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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Am+J+Physiol+Renal+Physiol
2016 ; 310
(10
): F1026-34
Nephropedia Template TP
gab.com Text
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English Wikipedia
The anti-inflammatory peptide Ac-SDKP is released from thymosin-?4 by renal
meprin-? and prolyl oligopeptidase
#MMPMID26962108
Kumar N
; Nakagawa P
; Janic B
; Romero CA
; Worou ME
; Monu SR
; Peterson EL
; Shaw J
; Valeriote F
; Ongeri EM
; Niyitegeka JM
; Rhaleb NE
; Carretero OA
Am J Physiol Renal Physiol
2016[May]; 310
(10
): F1026-34
PMID26962108
show ga
N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) is a natural tetrapeptide with
anti-inflammatory and antifibrotic properties. Previously, we have shown that
prolyl oligopeptidase (POP) is involved in the Ac-SDKP release from thymosin-?4
(T?4). However, POP can only hydrolyze peptides shorter than 30 amino acids, and
T?4 is 43 amino acids long. This indicates that before POP hydrolysis takes
place, T?4 is hydrolyzed by another peptidase that releases NH2-terminal
intermediate peptide(s) with fewer than 30 amino acids. Our peptidase database
search pointed out meprin-? metalloprotease as a potential candidate. Therefore,
we hypothesized that, prior to POP hydrolysis, T?4 is hydrolyzed by meprin-?. In
vitro, we found that the incubation of T?4 with both meprin-? and POP released
Ac-SDKP, whereas no Ac-SDKP was released when T?4 was incubated with either
meprin-? or POP alone. Incubation of T?4 with rat kidney homogenates
significantly released Ac-SDKP, which was blocked by the meprin-? inhibitor
actinonin. In addition, kidneys from meprin-? knockout (KO) mice showed
significantly lower basal Ac-SDKP amount, compared with wild-type mice. Kidney
homogenates from meprin-? KO mice failed to release Ac-SDKP from T?4. In vivo, we
observed that rats treated with the ACE inhibitor captopril increased plasma
concentrations of Ac-SDKP, which was inhibited by the coadministration of
actinonin (vehicle, 3.1 ± 0.2 nmol/l; captopril, 15.1 ± 0.7 nmol/l; captopril +
actinonin, 6.1 ± 0.3 nmol/l; P < 0.005). Similar results were obtained with
urinary Ac-SDKP after actinonin treatment. We conclude that release of Ac-SDKP
from T?4 is mediated by successive hydrolysis involving meprin-? and POP.