Captopril inhibits in vitro and in vivo the proliferation of primitive haematopoietic cells induced into cell cycle by cytotoxic drug administration or irradiation but has no effect on myeloid leukaemia cell proliferation
Captopril inhibits in vitro and in vivo the proliferation of primitive haematopoietic cells induced into cell cycle by cytotoxic drug administration or irradiation but has no effect on myeloid leukaemia cell proliferation
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DOI：
10.1046/j.1365-2141.2000.02073.x
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发表时间：
2000-06-01
影响因子：
6.5
通讯作者：
Wdzieczak-Bakala, J
中科院分区：
文献类型：
--
作者：
Chisi, JE;Briscoe, CV;Wdzieczak-Bakala, J
血管紧张素I转换酶（ACE）参与乙酰-丝氨酸-天冬氨酸-赖氨酸-脯氨酸（AcSDKP）四肽的催化。由于AcSDKP是造血干细胞增殖的生理性抑制剂，我们研究了血管紧张素转换酶（ACE）的特异性抑制剂之一卡托普利对原始造血细胞增殖的体外和体内影响。从注射阿糖胞苷（100 mg/kg）的小鼠获得的再生骨髓细胞以及SA 2髓性白血病细胞与10（-6）M卡托普利体外孵育24小时。Captopril可显著降低S期高增殖潜能集落形成细胞（HPP-CFC-1）的比例，而对S期SA 2白血病集落形成细胞的比例无影响。当在2戈伊γ射线照射或阿糖胞苷（AraC）注射后1小时给予小鼠体内时，显示卡托普利（100 mg/kg）阻止由这些细胞毒性处理诱导的HPP-CFC-1进入S期。观察到的影响与ACE降解活性的降低和内源性AcSDKP水平的增加相关，无论是在卡托普利处理的骨髓细胞的上清液和处理的动物的血浆中。目前的研究结果表明，AcSDKP可能介导观察到在体外和体内的抑制作用，卡托普利对原始造血细胞增殖。
Angiotensin I-converting enzyme (ACE) has been shown to be involved in the catabolism of the tetrapeptide acetyl-Ser-Asp-Lys-Pro (AcSDKP). As AcSDKP is a physiological inhibitor of haematopoietic stem cell proliferation, we investigated the in vitro and in vivo effects of captopril, one of the specific inhibitors of ACE, on the proliferation of primitive haematopoietic cells. Regenerating bone marrow cells obtained From mice given one injection of cytosine arabinoside (100 mg/kg) as well as SA2 myeloid leukaemia cells were incubated in vitro for 24 h with 10(-6) M captopril. Captopril significantly reduced the proportion of high proliferative potential colony-forming cells (HPP-CFC-1) in S-phase, whereas it had no effect on the proportion of SA2 leukaemic colony-forming cells in S-phase. When given in vivo to mice 1 h after 2 Gy gamma-irradiation or cytosine arabinoside (AraC) injection, captopril (100 mg/kg) was shown to prevent HPP-CFC-1 entry into S-phase induced by these cytotoxic treatments. The observed effects correlated with a reduction in ACE degradative activity and an increase in the level of endogenous AcSDKP both in the supernatants of captopril-treated bone marrow cells and in plasma of treated animals. The present findings suggest that AcSDKP might mediate the observed in vitro and in vivo inhibitory effects of captopril on primitive haematopoietic cell proliferation.