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4-苯丁酸通过调节线粒体相关内质网膜和 NLRP-3 减轻大豆球蛋白/β-伴大豆球蛋白诱导的 IPEC-J2 细胞凋亡。

4-Phenylbutyric Acid Attenuates Soybean Glycinin/β-Conglycinin-Induced IPEC-J2 Cells Apoptosis by Regulating the Mitochondria-Associated Endoplasmic Reticulum Membrane and NLRP-3.

机构信息

College of Animal Science and Technology, Anhui Agricultural University, Hefei 230061, China.

Anhui Province Key Laboratory of Livestock and Poultry Product Safety Engineering, Institute of Animal Science and Veterinary Medicine, Anhui Academy of Agricultural Sciences, Hefei 230031, China.

出版信息

J Agric Food Chem. 2024 Mar 20;72(11):5926-5934. doi: 10.1021/acs.jafc.3c09630. Epub 2024 Mar 8.

DOI:10.1021/acs.jafc.3c09630
PMID:38457471
Abstract

Glycinin (11S) and β-conglycinin (7S) from soybean (glycine max) cause diarrhea and intestinal barrier damage in young animals. Understanding the mechanisms underlying the damage caused by 7S and 11S, it is vital to develop strategies to eliminate allergenicity. Consequently, we investigated 7S/11S-mediated apoptosis in porcine intestinal epithelial (IPEC-J2) cells. IPEC-J2 cells suffered endoplasmic reticulum stress (ERS) in response to 7S and 11S, activating protein kinase RNA-like ER kinase, activating transcription factor 6, C/EBP homologous protein, and inositol-requiring enzyme 1 alpha. 4-Phenylbutyric acid (4-PBA) treatment alleviated ERS; reduced the NLR family pyrin domain containing 3, interleukin-1β, and interleukin-18 levels; inhibited apoptosis; increased mitofusin 2 expression; and mitigated Ca overload and mitochondria-associated ER membrane (MAM) dysfunction, thereby ameliorating IPEC-J2 injury. We demonstrated the pivotal role of ERS in MAM dysfunction and 7S- and 11S-mediated apoptosis, providing insights into 7S- and 11S-mediated intestinal barrier injury prevention and treatment.

摘要

大豆中的 Glycinin(11S)和β-conglycinin(7S)可引起幼小动物腹泻和肠道屏障损伤。了解 7S 和 11S 引起损伤的机制对于消除其致敏性至关重要。因此,我们研究了 7S/11S 介导的猪肠上皮(IPEC-J2)细胞凋亡。7S 和 11S 可诱导 IPEC-J2 细胞发生内质网应激(ERS),激活蛋白激酶 RNA 样内质网激酶、激活转录因子 6、C/EBP 同源蛋白和肌醇需求酶 1α。4-苯丁酸(4-PBA)处理可减轻 ERS;降低 NLR 家族富含吡啶结构域蛋白 3、白细胞介素-1β和白细胞介素-18 水平;抑制细胞凋亡;增加线粒体融合蛋白 2 表达;减轻钙超载和线粒体相关内质网膜(MAM)功能障碍,从而改善 IPEC-J2 损伤。我们证明了 ERS 在 MAM 功能障碍和 7S 和 11S 介导的细胞凋亡中的关键作用,为预防和治疗 7S 和 11S 介导的肠道屏障损伤提供了新的思路。

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