Baldassarro Vito A, Marchesini Alessandra, Giardino Luciana, Calzà Laura
Health Science and Technologies Interdepartmental Center for Industrial Research (HST-ICIR), University of Bologna, Italy; Department of Pharmacy and Biotechnology, University of Bologna, Italy.
IRET Foundation, Ozzano Emilia, Italy.
Stem Cell Res. 2017 Jul;22:54-60. doi: 10.1016/j.scr.2017.05.011. Epub 2017 May 30.
Poly (ADP-ribose) polymerase (PARP) family members are ubiquitously expressed and play a key role in cellular processes, including DNA repair and cell death/survival balance. Accordingly, PARP inhibition is an emerging pharmacological strategy for cancer and neurodegenerative diseases. Consistent evidences support the critical involvement of PARP family members in cell differentiation and phenotype maturation. In this study we used an oligodendrocyte precursor cells (OPCs) enriched system derived from fetal and adult brain to investigate the role of PARP in OPCs proliferation, survival, and differentiation. The PARP inhibitors PJ34, TIQ-A and Olaparib were used as pharmacological tools. The main results of the study are: (i) PARP mRNA expression and PARP activity are much higher in fetal than in adult-derived OPCs; (ii) the culture treatment with PARP inhibitors is cytotoxic for OPCs derived from fetal, but not from adult, brain; (iii) PARP inhibition reduces cell number, according to the inhibitory potency of the compounds; (iv) PARP inhibition effect on fetal OPCs is a slow process; (v) PARP inhibition impairs OPCs maturation into myelinating OL in fetal, but not in adult cultures, according to the inhibitory potency of the compounds. These results have implications for PARP-inhibition therapies for diseases and lesions of the central nervous system, in particular for neonatal hypoxic/ischemic encephalopathy.
聚（ADP - 核糖）聚合酶（PARP）家族成员在全身广泛表达，并在包括DNA修复和细胞死亡/存活平衡在内的细胞过程中发挥关键作用。因此，PARP抑制是一种新兴的针对癌症和神经退行性疾病的药理学策略。一致的证据支持PARP家族成员在细胞分化和表型成熟中起关键作用。在本研究中，我们使用了源自胎儿和成人脑的富含少突胶质前体细胞（OPC）的系统，来研究PARP在OPC增殖、存活和分化中的作用。PARP抑制剂PJ34、TIQ - A和奥拉帕尼被用作药理学工具。该研究的主要结果如下：（i）胎儿来源的OPC中PARP mRNA表达和PARP活性远高于成人来源的OPC；（ii）用PARP抑制剂进行培养处理对胎儿来源的OPC具有细胞毒性，但对成人脑来源的OPC无细胞毒性；（iii）根据化合物的抑制效力，PARP抑制会减少细胞数量；（iv）PARP对胎儿OPC的抑制作用是一个缓慢的过程；（v）根据化合物的抑制效力，PARP抑制会损害胎儿来源的OPC成熟为有髓鞘形成能力的少突胶质细胞（OL），但对成人培养物中的OPC无此作用。这些结果对中枢神经系统疾病和损伤的PARP抑制疗法具有启示意义，特别是对于新生儿缺氧缺血性脑病。
