the invasion of murine colon carcinoma CT26 cell lines in vitro,and its mechanism.
Methods: CT26 cell lines were treated with or without PARP inhibitor 5-aminoisoquinolinone (5-AIQ) in vitro.The effects of 5-AIQ on the cell adhesion ,migration and invasion of CT26 were observed by cell- matrix adhesion assay, cell migration assay and matrigel invasion assay, respectively. The expressions of Integrinβ1, MMP-2 and MMP-9 of CT26 cells with or without 5-AIQ were investigated by Western Blot and the activities of MMP-2 and MMP-9 were detected by zymography.
Results: 1. The result of cell-matrix adhesion assay showed that A values of 5-AIQ-treated groups were significantly reduced, when compared with untreated group (P<0.01). Meanwhile, comparing with untreated group, the migration and invasion potential of CT26 were both reduced by 5-AIQ treatment (P<0.01).
2. The expressions of Integrinβ1, MMP-2 and MMP-9 of 5-AIQ-treated group were all significantly lower than the 5-AIQ-untreated group in western blot assay (P value were P<0.01, P<0.01, P<0.05, respectively). Interestingly, the activities of MMP-2 and MMP-9 were also attenuated in 5-AIQ-treated group comparing with 5-AIQ-untreated group (P value were P<0.05, P<0.01, respectively).
Conclusion:1. The data suggest that PARP inhibitor 5-AIQ could reduce the cell-matrix adhesion, migration and invasion in CT26 cells. PARP inhibition might have a contribution for tumor invasion in some degree.
2. 5-AIQ reduced the expressions of Integrinβ1, MMP-2 and MMP-9, and the activities of MMP-2 and MMP-9, which suggested that PARP inhibition suppressed the invasion-relative factors Integrinβ1, MMP-2 and MMP-9, then effected the metastasis of CT26 cells.
方法:应用细胞-基质粘附试验、细胞运动及侵袭试验,观察PARP抑制剂5-氨基异喹啉酮(5-aminoisoquinolinone, 5-AIQ)抑制CT26细胞PARP前后,其基质粘附、运动及侵袭能力的变化;采用western blot检测5-AIQ对CT26细胞整合素β1(Integrinsβ1)、基质金属蛋白酶(matrix metalloproteinases, MMPs)MMP-2、MMP-9表达的影响,并用明胶酶谱法检测5-AIQ对明胶酶MMP-2和MMP-9活性的影响。
结果:1.细胞-基质粘附实验结果显示,与未处理组比较,经5-AIQ处理过的CT26细胞与纤维连接蛋白的粘附率有明显降低(P<0.01);transwell运动实验结果表明,5-AIQ处理组迁移穿过微孔膜的细胞数较未处理组明显减少(P<0.01);同样transwell侵袭实验表明,5-AIQ处理组的CT26细胞侵袭穿透Matrigel胶,而到达膜下表面的细胞数较未处理组也明显减少(P<0.01).
2.western blot结果提示,PARP抑制剂5-AIQ处理过的CT26细胞其整合素β1、MMP-2和MMP-9的蛋白表达较5-AIQ未处理的CT26细胞有明显减弱,差别均具有统计学意义(P值分别是:整合素β1 P<0.01、MMP-2 P<0.01、MMP-9 P<0.05);而用明胶酶谱法检测明胶酶MMP-2和MMP-9的活性时,在5-AIQ处理组和未处理组之间同样存在明显差异(P值分别是:MMP-2 P<0.05、MMP-9 P<0.01)。
结论:1. PARP抑制剂5-AIQ可降低CT26细胞基质粘附、运动及侵袭能力,PARP在肿瘤侵袭中可能发挥作用。
2. PARP抑制剂5-AIQ使CT26细胞整合素β1、MMP-2和MMP-9的蛋白表达降低,并可使MMP-2和MMP-9酶的活性抑制。提示可能PARP抑制,可能通过抑制肿瘤侵袭转移相关的因子整合素β1、MMP-2和MMP-9的表达和活性,从而影响CT26细胞的侵袭。
Objective: The aim is to study the effect of poly(ADP-ribose) polymerase (PARP) inhibitor on the invasion of murine colon carcinoma CT26 cell lines in vitro,and its mechanism.
