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多糖通过恢复线粒体功能和调节 MAPK 和 AMPK/Akt/mTOR 信号通路预防棕榈酸诱导的肠上皮细胞凋亡和自噬。

Polysaccharides Prevent Palmitic Acid-Evoked Apoptosis and Autophagy in Intestinal Porcine Epithelial Cell Line via Restoration of Mitochondrial Function and Regulation of MAPK and AMPK/Akt/mTOR Signaling Pathway.

机构信息

Hunan Agricultural Product Processing Institute, Hunan Academy of Agricultural Sciences, Changsha 410125, China.

College of Veterinary Medicine, Hunan Agricultural University, Changsha 410128, China.

出版信息

Int J Mol Sci. 2019 Jan 23;20(3):478. doi: 10.3390/ijms20030478.

DOI:10.3390/ijms20030478
PMID:30678035
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6387170/
Abstract

polysaccharide (GLP) extracted from (Leyss. ex Fr.) Karst, a traditional Chinese medicine, is a biologically active substance reported to possess anti-oxidative, anti-apoptotic, and neurological protection. However, it is unknown whether GLP have any protective effect against high-fat constituents-induced epithelial cell injury. The aim of this study was to investigate the protection and molecular mechanism of GLP on injury induced by palmitic acid (PA) in the intestinal porcine epithelial cell line (IPEC-J2). First, we tested whether the treatment of GLP attenuate PA-induced IPEC-J2 cell death. GLP markedly blocked PA-caused cytotoxicity and apoptosis in IPEC-J2 cells. Moreover, GLP recovered the decreased mitochondrial function and inhibited activation of caspase-dependent apoptotic pathway. Interestingly, PA promoted cell apoptosis and autophagy through stimulation of phosphorylation of mitogen-activated protein kinases (MAPKs), AMP-activated protein kinase (AMPK), and inhibition of phosphorylation of Akt and mammalian target of rapamycin (mTOR), which was reversed by GLP. Taken together, this study revealed a protective effect of GLP against PA-evoked IPEC-J2 cell death through anti-apoptotic and anti-autophagic properties.

摘要

从（Leyss. ex Fr.）Karst 中提取的多糖（GLP）是一种具有生物活性的物质，据报道具有抗氧化、抗凋亡和神经保护作用。然而，目前尚不清楚 GLP 是否对高脂肪成分诱导的上皮细胞损伤有任何保护作用。本研究旨在探讨 GLP 对猪肠上皮细胞系（IPEC-J2）中棕榈酸（PA）诱导的损伤的保护作用及其分子机制。首先，我们检测了 GLP 是否能减轻 PA 诱导的 IPEC-J2 细胞死亡。GLP 显著抑制了 PA 引起的 IPEC-J2 细胞毒性和凋亡。此外，GLP 恢复了因 PA 引起的线粒体功能下降，并抑制了 caspase 依赖性凋亡途径的激活。有趣的是，PA 通过刺激丝裂原活化蛋白激酶（MAPKs）、AMP 激活蛋白激酶（AMPK）的磷酸化和抑制 Akt 和雷帕霉素靶蛋白（mTOR）的磷酸化来促进细胞凋亡和自噬，而 GLP 则逆转了这一过程。综上所述，本研究揭示了 GLP 通过抗凋亡和抗自噬特性对 PA 诱导的 IPEC-J2 细胞死亡的保护作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/547c/6387170/6d9869ef5ac1/ijms-20-00478-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/547c/6387170/a46a4268dcdd/ijms-20-00478-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/547c/6387170/77c78de67e4c/ijms-20-00478-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/547c/6387170/5cdaad06f213/ijms-20-00478-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/547c/6387170/8a8453f4e194/ijms-20-00478-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/547c/6387170/f7cba29a55a8/ijms-20-00478-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/547c/6387170/6d9869ef5ac1/ijms-20-00478-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/547c/6387170/a46a4268dcdd/ijms-20-00478-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/547c/6387170/77c78de67e4c/ijms-20-00478-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/547c/6387170/5cdaad06f213/ijms-20-00478-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/547c/6387170/8a8453f4e194/ijms-20-00478-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/547c/6387170/f7cba29a55a8/ijms-20-00478-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/547c/6387170/6d9869ef5ac1/ijms-20-00478-g006.jpg

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本文引用的文献

[1]
Hypolipidemic, Antioxidant, and Antiapoptotic Effects of Polysaccharides Extracted from Reishi Mushroom, Ganoderma lucidum (Leysser: Fr) Karst, in Mice Fed a High-Fat Diet.

J Med Food. 2018-12

[2]
Dietary Supplementation of Potato Peel Powders Prepared from Conventional and Organic Russet and Non-organic Gold and Red Potatoes Reduces Weight Gain in Mice on a High-Fat Diet.

J Agric Food Chem. 2018-6-7

[3]
Disruption of the beclin 1-BCL2 autophagy regulatory complex promotes longevity in mice.

Nature. 2018-5-30

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Cell. 2018-5-17

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High Levels of Avenanthramides in Oat-Based Diet Further Suppress High Fat Diet-Induced Atherosclerosis in Ldlr Mice.

J Agric Food Chem. 2018-1-17

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Neural Regen Res. 2017-6

[7]
Inhibition of Autophagy Promotes Salinomycin-Induced Apoptosis via Reactive Oxygen Species-Mediated PI3K/AKT/mTOR and ERK/p38 MAPK-Dependent Signaling in Human Prostate Cancer Cells.

Int J Mol Sci. 2017-5-18

[8]
Respiratory Muscle Training Improves Diaphragm Citrate Synthase Activity and Hemodynamic Function in Rats with Heart Failure.

Braz J Cardiovasc Surg. 2017

[9]
Reduced expression of citrate synthase leads to excessive superoxide formation and cell apoptosis.

Biochem Biophys Res Commun. 2017-4-1

[10]
Therapeutic properties in Tunisian hot springs: first evidence of phenolic compounds in the cyanobacterium Leptolyngbya sp. biomass, capsular polysaccharides and releasing polysaccharides.

BMC Complement Altern Med. 2016-12-13

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