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低聚甘露糖醛酸通过抑制JNK激活和细胞凋亡，预防胰岛淀粉样多肽在RINm5F胰岛细胞中诱导的线粒体功能障碍。

Oligomannuronate prevents mitochondrial dysfunction induced by IAPP in RINm5F islet cells by inhibition of JNK activation and cell apoptosis.

作者信息

Liu Xi, Li Qiong, Cheng Xiaolei, Liu Zhichun, Zhao Xiaoliang, Zhang Shuai, Yu Guangli, Zhao Xia, Hao Jiejie

机构信息

1Laboratory for Marine Drugs and Bioproducts, Qingdao National Laboratory for Marine Science and Technology, Qingdao, 266237 China.

2School of Medicine and Pharmacy, Ocean University of China, Qingdao, 266003 China.

出版信息

Chin Med. 2020 Mar 24;15:27. doi: 10.1186/s13020-020-00310-4. eCollection 2020.

DOI:10.1186/s13020-020-00310-4
PMID:32226477
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7092590/
Abstract

BACKGROUND

Oligomannuronates (OM) are natural products from alginate that is frequently used as food supplement. The aim of this study was to investigate the in vitro protective effects of OM on RINm5F cells against human Islet amyloid polypeptide (IAPP) induced mitochondrial dysfunction, as well as the underlying mechanisms.

METHODS

In the present study, we obtained several kinds of OM with different molecular masses, and then we used RINm5F cells as a model to elucidate the involvement of JNK signal pathway in hIAPP-induced mitochondrial dysfunction in pancreatic beta cells, and the protective effects of OM are associated with its ability to attenuate the mitochondrial dysfunction.

RESULTS

Our results demonstrated that human IAPP induced mitochondrial dysfunction, as evidence by loss of ΔΨm and ATP content, and decrease in oxygen consumption and complex activities, was accompanied by JNK activation, changes in the expressions of Bcl-2 and Bax proteins, release of cytochrome c (Cyto-c) and apoptosis inducing factor (AIF) from mitochondria into cytosol. Interestingly, the human IAPP induced damage in RINm5F cells were effectively restored by co-treatment of OM. Moreover, JNK activation was required for the OM mediated changes in RINm5F cells.

CONCLUSIONS

OM prevented mitochondrial dysfunction induced by human IAPP in RINm5F islet cells through JNK dependent signaling pathways.

摘要

背景

寡聚甘露糖醛酸（OM）是藻酸盐的天然产物，藻酸盐常被用作食品补充剂。本研究的目的是探讨OM对RINm5F细胞在抵抗人胰岛淀粉样多肽（IAPP）诱导的线粒体功能障碍方面的体外保护作用及其潜在机制。

方法

在本研究中，我们获得了几种不同分子量的OM，然后以RINm5F细胞为模型，阐明JNK信号通路在hIAPP诱导的胰腺β细胞线粒体功能障碍中的作用，以及OM的保护作用与其减轻线粒体功能障碍的能力有关。

结果

我们的结果表明，人IAPP诱导线粒体功能障碍，表现为线粒体膜电位（ΔΨm）丧失、ATP含量降低、氧消耗和复合物活性下降，同时伴有JNK激活、Bcl-2和Bax蛋白表达变化、细胞色素c（Cyto-c）和凋亡诱导因子（AIF）从线粒体释放到细胞质中。有趣的是，OM共同处理有效地恢复了人IAPP对RINm5F细胞的损伤。此外，JNK激活是OM介导RINm5F细胞变化所必需的。

结论

OM通过JNK依赖的信号通路预防人IAPP诱导的RINm5F胰岛细胞线粒体功能障碍。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d20c/7092590/ff89ec0c7206/13020_2020_310_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d20c/7092590/b3e340cff2e3/13020_2020_310_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d20c/7092590/a809ee74d599/13020_2020_310_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d20c/7092590/76315d01b286/13020_2020_310_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d20c/7092590/d66c0835c822/13020_2020_310_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d20c/7092590/f0b8d9e0f045/13020_2020_310_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d20c/7092590/ff89ec0c7206/13020_2020_310_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d20c/7092590/b3e340cff2e3/13020_2020_310_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d20c/7092590/a809ee74d599/13020_2020_310_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d20c/7092590/76315d01b286/13020_2020_310_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d20c/7092590/d66c0835c822/13020_2020_310_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d20c/7092590/f0b8d9e0f045/13020_2020_310_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d20c/7092590/ff89ec0c7206/13020_2020_310_Fig6_HTML.jpg

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