Methods: CT26 cell lines were treated with or without PARP inhibitor 5-aminoisoquinolinone (5-AIQ) in vitro.The effects of 5-AIQ on the cell adhesion ,migration and invasion of CT26 were observed by cell- matrix adhesion assay, cell migration assay and matrigel invasion assay, respectively. The expressions of Integrinβ1, MMP-2 and MMP-9 of CT26 cells with or without 5-AIQ were investigated by Western Blot and the activities of MMP-2 and MMP-9 were detected by zymography.
Results: 1. The result of cell-matrix adhesion assay showed that A values of 5-AIQ-treated groups were significantly reduced, when compared with untreated group (P<0.01). Meanwhile, comparing with untreated group, the migration and invasion potential of CT26 were both reduced by 5-AIQ treatment (P<0.01).
2. The expressions of Integrinβ1, MMP-2 and MMP-9 of 5-AIQ-treated group were all significantly lower than the 5-AIQ-untreated group in western blot assay (P value were P<0.01, P<0.01, P<0.05, respectively). Interestingly, the activities of MMP-2 and MMP-9 were also attenuated in 5-AIQ-treated group comparing with 5-AIQ-untreated group (P value were P<0.05, P<0.01, respectively).
Conclusion:1. The data suggest that PARP inhibitor 5-AIQ could reduce the cell-matrix adhesion, migration and invasion in CT26 cells. PARP inhibition might have a contribution for tumor invasion in some degree.
2. 5-AIQ reduced the expressions of Integrinβ1, MMP-2 and MMP-9, and the activities of MMP-2 and MMP-9, which suggested that PARP inhibition suppressed the invasion-relative factors Integrinβ1, MMP-2 and MMP-9, then effected the metastasis of CT26 cells.
引文
[1] Virág L and Szabó C. The therapeutic potential of poly(ADP-ribose) polymerase inhibitors. Pharmacol Rev 2002; 54(3):375–429.
[2] Sharma SS, Kumar A and Kaundal RK. Protective effects of 4-amino1,8-napthalimide, a poly (ADP-ribose) polymerase inhibitor in experimental diabetic neuropathy[J]. Life Sci, 2008; 82(11-12): 570-6.
[3] Adaikalakoteswari A, Rema M, Mohan V, et al. Oxidative DNA damage and augmentation of poly(ADP-ribose) polymerase/nuclear factor-kappa B signaling in patients with type 2 diabetes and microangiopathy[J]. Int J Biochem Cell Biol, 2007; 39(9): 1673-84.
[4] von Lukowicz T, Hassa PO, Lohmann C, et al. PARP1 is required for adhesion molecule expression in atherogenesis[J]. Cardiovasc Res. 2008; 78(1):158-66.
[5] Oumouna-Benachour K, Hans CP, Suzuki Y, et al. Poly(ADP-ribose) polymerase inhibition reduces atherosclerotic plaque size and promotes factors of plaque stability in apolipoprotein E-deficient mice: effects on macrophage recruitment, nuclear factor-kappaB nuclear translocation, and foam cell death[J]. Circulation. 2007; 115(18):2442-50.
[6] Kovacs K, Toth A, Deres P, et al. Critical role of PI3-kinase/Akt activation in the PARP inhibitor induced heart function recovery during ischemia-reperfusion[J]. Biochem Pharmacol. 2006; 71(4):441-52.
[7] Tentori L, Leonetti C, Scarsella M, et al. Inhibition of poly(ADP-ribose) polymerase prevents irinotecan-induced intestinal damage and enhances irinotecan / temozolomide efficacy against colon carcinoma [J]. The FASEB Journal, 2006, 20(10):1709-1711.
[8] Albert JM, Cao C, Kim KW, et al. Inhibition of Poly(ADP-Ribose) Polymerase Enhances Cell Death and Improves Tumor Growth Delay in Irradiated Lung Cancer Models [J]. Clinical Cancer Research, 2007, 13(10): 3033-3042.
[9] 郝兰香,王娅兰,李圆圆。大肠癌 PARP 表达与 P-selectin 和 ICAM-1 表达的相关性 [J].基础医学与临床,2006,26(8):882-887。
[10] Rajesh M, Mukhopadhyay P, Godlewski G, et al. Poly(ADP-ribose)polymeraseinhibition decreases angiogenesis[J]. Biochemical and Biophysical Research Communications, 2006, 350(4): 1056–1062.
