The broad spectrum 2-oxoglutarate oxygenase inhibitor N-oxalylglycine is present in rhubarb and spinach leaves

The broad spectrum 2-oxoglutarate oxygenase inhibitor N-oxalylglycine is present in rhubarb and spinach leaves
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DOI:
10.1016/j.phytochem.2015.06.028
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发表时间:
2015-09-01
期刊:
影响因子:
3.8
通讯作者:
McCullagh, James S. O.
McCullagh, James S. O.
中科院分区:
生物学2区
文献类型:
--
作者:
Al-Qahtani, Khalid;Jabeen, Bushra;McCullagh, James S. O.

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2-氧代戊二酸(2 OG)和亚铁依赖性加氧酶参与从人类(其中一些是治疗靶标)到植物的生物体中的许多生物过程。这些酶由于其在缺氧信号传导和表观遗传调节中的作用而具有重要的生物医学意义。合成的N-草酰甘氨酸(NOG)是一种广谱的2 OG加氧酶抑制剂,目前广泛用于动物缺氧反应和染色质修饰的研究。我们报告了NOG作为一种天然产物存在于大黄(大黄)和菠菜(菠菜)叶中的鉴定;在土奇亚大肠杆菌或人胚肾细胞(HER 293 T)中未观察到NOG。这一发现提出了NOG通过抑制2 OG依赖性加氧酶在调节基因表达中发挥天然作用的可能性。这具有重要意义,因为2 OG依赖性加氧酶的三羧酸循环(TCA)中间体抑制在癌症研究中引起了主要兴趣。(C)2015爱思唯尔有限公司版权所有。
2-Oxoglutarate (2OG) and ferrous iron dependent oxygenases are involved in many biological processes in organisms ranging from humans (where some are therapeutic targets) to plants. These enzymes are of significant biomedicinal interest because of their roles in hypoxic signaling and epigenetic regulation. Synthetic N-oxalylglycine (NOG) has been identified as a broad-spectrum 2OG oxygenase inhibitor and is currently widely used in studies on the hypoxic response and chromatin modifications in animals. We report the identification of NOG as a natural product present in Rheum rhabarbarum (rhubarb) and Spinach oleracea (spinach) leaves; NOG was not observed in Escherchia coli or human embryonic kidney cells (HER 293T). The finding presents the possibility that NOG plays a natural role in regulating gene expression by inhibiting 2OG dependent oxygenases. This has significance because tricarboxylic acid cycle (TCA) intermediate inhibition of 2OG dependent oxygenases has attracted major interest in cancer research. (C) 2015 Elsevier Ltd. All rights reserved.