Instituto de Investigación en Enfermedades Crónico-Degenerativas, Instituto Transdisciplinar de Investigación e Innovación en Salud, Departamento de Biología Molecular y Genómica, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, 44340 Guadalajara, Jalisco, México; Department of Pharmaceutical and Medicinal Chemistry, University of Münster, Corrensstraße 48, 48149 Münster, Germany.
Department of Pharmaceutical and Medicinal Chemistry, University of Münster, Corrensstraße 48, 48149 Münster, Germany.
Int J Biol Macromol. 2021 Sep 30;187:76-90. doi: 10.1016/j.ijbiomac.2021.07.088. Epub 2021 Jul 17.
Lupin γ-conglutin beneficially modulates glycemia, but whether it protects against oxidative and lipotoxic damage remains unknown. Here, we studied the effects of γ-conglutin on cell death provoked by hydrogen peroxide and palmitate in HepG2 hepatocytes and insulin-producing MIN6 cells, and if a modulation of mitochondrial potential and reactive oxygen species (ROS) levels was involved. We also investigated how γ-conglutin influences insulin secretion and electrical activity of β-cells. The increased apoptosis of HepG2 cells exposed to hydrogen peroxide was prevented by γ-conglutin, and the viability and ROS content in γ-conglutin-treated cells was similar to that of non-exposed cells. Additionally, γ-conglutin partially protected MIN6 cells against hydrogen peroxide-induced death. This was associated with a marked reduction in ROS. No significant changes were found in the mitochondrial potential of γ-conglutin-treated cells. Besides, we observed a partial protection against lipotoxicity only in hepatocytes. Unexpectedly, we found a transient inhibition of insulin secretion, plasma membrane hyperpolarization, and higher K channel currents in β-cells treated with γ-conglutin. Our data show that γ-conglutin protects against cell death induced by oxidative stress or lipotoxicity by decreasing ROS and might also indicate that γ-conglutin promotes a β-cell rest, which could be useful for preventing β-cell exhaustion in chronic hyperglycemia.
羽扇豆γ-伴大豆球蛋白有益地调节血糖，但它是否能防止氧化和脂毒性损伤仍不清楚。在这里，我们研究了γ-伴大豆球蛋白对 HepG2 肝细胞和胰岛素分泌 MIN6 细胞中过氧化氢和棕榈酸引起的细胞死亡的影响，以及线粒体电位和活性氧 (ROS) 水平的调节是否参与其中。我们还研究了 γ-伴大豆球蛋白如何影响β细胞的胰岛素分泌和电活动。过氧化氢暴露的 HepG2 细胞凋亡增加被 γ-伴大豆球蛋白所阻止，γ-伴大豆球蛋白处理的细胞的活力和 ROS 含量与未暴露细胞相似。此外，γ-伴大豆球蛋白部分保护 MIN6 细胞免受过氧化氢诱导的死亡。这与 ROS 的显著减少有关。γ-伴大豆球蛋白处理的细胞中线粒体电位没有明显变化。此外，我们仅在肝细胞中观察到对脂毒性的部分保护。出乎意料的是，我们发现用 γ-伴大豆球蛋白处理的β细胞中出现胰岛素分泌短暂抑制、质膜超极化和更高的 K 通道电流。我们的数据表明，γ-伴大豆球蛋白通过降低 ROS 来保护细胞免受氧化应激或脂毒性诱导的死亡，并且还可能表明 γ-伴大豆球蛋白促进β细胞静止，这对于预防慢性高血糖中的β细胞衰竭可能是有用的。