[11] Gonzalez-Rey E, Martínez-Romero R, O'Valle F, et al. Therapeutic Effect of a Poly(ADP-Ribose) Polymerase-1 Inhibitor on Experimental Arthritis by Downregulating Inflammation and Th1 Response[J]. PLoS ONE. 2007; 2(10):e1071.
[12] Cuzzocrea S, McDonald MC, Mazzon E, et al. Effects of 5-aminoisoquinolione, a water-soluble, potent inhititor of the activity of poly (ADP-ribose) polymerase, in a rodent model of lung injury[J]. Biochem Pharmacol, 2002, 63(2):293-304.
[13] 蔡 莉,王娅兰,林 晓. PARP 抑制与小鼠结肠癌 CT26 细胞生长活性的关系[J].重庆医科大学学报,2008,33(2):136-139.
[14] Wu Xiaopeng , Zeng Hu , Zhang Xianming , et al. Phosphatase of Regenerating Liver-3 Promotes Motility and Metastasis of Mouse Melanoma Cells [J] .American Journal of Pathology, 2004, 164(6):2039–2045.
[15] Hao LX, Wang YL, Cai L, et al. Inhibitory effect of 5-aminoisoquinolinone on PARP activity in colon carcinoma cell line HT-29[J]. Ai Zheng, 2007, 26(6):566-71.
[16] Tentori L, Lacal PM, Muzi A, et al. Poly(ADP-ribose) polymerase (PARP) inhibition or PARP-1 gene deletion reduces angiogenesis[J]. Eur J Cancer, 2007, 43(14):2124-33.
[17] Geng L, Ali S, Marshall J, et al. Fibronectin is chemotactic for CT 26 colon carcinoma cells: sub-lines selected for increased chemotaxis to fibronectin display decreased tumorigenicity and lung colonization [J] .Clin. Exp. Metastasis, 1998, 16(8):683–691.
[18] Wang J, Manning B, Wu Q, et al. Endotoxin / Lipopolysaccharide Activates NF-κB and Enhances Tumor Cell Adhesion and Invasion Through a β1 Integrin-Dependent Mechanism[J].The Journal of Immunology, 2003, 170(2): 795–804.
[19] Andela VB, Schwarz EM, Puzas JE, et al. Tumor Metastasis and the Reciprocal Regulation of Prometastatic and Antimetastatic Factors by Nuclear Factor kB.[J]. Cancer Res, 2000, 60(1):6557-6562.
[20] Maria E. Marin-Castan,Sharon J, et al. Regulation of Estrogen Receptors and MMP-2 Expression by Estrogens in Human Retinal Pigment Epithelium[J]. Investigative Ophthalmology & Visual Science, 2003, 44(1):50-59.
[21] Veres B, Radnai B, Gallyas F, et al. Regulation of Kinase Cascades and Transcription Factors by a Poly(ADP-Ribose) Polymerase-1 Inhibitor, 4-Hydroxyquinazoline, in Lipopolysaccharide-Induced Inflammation in Mice[J]. JPET, 2004, 310(1):247-255.
[1] Virág L and Szabó C. The therapeutic potential of poly(ADP-ribose) polymerase inhibitors[J]. Pharmacol Rev 2002; 54:375–429.
[2] Ruf A, Me′nissier de Murcia J, de Murcia G, and Schulz GE. Structure of the catalytic fragment of poly(ADP-ribose) polymerase from chicken[J]. Proc Natl Acad Sci USA 1996; 93:7481–7485.
[3] Davidovic L, Vodenicharov M, Affar EB, and Poirier GG. Importance of poly(ADP-ribose) glycohydrolase in the control of poly(ADP-ribose) metabolism[J]. Exp Cell Res 2001; 268:7–13.
[4] Orrenius S, Zhivotovsky B, and Nicotera P. Regulation of cell death: the calcium-apoptosis link[J]. Nat Rev Mol Cell Bio 2004; 4:552–565.
[5] Germain M, Affar EB, D’Amours D, Dixit VM, Salvesen GS, and Poirier GG. Cleavage of automodified poly(ADP-ribose) polymerase during apoptosis. Evidence for involvement of caspase-7[J]. J Biol Chem 1999; 274:28379–28384.
[6] Kim JW, Kim K, Kang K, and Joe CO. Inhibition of homodimerization of poly(ADP-ribose) polymerase by its C-terminal cleavage products produced during apoptosis[J]. J Biol Chem 2000; 275:8121–8125.
[7] Green DR and Reed JC. Mitochondria and apoptosis[J]. Science (Wash DC) 1998; 281:1309–1312.
