PARP-1 Modulates Amyloid Beta Peptide-Induced Neuronal Damage

被引：59

作者：

Martire, Sara ^{[1
]}

Fuso, Andrea ^{[2
]}

Rotili, Dante ^{[3
]}

Tempera, Italo ^{[4
]}

Giordano, Cesare ^{[3
]}

De Zottis, Ivana ^{[1
]}

Muzi, Alessia ^{[5
]}

Vernole, Patrizia ^{[6
]}

Graziani, Grazia ^{[5
]}

Lococo, Emanuela ^{[7
]}

Faraldi, Martina ^{[1
]}

Maras, Bruno ^{[1
]}

Scarpa, Sigfrido ^{[8
]}

Mosca, Luciana ^{[1
]}

d'Erme, Maria ^{[1
,9
]}

机构：

[1] Sapienza Univ, Dept Biochem Sci, Rome, Italy

[2] Sapienza Univ, Dept Psychol Sec Neurosci, Rome, Italy

[3] Sapienza Univ, Dept Pharmaceut Studies, Rome, Italy

[4] Temple Univ, Fels Inst Canc Res & Mol Biol, Philadelphia, PA USA

[5] Univ Roma Tor Vergata, Dept Neurosci, Rome, Italy

[6] Univ Roma Tor Vergata, Dept Publ Hlth & Cell Biol, Rome, Italy

[7] Sapienza Univ, Dept Expt Med, Rome, Italy

[8] Sapienza Univ, Dept Surg P Valdoni, Rome, Italy

[9] Sapienza Univ, Fdn Cenci Bolognetti, Inst Pasteur, Rome, Italy

来源：

PLOS ONE | 2013年 / 8卷 / 09期

关键词：

NF-KAPPA-B; POLY(ADP-RIBOSE) POLYMERASE-1; OXIDATIVE STRESS; A-BETA; DNA-BINDING; SIGNAL-TRANSDUCTION; CELL-DEATH; ACTIVATION; BRAIN; TARGET;

D O I：

10.1371/journal.pone.0072169

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Amyloid beta peptide (A beta) causes neurodegeneration by several mechanisms including oxidative stress, which is known to induce DNA damage with the consequent activation of poly (ADP-ribose) polymerase (PARP-1). To elucidate the role of PARP-1 in the neurodegenerative process, SH-SY5Y neuroblastoma cells were treated with A beta(25-35) fragment in the presence or absence of MC2050, a new PARP-1 inhibitor. A beta(25-35) induces an enhancement of PARP activity which is prevented by cell pre-treatment with MC2050. These data were confirmed by measuring PARP-1 activity in CHO cells transfected with amylod precursor protein and in vivo in brains specimens of TgCRND8 transgenic mice overproducing the amyloid peptide. Following A beta(25-35) exposure a significant increase in intracellular ROS was observed. These data were supported by the finding that A beta(25-35) induces DNA damage which in turn activates PARP-1. Challenge with A beta(25-35) is also able to activate NF-kB via PARP-1, as demonstrated by NF-kB impairment upon MC2050 treatment. Moreover, A beta(25-35) via PARP-1 induces a significant increase in the p53 protein level and a parallel decrease in the anti-apoptotic Bcl-2 protein. These overall data support the hypothesis of PARP-1 involvment in cellular responses induced by A beta and hence a possible rationale for the implication of PARP-1 in neurodegeneration is discussed.

引用

页数：10

共 67 条

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