Rousseau-Plasse A, Wdzieczak-Bakala J, Lenfant M, Ezan E, Genet R, Robinson S, Briscoe T, Melville J, Riches A
Institut de Chimie des Substances Naturelles, Centre National de la Recherche Scientifique, Gif-sur-Yvette, France.
Exp Hematol. 1998 Oct;26(11):1074-9.
The hemoregulatory peptide N-Acetyl-Ser-Asp-Lys-Pro (AcSDKP) has been shown in vivo to inhibit the cycling of murine hematopoietic stem cells triggered into S-phase by either cytotoxic drug administration or irradiation. This property, further confirmed using in vitro models, demonstrates that the peptide has an in vivo protective effect on the hematopoietic system. AcSDKP has been shown to be a physiological substrate of angiotensin I-converting enzyme (ACE), which catabolizes the peptide through a dipeptidasic activity. Thus, oral administration of ACE inhibitor to humans has led to an increase in the plasma AcSDKP concentration. In the present paper, we report on the in vivo effect of lisinopril, an ACE inhibitor, on the proliferative status of murine hematopoietic stem cells triggered into S-phase by irradiation. Administration of lisinopril (10 mg/kg) 1 hour after irradiation led to a 90 to 100% inhibition of murine plasma ACE activity as observed during the first 4 hours postirradiation. This inhibition was correlated with a 600% increase in the endogenous plasma AcSDKP level and a total suppression at 24 hours of entry of the hematopoietic stem cell into the cell cycle. We discuss the possible role of ACE in the regulation of hematopoietic stem cell proliferation through control of the AcSDKP concentration.
血液调节肽N-乙酰基-丝氨酸-天冬氨酸-赖氨酸-脯氨酸（AcSDKP）已在体内被证实，它能够抑制因给予细胞毒性药物或辐射而被触发进入S期的小鼠造血干细胞的循环。利用体外模型进一步证实的这一特性表明，该肽对造血系统具有体内保护作用。AcSDKP已被证明是血管紧张素I转换酶（ACE）的一种生理底物，ACE通过二肽酶活性分解该肽。因此，对人类口服ACE抑制剂会导致血浆AcSDKP浓度升高。在本文中，我们报告了ACE抑制剂赖诺普利对因辐射而被触发进入S期的小鼠造血干细胞增殖状态的体内作用。辐射后1小时给予赖诺普利（10毫克/千克），在辐射后的前4小时观察到小鼠血浆ACE活性受到90%至100%的抑制。这种抑制与内源性血浆AcSDKP水平增加600%以及造血干细胞在24小时时进入细胞周期的完全抑制相关。我们讨论了ACE通过控制AcSDKP浓度在调节造血干细胞增殖中可能发挥的作用。