[8] Ha HC, Snyder SH. Poly(ADP-ribose) polymerase is a mediator of necrotic cell death by ATP depletion[J]. Proc Natl Acad Sci U S A. 1999; 96:13978 –13982.
[9] Yu SW, Wang H, Poitras MF, Coombs C, Bowers WJ, Federoff HJ, Poirier GG, Dawson TM, Dawson VL. Mediation of poly(ADP-ribose) polymerase-1-dependent cell death by apoptosis-inducing factor[J]. Science. 2002;297:259 –263.
[10] Hassa PO, Hottiger MO. The functional role of poly(ADPribose) polymerase 1 as novel coactivator of NF-kappaB in inflammatory disorders[J]. Cell Mol Life Sci. 2002;59:1534 –1553.
[11] Sharma SS, Kumar A and Kaundal RK. Protective effects of 4-amino1,8-napthalimide, a poly (ADP-ribose) polymerase inhibitor in experimental diabetic neuropathy[J]. Life Sci, 2008; 82(11-12): 570-6.
[12] Adaikalakoteswari A, Rema M, Mohan V, et al. Oxidative DNA damage and augmentation of poly(ADP-ribose) polymerase/nuclear factor-kappa B signaling in patients with type 2 diabetes and microangiopathy[J]. Int J Biochem Cell Biol, 2007; 39(9): 1673-84.
[13] von Lukowicz T, Hassa PO, Lohmann C, et al. PARP1 is required for adhesion molecule expression in atherogenesis[J]. Cardiovasc Res. 2008; 78(1):158-66.
[14] Oumouna-Benachour K, Hans CP, Suzuki Y, et al. Poly(ADP-ribose) polymerase inhibition reduces atherosclerotic plaque size and promotes factors of plaque stability in apolipoprotein E-deficient mice: effects on macrophage recruitment, nuclear factor-kappaB nuclear translocation, and foam cell death[J]. Circulation. 2007; 115(18):2442-50.
[15] Gonzalez-Rey E, Martínez-Romero R, O'Valle F, et al. Therapeutic Effect of a Poly(ADP-Ribose) Polymerase-1 Inhibitor on Experimental Arthritis byDownregulating Inflammation and Th1 Response[J]. PLoS ONE. 2007; 2(10):e1071.
[16] Su CF, Liu DD, Kao SJ, et al. Nicotinamide abrogates acute lung injury caused by ischaemia/reperfusion[J]. Eur Respir J. 2007;30(2):199-204.
[17] Kovacs K, Toth A, Deres P, et al. Critical role of PI3-kinase/Akt activation in the PARP inhibitor induced heart function recovery during ischemia-reperfusion[J]. Biochem Pharmacol. 2006; 71(4):441-52.
[18] Zheng L, Gong B, Hatala DA, et al. Retinal ischemia and reperfusion causes capillary degeneration: similarities to diabetes[J]. Invest Ophthalmol Vis Sci. 2007; 48(1):361-7.
[19] Di Paola R, Mazzon E, Muià C, et al. 5-Aminoisoquinolin-1(2H)-one, a water-soluble poly (ADP-ribose) polymerase (PARP) inhibitor reduces the evolution of experimental periodontitis in rats[J]. J Clin Periodontol. 2007; 34(2):95-102.
[20] Sánchez-Fidalgo S, Villegas I, Martín A, et al. PARP inhibition reduces acute colonic inflammation in rats[J]. Eur J Pharmacol. 2007; 563(1-3):216-23.
[21] Mazzon E, Genovese T, Di Paola R, et al. Effects of 3-aminobenzamide, an inhibitor of poly (ADP-ribose) polymerase, in a mouse model of acute pancreatitis induced by cerulein[J]. Eur J Pharmacol. 2006; 549(1-3):149-56.
[2] Sharma SS, Kumar A and Kaundal RK. Protective effects of 4-amino1,8-napthalimide, a poly (ADP-ribose) polymerase inhibitor in experimental diabetic neuropathy[J]. Life Sci, 2008; 82(11-12): 570-6.
[3] Adaikalakoteswari A, Rema M, Mohan V, et al. Oxidative DNA damage and augmentation of poly(ADP-ribose) polymerase/nuclear factor-kappa B signaling in patients with type 2 diabetes and microangiopathy[J]. Int J Biochem Cell Biol, 2007; 39(9): 1673-84.
