Kim Y M, Bergonia H A, Müller C, Pitt B R, Watkins W D, Lancaster J R
Department of Surgery, University of Pittsburgh School of Medicine, Pennsylvania 15261.
J Biol Chem. 1995 Mar 17;270(11):5710-3. doi: 10.1074/jbc.270.11.5710.
We report here that, like nonheme iron, protein-bound intracellular heme iron is also a target for destruction by endogenously produced nitric oxide (NO). In isolated rat hepatocytes NO synthesis results in substantial (approximately 60%) and comparable loss of catalase and cytochrome P450 as well as total microsomal heme, and decreased heme synthetic (delta-aminolevulinate synthetase and ferrochelatase) and increased degradative (heme oxygenase) enzymatic activities. The effect is reversible, and intact cytochrome P450 apoproteins are still present, as judged by heme reconstitution of isolated microsomes. The effects on delta-aminolevulinate synthetase and heme oxygenase are likely to be secondary to heme liberation, while the effects on ferrochelatase appear to be a direct effect of NO, perhaps destruction of its nonheme iron-sulfur center.
我们在此报告，与非血红素铁一样，蛋白质结合的细胞内血红素铁也是内源性产生的一氧化氮（NO）的破坏目标。在分离的大鼠肝细胞中，NO合成导致过氧化氢酶和细胞色素P450以及总微粒体血红素大量（约60%）且相当程度的损失，同时血红素合成酶（δ-氨基乙酰丙酸合成酶和亚铁螯合酶）活性降低，降解酶（血红素加氧酶）活性增加。这种作用是可逆的，通过分离微粒体的血红素重建判断，完整的细胞色素P450脱辅基蛋白仍然存在。对δ-氨基乙酰丙酸合成酶和血红素加氧酶的影响可能继发于血红素的释放，而对亚铁螯合酶的影响似乎是NO的直接作用，可能是其非血红素铁硫中心被破坏。
