Ono Y, Watanabe M, Inoue Y, Ohmoto T, Akiyama K, Tsutsui K, Seki S
Department of Neurological Surgery, Okayama University Medical School, Japan.
Brain Res Dev Brain Res. 1995 May 26;86(1-2):1-6. doi: 10.1016/0165-3806(94)00212-i.
Expression of the mammalian major apurinic/apyrimidinic (AP) endonuclease (designated as APEX nuclease, or HAP1, APE or Ref-1 gene product) during mouse brain development was investigated by in situ and northern blot hybridizations. The enzyme is known to be a redox factor (Ref-1) stimulating DNA binding activity of AP-1 binding proteins such as Fos and Jun as well as a multifunctional DNA repair enzyme having 5' AP endonuclease, DNA 3' repair diesterase, 3'-5' exonuclease and DNA 3'-phosphatase activities. In the embryonic and postnatal development, APEX mRNA was expressed at high levels in the proliferative zone of various brain regions, with showing temporal and spatial changes. Its expression decreased in association with brain development to the basal expression level which was observed even in adulthood, with the exception of its expression in the hippocampal formation. The growth-dependent expression of APEX gene suggests that it has some roles on cell proliferation and/or differentiation in developmental brain. Its expression on the hippocampal formation became significant from postnatal day 7 and then increased. The pyramidal and granule cell layers expressed it at a higher level than most other brain regions at postnatal day 21. The developmental change of APEX gene expression was not necessarily associated with the changes of expression of c-fos and c-jun genes measured by northern blot hybridization. However, the present results suggested that APEX/Ref-1 gene product can interact with AP-1 binding proteins in brain, especially in the hippocampal formation, to regulate some brain functions by redox-activation.
通过原位杂交和Northern印迹杂交法，研究了哺乳动物主要脱嘌呤/脱嘧啶（AP）核酸内切酶（命名为APEX核酸酶，或HAP1、APE或Ref-1基因产物）在小鼠脑发育过程中的表达情况。已知该酶是一种氧化还原因子（Ref-1），可刺激AP-1结合蛋白（如Fos和Jun）的DNA结合活性，同时也是一种具有5' AP核酸内切酶、DNA 3'修复二酯酶、3'-5'核酸外切酶和DNA 3'-磷酸酶活性的多功能DNA修复酶。在胚胎期和出生后的发育过程中，APEX mRNA在各个脑区的增殖区高水平表达，并呈现出时空变化。随着脑发育，其表达下降至成年期仍可观察到的基础表达水平，但海马结构中的表达除外。APEX基因的生长依赖性表达表明，它在发育中的脑的细胞增殖和/或分化中发挥某些作用。其在海马结构中的表达从出生后第7天开始显著，随后增加。在出生后第21天，锥体细胞层和颗粒细胞层的表达水平高于大多数其他脑区。APEX基因表达的发育变化不一定与通过Northern印迹杂交法检测的c-fos和c-jun基因表达的变化相关。然而，目前的结果表明，APEX/Ref-1基因产物可在脑中，尤其是在海马结构中与AP-1结合蛋白相互作用，通过氧化还原激活来调节某些脑功能。