[4] von Lukowicz T, Hassa PO, Lohmann C, et al. PARP1 is required for adhesion molecule expression in atherogenesis[J]. Cardiovasc Res. 2008; 78(1):158-66.
[5] Oumouna-Benachour K, Hans CP, Suzuki Y, et al. Poly(ADP-ribose) polymerase inhibition reduces atherosclerotic plaque size and promotes factors of plaque stability in apolipoprotein E-deficient mice: effects on macrophage recruitment, nuclear factor-kappaB nuclear translocation, and foam cell death[J]. Circulation. 2007; 115(18):2442-50.
[6] Kovacs K, Toth A, Deres P, et al. Critical role of PI3-kinase/Akt activation in the PARP inhibitor induced heart function recovery during ischemia-reperfusion[J]. Biochem Pharmacol. 2006; 71(4):441-52.
[7] Tentori L, Leonetti C, Scarsella M, et al. Inhibition of poly(ADP-ribose) polymerase prevents irinotecan-induced intestinal damage and enhances irinotecan / temozolomide efficacy against colon carcinoma [J]. The FASEB Journal, 2006, 20(10):1709-1711.
[8] Albert JM, Cao C, Kim KW, et al. Inhibition of Poly(ADP-Ribose) Polymerase Enhances Cell Death and Improves Tumor Growth Delay in Irradiated Lung Cancer Models [J]. Clinical Cancer Research, 2007, 13(10): 3033-3042.
[9] 郝兰香,王娅兰,李圆圆。大肠癌 PARP 表达与 P-selectin 和 ICAM-1 表达的相关性 [J].基础医学与临床,2006,26(8):882-887。
[10] Rajesh M, Mukhopadhyay P, Godlewski G, et al. Poly(ADP-ribose)polymeraseinhibition decreases angiogenesis[J]. Biochemical and Biophysical Research Communications, 2006, 350(4): 1056–1062.
[11] Gonzalez-Rey E, Martínez-Romero R, O'Valle F, et al. Therapeutic Effect of a Poly(ADP-Ribose) Polymerase-1 Inhibitor on Experimental Arthritis by Downregulating Inflammation and Th1 Response[J]. PLoS ONE. 2007; 2(10):e1071.
[12] Cuzzocrea S, McDonald MC, Mazzon E, et al. Effects of 5-aminoisoquinolione, a water-soluble, potent inhititor of the activity of poly (ADP-ribose) polymerase, in a rodent model of lung injury[J]. Biochem Pharmacol, 2002, 63(2):293-304.
[13] 蔡 莉,王娅兰,林 晓. PARP 抑制与小鼠结肠癌 CT26 细胞生长活性的关系[J].重庆医科大学学报,2008,33(2):136-139.
[14] Wu Xiaopeng , Zeng Hu , Zhang Xianming , et al. Phosphatase of Regenerating Liver-3 Promotes Motility and Metastasis of Mouse Melanoma Cells [J] .American Journal of Pathology, 2004, 164(6):2039–2045.
[15] Hao LX, Wang YL, Cai L, et al. Inhibitory effect of 5-aminoisoquinolinone on PARP activity in colon carcinoma cell line HT-29[J]. Ai Zheng, 2007, 26(6):566-71.
[16] Tentori L, Lacal PM, Muzi A, et al. Poly(ADP-ribose) polymerase (PARP) inhibition or PARP-1 gene deletion reduces angiogenesis[J]. Eur J Cancer, 2007, 43(14):2124-33.
[17] Geng L, Ali S, Marshall J, et al. Fibronectin is chemotactic for CT 26 colon carcinoma cells: sub-lines selected for increased chemotaxis to fibronectin display decreased tumorigenicity and lung colonization [J] .Clin. Exp. Metastasis, 1998, 16(8):683–691.
[18] Wang J, Manning B, Wu Q, et al. Endotoxin / Lipopolysaccharide Activates NF-κB and Enhances Tumor Cell Adhesion and Invasion Through a β1 Integrin-Dependent Mechanism[J].The Journal of Immunology, 2003, 170(2): 795–804.
[19] Andela VB, Schwarz EM, Puzas JE, et al. Tumor Metastasis and the Reciprocal Regulation of Prometastatic and Antimetastatic Factors by Nuclear Factor kB.[J]. Cancer Res, 2000, 60(1):6557-6562.
