Lisinopril an angiotensin 1-converting enzyme inhibitor, prevents entry of murine haematopoietic stem cells into the cell cycle after irradiation in vivo

Andrew Clive Riches, A Rousseau-Plasse, J Wdzieczak-Bakala, M Lenfant, other 5

Research output: Contribution to journalArticlepeer-review

Abstract

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 prop erty, 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.

Original languageEnglish
Pages (from-to)1074-1079
Number of pages6
JournalExperimental Haematology
Volume26
Publication statusPublished - Oct 1998

Keywords

  • AcSDKP
  • angiotensin I-converting enzyme (ACE)
  • ACE inhibitor
  • stem cell
  • ASP-LYS-PRO
  • SYNTHETIC TETRAPEPTIDE ACSDKP
  • LONG-TERM CULTURE
  • BONE-MARROW
  • NEGATIVE REGULATOR
  • PROGENITOR CELLS
  • PROLIFERATION
  • PLASMA
  • MICE
  • SERASPENIDE

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