DPQ is a potent, blood-brain barrier-permeable poly(ADP-ribose) polymerase-1 (PARP-1) selective inhibitor used to study DNA damage repair and related cellular processes[1-2]. DPQ can be applied to investigate inflammatory responses and cell death mechanisms in acute lung injury, myocardial ischemia-reperfusion injury, and neurodegenerative diseases, demonstrating neuroprotective and cardioprotective effects[3-4].
In vitro, pretreatment of non-small cell lung cancer cells (A549 and H1299) with DPQ (1μM) for 4 hours, followed by carbon ion irradiation (0.5–2Gy) for 24 hours, significantly inhibited cell migration, wound healing capacity, and the activity and expression of matrix metalloproteinases (MMP-2 and MMP-9)[5]. Pretreatment of HeLa cells with DPQ (20–150μM) for 1 hour, followed by stimulation with PMA (50nM) for 3 hours, significantly suppressed the upregulation of histamine H1 receptor (H1R) gene expression and reduced H1R promoter activity[6].
In vivo, pretreatment of C57BL/6 mice with DPQ (15mg/kg) 24 hours before renal ischemia for 45 minutes/reperfusion for 6 hours reduced ischemia-reperfusion-related pathological damage, such as acute tubular necrosis (ATN), tubular cell vacuolization, and brush border loss, by inhibiting PARP-1 overactivation, while also ameliorating tubular epithelial cell shedding and cast formation[7]. Pretreatment of C57BL/6 mice with LPS (7.5mg/kg) for 30 minutes, followed by intraperitoneal injection of DPQ (10μg/kg) for 6 hours, significantly inhibited neutrophil infiltration and myeloperoxidase (MPO) activity in lung tissue, while reducing the mRNA expression levels of pro-inflammatory factors such as TNF-α, IL-1β, and IL-6[8].
References:
[1] Meli E, Pangallo M, Picca R, et al. Differential role of poly(ADP-ribose) polymerase-1in apoptotic and necrotic neuronal death induced by mild or intense NMDA exposure in vitro. Mol Cell Neurosci. 2004 Jan;25(1):172-80.
[2] Wang J, Hao L, Wang Y, et al. Inhibition of poly (ADP-ribose) polymerase and inducible nitric oxide synthase protects against ischemic myocardial damage by reduction of apoptosis. Mol Med Rep. 2015 Mar;11(3):1768-76.
[3] Czapski GA, Cakala M, Kopczuk D, et al. Effect of poly(ADP-ribose) polymerase inhibitors on oxidative stress evoked hydroxyl radical level and macromolecules oxidation in cell free system of rat brain cortex. Neurosci Lett. 2004 Feb 6;356(1):45-8.
[4] Suh SW, Aoyama K, Alano CC, et al. Zinc inhibits astrocyte glutamate uptake by activation of poly(ADP-ribose) polymerase-1. Mol Med. 2007 Jul-Aug;13(7-8):344-9.
[5] Chowdhury P, Dey P, Ghosh S, et al. Reduction of metastatic potential by inhibiting EGFR/Akt/p38/ERK signaling pathway and epithelial-mesenchymal transition after carbon ion exposure is potentiated by PARP-1 inhibition in non-small-cell lung cancer. BMC Cancer. 2019 Aug 22;19(1):829.
[6] Mizuguchi H, Terao T, Kitai M, et al. Involvement of protein kinase Cdelta/extracellular signal-regulated kinase/poly(ADP-ribose) polymerase-1 (PARP-1) signaling pathway in histamine-induced up-regulation of histamine H1 receptor gene expression in HeLa cells. J Biol Chem. 2011 Sep 2;286(35):30542-30551.
[7] del Moral RM, Gómez-Morales M, Hernández-Cortés P, et al. PARP inhibition attenuates histopathological lesion in ischemia/reperfusion renal mouse model after cold prolonged ischemia. ScientificWorldJournal. 2013 Nov 11;2013:486574.
[8] Wang G, Huang X, Li Y, et al. PARP-1 inhibitor, DPQ, attenuates LPS-induced acute lung injury through inhibiting NF-κB-mediated inflammatory response. PLoS One. 2013 Nov 21;8(11):e79757.
DPQ是一种有效的、可穿透血脑屏障的聚腺苷二磷酸核糖聚合酶-1（PARP-1）选择性抑制剂，用于研究DNA损伤修复及相关细胞过程[1-2]。DPQ可用于研究急性肺损伤、心肌缺血再灌注损伤以及神经退行性疾病中的炎症反应与细胞死亡机制，并表现出神经保护和心脏保护作用[3-4]。
在体外，DPQ（1μM）预处理非小细胞肺癌细胞（A549和H1299）4小时，随后以碳离子（0.5–2Gy）照射24小时，DPQ显著抑制细胞迁移、伤口愈合能力及基质金属蛋白酶（MMP-2和MMP-9）的活性与表达[5]。DPQ（20–150μM）预处理HeLa细胞1小时，随后以PMA（50nM）刺激3小时，DPQ显著抑制组胺H1受体（H1R）基因表达的上调，同时降低H1R启动子活性[6]。
在体内，DPQ（15mg/kg）预处理C57BL/6小鼠24小时，随后进行肾脏缺血45分钟/再灌注6小时，DPQ通过抑制PARP-1过度激活，减少急性肾小管坏死（ATN）、肾小管细胞空泡化及刷状缘丢失等缺血再灌注相关病理损伤，同时改善肾小管上皮细胞脱落和管型形成[7]。LPS（7.5mg/kg）预处理C57BL/6小鼠30分钟，随后以DPQ（10μg/kg）腹腔注射刺激6小时，DPQ显著抑制肺组织中中性粒细胞浸润及髓过氧化物酶（MPO）活性，同时降低TNF-α、IL-1β、IL-6等促炎因子的mRNA表达水平[8]。