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, USA.
Adv Pharmacol. 1995;34:277-91. doi: 10.1016/s1054-3589(08)61092-3.
Figure 2 depicts a working hypothesis for these results. Activation of .NO synthesis results in nitrogen oxide-induced loss of protein-bound heme from CYP proteins, which remain relatively intact. This heme liberation results in a decrease in heme synthesis (decreased ALAS) and an increase in heme degradation (increased HO). In addition, .NO synthesis results in direct inhibition of ferrochelatase, which further contributes to inhibition of heme synthesis. There also appears to be a mechanism to repair or resynthesize CYP after .NO synthesis is inhibited. Finally, a result of this effect may be protection against cellular injury, since increased HO is an important response against cellular injury from a variety of insults.
图2描绘了这些结果的一个工作假说。一氧化氮（.NO）合成的激活导致一氧化氮诱导细胞色素P450（CYP）蛋白结合血红素的丢失，而CYP蛋白仍相对完整。这种血红素的释放导致血红素合成减少（δ-氨基-γ-酮戊酸合成酶（ALAS）降低）和血红素降解增加（血红素加氧酶（HO）增加）。此外，.NO合成导致亚铁螯合酶直接受到抑制，这进一步导致血红素合成受到抑制。在.NO合成被抑制后，似乎也存在一种修复或重新合成CYP的机制。最后，这种效应的一个结果可能是对细胞损伤的保护作用，因为HO增加是对各种损伤引起的细胞损伤的一种重要反应。
