N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP): Potential target molecule in research of heart, kidney and brain.
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 availability of Ac-SDKP. Thus, it is to suppose that harvesting the knowledge on the role of Ac-SDKP in cardiovascular physiology and pathology could deepen our insight into the mechanisms of action of the renin-angiotensin system (RAS) as well as agents interfering with this system. The exciting protective potential of Ac-SDKP suggests that this compound could be a focused drug target not only in animal experiments but also in the clinical cardio-pharmacologic research in the near future.
Jaroslav
J
Hrenak
Ludovit
L
Paulis
Department of Pathophysiology School of Medicine, Comenius University Sasinkova 4, 811 08 Bratislava Slovak Republic. fedor.simko@fmed.uniba.sk.
Fedor
F
Simko
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000503:physiopathology*; D002319:Cardiovascular System / Q000378:metabolism*; D006801:Humans; D007668:Kidney / Q000378:metabolism; D058990:Molecular Targeted Therapy; D009842:Oligopeptides / Q000378:metabolism*; D007703:Peptidyl-Dipeptidase A / Q000187:drug effects / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000502:physiology
D000806:Angiotensin-Converting Enzyme Inhibitors; D009842:Oligopeptides; D007703:Peptidyl-Dipeptidase A; C058504:goralatide