N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP): Potential target molecule in research of heart, kidney and brain

Current Pharmaceutical Design
Jaroslav HrenakFedor Simko

Abstract

N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) is a ubiquitous molecule generated in all mammalian tissues from the N-terminal sequence of thymosin β4 (Tβ4) by the action of propyl oligopeptidase. Ac-SDKP is an alternative substrate for angiotensin converting enzyme (ACE). There are several indications that Ac-SDKP may be protective in the cardiovascular system. First, the level of Ac- SDKP in plasma and tissues is reduced in some cardiovascular pathologies such as hypertension. Second, an administration of Ac-SDKP to rodents attenuates inflammation, cell differentiation, proliferation, and migration resulting in a reduction of fibrosis in the heart, vessels and kidneys in conditions of their disorders. Third, the treatment with ACE-inhibitors is associated with a reduced degradation and hence increased levels of Ac-SDKP, while a simultaneous treatment with monoclonal antibodies against Ac- SDKP partly counteracts the benefit of ACE-inhibition. Since Ac-SDKP fails to reduce blood pressure and left ventricular hypertrophy (LVH), its potential structural benefit is obviously mediated by direct action on tissue in preventing or reversing excessive fibrosis. The protection by ACE-inhibition seems to be partly mediated by increased...Continue Reading

Citations

Jul 26, 2016·International Journal of Molecular Sciences·Jaroslav HrenakFedor Simko
Mar 12, 2019·Canadian Journal of Physiology and Pharmacology·Kamal M KassemNour-Eddine Rhaleb
Apr 6, 2018·International Journal of Molecular Medicine·Xianliang DaiChun Liang
Nov 1, 2020·International Journal of Molecular Sciences·Jaroslav Hrenak, Fedor Simko
May 6, 2021·International Journal of Molecular Sciences·Michaela AdamcovaFedor Simko
Jun 8, 2021·Frontiers in Cell and Developmental Biology·Roberta GiordoGianfranco Pintus

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