The anti-inflammatory peptide Ac-SDKP is released from thymosin β4 by renal meprin α and prolyl oligopeptidase.

The anti-inflammatory peptide Ac-SDKP is released from thymosin β4 by renal meprin α and prolyl oligopeptidase. Am J Physiol Renal Physiol. 2016 Mar 9;:ajprenal.00562.2015 Authors: Kumar N, Nakagawa P, Janic B, Romero CA, Worou ME, Monu SR, Peterson EL, Shaw J, Valeriote F, Ongeri EM, Niyitegeka JV, Rhaleb NE, Carretero OA Abstract N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) is a natural tetra-peptide with anti-inflammatory and anti-fibrotic properties. We have previously shown that prolyl-oligopeptidase (POP) is involved in the Ac-SDKP release from thymosin β4 (Tβ4). However, POP can only hydrolyze peptides shorter than 30 amino acids and Tβ4 is 43 amino acids long. This indicates that before POP hydrolysis takes place, Tβ4 is hydrolyzed by another peptidase that releases N-terminal intermediate peptide(s) less than 30 amino acids. Our peptidase database search pointed out meprin α metalloprotease as a potential candidate. Therefore, we hypothesized that prior to POP hydrolysis, Tβ4 is hydrolyzed by meprin α. In vitro, we found that the incubation of Tβ4 with both, meprin α and POP released Ac-SDKP, whereas no Ac-SDKP was released when Tβ4 was incubated with either meprin α or POP alone. Incubation of Tβ4 with rat kidney homogenates significantly released Ac-SDKP, which was blocked by meprin α inhibitor, actinonin. In addition, kidneys from meprin α knockout (KO) mice showed significantly lower basal Ac-SDKP amou...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research