1.The Effects of Angiotensin Converting Enzyme Inhibitors (ACE-I) on Human N-Acetyl-Seryl-Aspartyl-Lysyl-Proline (Ac-SDKP) Levels: A Systematic Review and Meta-Analysis.
Mnguni AT1, Engel ME1, Borkum MS1, Mayosi BM1. PLoS One. 2015 Dec 11;10(12):e0143338. doi: 10.1371/journal.pone.0143338. eCollection 2015.
BACKGROUND: Tuberculous pericardial effusion is a pro-fibrotic condition that is complicated by constrictive pericarditis in 4% to 8% of cases. N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) is a ubiquitous tetrapeptide with anti-fibrotic properties that is low in tuberculous pericardial effusion, thus providing a potential mechanism for the heightened fibrotic state. Angiotensin-converting enzyme inhibitors (ACE-I), which increase Ac-SDKP levels with anti-fibrotic effects in animal models, are candidate drugs for preventing constrictive pericarditis if they can be shown to have similar effects on Ac-SDKP and fibrosis in human tissues.
2.N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP): Potential target molecule in research of heart, kidney and brain.
Hrenak J, Paulis L, Simko F1. Curr Pharm Des. 2015;21(35):5135-43.
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.
3.[Inhibition effect of N-acetyl-seryl-aspartyl-lysyl-proline on myofibroblast differentiation by regulating acetylated tubulin α in silicotic rat model].
Li S1, Gao X1, Xu D1, Wang X1, Liu Y1, Zhang L1, Deng H1, Wei Z1, Tian J1, Xu H1, Yang F2. Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi. 2015 Nov;33(11):816-21.
OBJECTIVE: To explore the inhibition effect and mechanism of N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP)on myofibroblast differentiation via regulating acetylated tubulin α (Ac-Tub α)in vivo and in vitro.
4.Effects of thymosin β4 and its N-terminal fragment Ac-SDKP on TGF-β-treated human lung fibroblasts and in the mouse model of bleomycin-induced lung fibrosis.
Conte E1, Iemmolo M, Fruciano M, Fagone E, Gili E, Genovese T, Esposito E, Cuzzocrea S, Vancheri C. Expert Opin Biol Ther. 2015;15 Suppl 1:S211-21. doi: 10.1517/14712598.2015.1026804. Epub 2015 Jun 22.
Thymosin β4 (Tβ4) and its amino-terminal fragment comprising N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) have been reported to act as anti-inflammatory and anti-fibrotic agents in vitro and in vivo. In recent papers, we have shown that Tβ4 exerts a widely protective role in mice treated with bleomycin, and in particular, we have demonstrated its inhibitory effects on both inflammation and early fibrosis.
