Cable E E, Healey J F, Greene Y, Evans C O, Bonkovsky H L
Department of Biochemistry, Emory University School of Medicine, Atlanta, GA.
Biochim Biophys Acta. 1991 Nov 15;1080(3):245-51. doi: 10.1016/0167-4838(91)90009-o.
Relationships between activities of delta-aminolevulinate synthase and heme oxygenase, respectively the rate-limiting enzymes of heme biosynthesis and degradation, have been studied in chick embryo liver cell cultures following exposure of the cultures to glutethimide and iron, a combination known to produce a synergistic induction of both enzymes. In time-course experiments, synergistic induction of heme oxygenase activity by glutethimide and iron preceded that of delta-aminolevulinate synthase by 4 h. Effects of selective inhibitors of both heme synthesis and degradation have also been studied with respect to effects on delta-aminolevulinate synthase and heme oxygenase activities. The synergistic induction of heme oxygenase by glutethimide and iron appears to be dependent upon cellular heme synthesis because addition of inhibitors of heme biosynthesis, 4,6-dioxoheptanoic acid or N-methyl-mesoporphyrin abolishes this synergistic induction. Exposure of cultures to tin-mesoporphyrin, a potent inhibitor of heme oxygenase, prevented the synergistic induction of delta-aminolevulinate synthase produced by glutethimide and iron, or, when added after induction was already established, promptly halted any further induction. These results suggest that the level of activity of heme oxygenase can reciprocally modulate intracellular heme levels and thus activity of delta-aminolevulinate synthase.
在鸡胚肝细胞培养物中，研究了δ-氨基乙酰丙酸合酶和血红素加氧酶的活性之间的关系，这两种酶分别是血红素生物合成和降解的限速酶。在将培养物暴露于格鲁米特和铁（已知该组合会对这两种酶产生协同诱导作用）之后进行了相关研究。在时间进程实验中，格鲁米特和铁对血红素加氧酶活性的协同诱导比δ-氨基乙酰丙酸合酶提前4小时。还研究了血红素合成和降解的选择性抑制剂对δ-氨基乙酰丙酸合酶和血红素加氧酶活性的影响。格鲁米特和铁对血红素加氧酶的协同诱导似乎依赖于细胞血红素合成，因为添加血红素生物合成抑制剂4,6-二氧庚酸或N-甲基中卟啉可消除这种协同诱导作用。将培养物暴露于血红素加氧酶的强效抑制剂锡中卟啉，可阻止格鲁米特和铁对δ-氨基乙酰丙酸合酶的协同诱导，或者在诱导已经建立后添加时，可迅速停止任何进一步的诱导。这些结果表明，血红素加氧酶的活性水平可以相互调节细胞内血红素水平，从而调节δ-氨基乙酰丙酸合酶的活性。
