Modified cell-permeable JNK inhibitors efficiently prevents islet apoptosis and improves the outcome of islet transplantation.
Modified cell-permeable JNK inhibitors efficiently prevents islet apoptosis and improves the outcome of islet transplantation.
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DOI：
10.1038/s41598-018-29481-9
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发表时间：
2018-07-23
影响因子：
4.6
通讯作者：
Watanabe M
中科院分区：
文献类型：
--
作者：
Noguchi H;Miyagi-Shiohira C;Nakashima Y;Ebi N;Hamada E;Tamaki Y;Kuwae K;Kobayashi N;Saitoh I;Watanabe M
我们之前报道过，JNK 抑制肽 (11R-JNKI) 治疗可防止胰岛细胞凋亡并增强体内胰岛功能。在本研究中，我们探索了更有效的 JNK 抑制剂。研究了 11R-JNKI 中五种缺失肽对 JNK 活性的抑制。其中一种肽 8R-sJNKI(-9) 可显着阻止 JNK 激活。在1μM浓度下，8R-sJNKI(-9)对JNK活性的抑制作用与10μM 11R-JNKI相似，并且10μM 8R-sJNKI(-9)对JNK活性的抑制作用明显大于10μM 11R-JNK对JNK活性的抑制作用。为了评价8R-sJNKI(-9)的效果，用1μM的8R-sJNKI(-9)或8R突变体sJNKI(-9)(8R-mJNKI(-9))培养猪胰岛。培养1天后，8R-sJNKI(-9)处理组的胰岛数量显着高于8R-mJNKI(-9)处理组。胰岛移植后，链脲佐菌素诱导的糖尿病小鼠中，8R-sJNKI(-9)组中有58.3%的小鼠血糖水平达到正常血糖范围，而8R-mJNKI(-9)治疗组中只有0%的小鼠血糖水平达到正常血糖范围。这些数据表明8R-sJNKI(-9)抑制胰岛细胞凋亡并改善胰岛功能。
We previously reported that treatment with a JNK inhibitory peptide (11R-JNKI) prevents islet apoptosis and enhances the islet function in vivo. In the present study, we explored more efficient JNK inhibitors. The inhibition of the JNK activity by five types of deletion peptides in 11R-JNKI was investigated. One of the peptides, 8R-sJNKI(-9), significantly prevented JNK activation. At a concentration of 1 µM, 8R-sJNKI(-9) inhibited JNK activity similarly to 10 µM 11R-JNKI and the inhibition of the JNK activity by 10 µM 8R-sJNKI(-9) was significantly greater than that by 10 µM 11R-JNK. To evaluate the effects of 8R-sJNKI(-9), porcine islets were cultured with 1 µM of 8R-sJNKI(-9) or 8R-mutant sJNKI(-9) (8R-mJNKI(-9)). After 1 day of culture, the numbers of islets in the 8R-sJNKI(-9)-treated group was significantly higher than that in the 8R-mJNKI(-9)-treated group. After islet transplantation, the blood glucose levels reached the normoglycemic range in 58.3% of streptozotocin-induced diabetic mice in the 8R-sJNKI(-9) group and 0% of the mice in the 8R-mJNKI(-9)-treated group. These data suggest that 8R-sJNKI(-9) inhibits islet apoptosis and improves islet function.
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影响因子：
3.3
作者：
Noguchi, Hirofumi;Ueda, Michiko;Matsumoto, Shinichi
通讯作者：
Matsumoto, Shinichi
影响因子：
7.7
作者：
Davalli, AM;Scaglia, L;Weir, GC
通讯作者：
Weir, GC
影响因子：
8.2
作者：
Noguchi, H.;Nakai, Y.;Matsumoto, S.
通讯作者：
Matsumoto, S.
影响因子：
4.8
作者：
Kaneto, H;Xu, G;Weir, GC
通讯作者：
Weir, GC
影响因子：
7.7
作者：
RICORDI, C;LACY, PE;SCHARP, DW
通讯作者：
SCHARP, DW