Lee H S, Lee Y S, Kim H S, Choi J Y, Hassan H M, Chung M H
Department of Pharmacology, Seoul National University College of Medicine, Chongno-gu, Seoul, Korea.
Free Radic Biol Med. 1998 May;24(7-8):1193-201. doi: 10.1016/s0891-5849(97)00427-9.
We found previously that 8-hydroxyguanine (oh8Gua) endonuclease in E. coli is induced in response to oxidative stress in a fashion similar to the oxidative response of the Mn-superoxide dismutase (MnSOD). In this study, attempts were made to identify the genes involved in the co-regulation of E. coli endonuclease and MnSOD (sodA). oh8Gua nuclease is induced by molecular oxygen and a superoxide radical generator (paraquat) but not by H2O2, suggesting that the regulation of this endonuclease is dependent on SoxRS but independent of OxyR. This enzyme was induced by paraquat in all of the soxRS mutant strains used (soxR-, soxS- and soxRc), whereas glucose-6-phosphate dehydrogenase (a member of the soxRS regulon) showed the expected responses; therefore, this possibility was excluded. The presence of metal chelators in the growth medium caused the induction of this enzyme, and this induction was suppressed by the addition of Fe++. Consistent with this finding, this enzyme was expressed under anaerobiosis in all of the mutant strains of fnr in particular, as well as fur, arcA, and combinations thereof. These findings suggest that the oxidative regulation of oh8Gua endonuclease is under control of fnr, fur, and arcA, where fnr plays a predominant role. The multiple involvement of regulatory genes as well as co-regulation with antioxidant enzyme will enhance the efficiency of cellular growth and survival in the aerobic environment.
我们之前发现，大肠杆菌中的8-羟基鸟嘌呤（oh8Gua）内切酶在氧化应激反应中被诱导，其方式类似于锰超氧化物歧化酶（MnSOD）的氧化反应。在本研究中，我们试图鉴定参与大肠杆菌内切酶和MnSOD（sodA）共同调控的基因。oh8Gua核酸酶可被分子氧和超氧化物自由基产生剂（百草枯）诱导，但不能被H2O2诱导，这表明该内切酶的调控依赖于SoxRS，但不依赖于OxyR。在所使用的所有soxRS突变菌株（soxR-、soxS-和soxRc）中，该酶均被百草枯诱导，而葡萄糖-6-磷酸脱氢酶（soxRS调控子的成员之一）表现出预期的反应；因此，这种可能性被排除。生长培养基中金属螯合剂的存在导致该酶的诱导，而添加Fe++可抑制这种诱导。与此发现一致，该酶在厌氧条件下在所有fnr突变菌株中均有表达，特别是在fur、arcA及其组合的突变菌株中。这些发现表明，oh8Gua内切酶的氧化调控受fnr、fur和arcA的控制，其中fnr起主要作用。调控基因的多重参与以及与抗氧化酶的共同调控将提高细胞在有氧环境中的生长和存活效率。
