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2015 ; 12
(3
): 4079-4088
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Protection of rat intestinal epithelial cells from ischemia/reperfusion injury by
(D-Ala2, D-Leu5)-enkephalin through inhibition of the MKK7-JNK signaling pathway
#MMPMID26126577
Wang Z
; Tang B
; Tang F
; Li Y
; Zhang G
; Zhong L
; Dong C
; He S
Mol Med Rep
2015[Sep]; 12
(3
): 4079-4088
PMID26126577
show ga
Previous studies have demonstrated that (D?Ala2, D?Leu5)?enkephalin (DADLE)
protects rats from hepatic ischemia/reperfusion (I/R) injury. In the present
study, DADLE was also observed to alleviate IR?induced intestinal epithelial cell
injury in rats by inhibiting mitogen?activated protein kinase kinase 7
(MKK7)?c?Jun N?terminal kinase (JNK) pathway signaling. To investigate the
protective effect of DADLE on hypoxia/reoxygenation injury in rat intestinal
epithelial cells, rat intestinal epithelial cells were treated with different
concentrations of DADLE, following which the cell survival rate was determined
using a tetrazolium (MTT) colorimetric assay, and apoptosis was determined using
flow cytometry. To confirm whether the protective effect of DADLE was due to its
effect on MKK7?JNK signaling, the phosphorylation levels of MKK7 and JNK were
analyzed using western blot analysis following treatment with different
concentrations of DADLE. The results demonstrated that, following treatment with
DADLE, the survival rate of the rat intestinal cells subjected to I/R?induced
injury increased significantly and the apoptotic rate decreased in a
concentration?dependent manner. In addition, the levels of phosphorylated MKK7
and JNK decreased in a concentration?dependent manner following treatment with
DADLE. Silencing the gene expression of MKK7 using small interfering RNA prior to
DADLE treatment resulted in a reduction in the protective effects of DADLE on the
rat intestinal epithelial cells subjected to I/R injury. Collectively, the
results of the present study demonstrated that the protective effects of DADLE in
I/R injury in rat intestinal cells occurred through inhibition of the MKK7?JNK
pathway.