[20] Maria E. Marin-Castan,Sharon J, et al. Regulation of Estrogen Receptors and MMP-2 Expression by Estrogens in Human Retinal Pigment Epithelium[J]. Investigative Ophthalmology & Visual Science, 2003, 44(1):50-59.
[21] Veres B, Radnai B, Gallyas F, et al. Regulation of Kinase Cascades and Transcription Factors by a Poly(ADP-Ribose) Polymerase-1 Inhibitor, 4-Hydroxyquinazoline, in Lipopolysaccharide-Induced Inflammation in Mice[J]. JPET, 2004, 310(1):247-255.
[1] Virág L and Szabó C. The therapeutic potential of poly(ADP-ribose) polymerase inhibitors[J]. Pharmacol Rev 2002; 54:375–429.
[2] Ruf A, Me′nissier de Murcia J, de Murcia G, and Schulz GE. Structure of the catalytic fragment of poly(ADP-ribose) polymerase from chicken[J]. Proc Natl Acad Sci USA 1996; 93:7481–7485.
[3] Davidovic L, Vodenicharov M, Affar EB, and Poirier GG. Importance of poly(ADP-ribose) glycohydrolase in the control of poly(ADP-ribose) metabolism[J]. Exp Cell Res 2001; 268:7–13.
[4] Orrenius S, Zhivotovsky B, and Nicotera P. Regulation of cell death: the calcium-apoptosis link[J]. Nat Rev Mol Cell Bio 2004; 4:552–565.
[5] Germain M, Affar EB, D’Amours D, Dixit VM, Salvesen GS, and Poirier GG. Cleavage of automodified poly(ADP-ribose) polymerase during apoptosis. Evidence for involvement of caspase-7[J]. J Biol Chem 1999; 274:28379–28384.
[6] Kim JW, Kim K, Kang K, and Joe CO. Inhibition of homodimerization of poly(ADP-ribose) polymerase by its C-terminal cleavage products produced during apoptosis[J]. J Biol Chem 2000; 275:8121–8125.
[7] Green DR and Reed JC. Mitochondria and apoptosis[J]. Science (Wash DC) 1998; 281:1309–1312.
[8] Ha HC, Snyder SH. Poly(ADP-ribose) polymerase is a mediator of necrotic cell death by ATP depletion[J]. Proc Natl Acad Sci U S A. 1999; 96:13978 –13982.
[9] Yu SW, Wang H, Poitras MF, Coombs C, Bowers WJ, Federoff HJ, Poirier GG, Dawson TM, Dawson VL. Mediation of poly(ADP-ribose) polymerase-1-dependent cell death by apoptosis-inducing factor[J]. Science. 2002;297:259 –263.
[10] Hassa PO, Hottiger MO. The functional role of poly(ADPribose) polymerase 1 as novel coactivator of NF-kappaB in inflammatory disorders[J]. Cell Mol Life Sci. 2002;59:1534 –1553.
[11] Sharma SS, Kumar A and Kaundal RK. Protective effects of 4-amino1,8-napthalimide, a poly (ADP-ribose) polymerase inhibitor in experimental diabetic neuropathy[J]. Life Sci, 2008; 82(11-12): 570-6.
[12] Adaikalakoteswari A, Rema M, Mohan V, et al. Oxidative DNA damage and augmentation of poly(ADP-ribose) polymerase/nuclear factor-kappa B signaling in patients with type 2 diabetes and microangiopathy[J]. Int J Biochem Cell Biol, 2007; 39(9): 1673-84.
[13] von Lukowicz T, Hassa PO, Lohmann C, et al. PARP1 is required for adhesion molecule expression in atherogenesis[J]. Cardiovasc Res. 2008; 78(1):158-66.
[14] Oumouna-Benachour K, Hans CP, Suzuki Y, et al. Poly(ADP-ribose) polymerase inhibition reduces atherosclerotic plaque size and promotes factors of plaque stability in apolipoprotein E-deficient mice: effects on macrophage recruitment, nuclear factor-kappaB nuclear translocation, and foam cell death[J]. Circulation. 2007; 115(18):2442-50.
[15] Gonzalez-Rey E, Martínez-Romero R, O'Valle F, et al. Therapeutic Effect of a Poly(ADP-Ribose) Polymerase-1 Inhibitor on Experimental Arthritis byDownregulating Inflammation and Th1 Response[J]. PLoS ONE. 2007; 2(10):e1071.
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