异硫氰酸烯丙酯对分泌胰岛素的 INS-1E 细胞的细胞毒性。

IF 2 4区 医学 Q3 PHYSIOLOGY Journal of Physiology and Pharmacology Pub Date : 2024-06-01 Epub Date: 2024-07-18 DOI:10.26402/jpp.2024.3.04
M Okulicz, M Billert, T Wojciechowicz, M Skrzypski
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引用次数: 0

摘要

异硫氰酸烯丙酯(AITC)是黄铜类植物的辛辣成分,可用作食品添加剂和调味剂,包括芥末、辣根和芥末等调味品。目前,许多证据表明 AITC 可调节葡萄糖和脂质代谢。有趣的是,AITC 已被证明能改善 T2DM 大鼠的血糖和胰岛素作用,并能诱导血胰岛素水平进一步下降。因此,在本研究中,我们研究了 AITC 在较宽浓度范围(5、10、25、50、100 μM)内对 INS-1E 细胞的活力、增殖、凋亡、线粒体状态、编码胰腺和十二指肠同工酶 1(Pdx1)和 Ins1、Ins2 基因的 mRNA 表达以及胰岛素含量的控制作用。INS-1E细胞系是研究β细胞功能的一个合适且特性良好的模型。我们发现,AITC 会降低 INS-1E 细胞的存活率(p≤0.001)(在瞬时受体电位阳离子亚家族 A 成员 1(TRPA1)选择性拮抗剂 HC-030031 的作用下也是如此;p≤0.05)和增殖率(p≤0.001)。AITC 能显著降低线粒体膜电位(p≤0.01),降低细胞内三磷酸腺苷(ATP)水平(p≤0.001),但不影响活性氧(ROS)水平。此外,AITC 还抑制 INS-1E 细胞中胰岛素 mRNA 的表达(p≤0.001)和胰岛素含量(p≤0.05)。线粒体功能障碍被认为是 AITC 对 INS-1E 细胞的一个重要破坏机制,它与 ROS 和外部钙离子的流入无关。
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Cytotoxicity of allyl isothiocyanate on insulin-producing INS-1E cells.

Allyl isothiocyanate (AITC) is the pungent ingredient of brassica species, used as a food additive and flavoring agent, including condiments such as wasabi, horseradish, and mustard. Currently, there is much evidence that AITC modulates glucose and lipids metabolism. Interestingly, AITC has been shown to improve glycaemia, and insulin action along with the induction of a deepened decline in blood insulin levels in T2DM rats. Therefore, in the present study, we characterized the role of AITC at a wide concentration range (5, 10, 25, 50, 100 μM) in controlling viability, proliferation, apoptosis, mitochondrial condition, mRNA expression of encoding pancreatic and duodenal homeobox 1 (Pdx1), and Ins1, Ins2 genes, and insulin content in INS-1E cells. The INS-1E cell line is a suitable, and well-characterized model to study beta cell functions. We demonstrate that AITC reduced the viability (p≤0.001) (also in the presence of transient receptor potential cation subfamily A member 1 (TRPA1) selective antagonist; HC-030031; p≤0.05), and proliferation of INS-1E cells (p≤0.001). AITC evoked a significant reduction of mitochondrial membrane potential (p≤0.01) and decreased the intracellular level of adenosine triphosphate (ATP) (p≤0.001) without influence on reactive oxygen species (ROS) level. Additionally, AITC inhibited the insulin mRNA expression (p≤0.001) in INS-1E cells along with insulin content (p≤0.05). Mitochondrial dysfunction is proposed to be a significant disruption mechanism of AITC in INS-1E cells, and it was independent of ROS, and the influx of external calcium.

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CiteScore
4.00
自引率
22.70%
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6-12 weeks
期刊介绍: Journal of Physiology and Pharmacology publishes papers which fall within the range of basic and applied physiology, pathophysiology and pharmacology. The papers should illustrate new physiological or pharmacological mechanisms at the level of the cell membrane, single cells, tissues or organs. Clinical studies, that are of fundamental importance and have a direct bearing on the pathophysiology will also be considered. Letters related to articles published in The Journal with topics of general professional interest are welcome.
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