Hyperglycemia Induces Generation of Reactive Oxygen Species and Accelerates Apoptotic Cell Death in Salivary Gland Cells
Hyperglycemia Induces Generation of Reactive Oxygen Species and Accelerates Apoptotic Cell Death in Salivary Gland Cells
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DOI：
10.1159/000512639
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发表时间：
2021-02-08
期刊：
影响因子：
5
通讯作者：
Saito, Ichiro
中科院分区：
文献类型：
--
作者：
Matsumoto, Naoyuki;Omagari, Daisuke;Saito, Ichiro
简介：2 型糖尿病 (T2DM) 与多种全身血管症状和口干症相关。人们认为，高血糖引起的多尿和脱水会导致体内水量减少，导致唾液分泌减少，最终导致口干症。在 T2DM 中，活性氧 (ROS) 产生的增加会导致血管内皮细胞以及上皮组织（包括胰腺和角膜）的组织损伤。因此，在高血糖环境中的其他组织和腺体中也可能发生类似的现象。方法：使用T2DM模型小鼠（db/db）检查唾液腺组织损伤。进行转移酶介导的 dUTP 缺口末端标记 (TUNEL) 来评估组织损伤。测量丙二醛（MDA）和8-羟基-2'-脱氧鸟苷的水平、Bax/Bcl-2比值作为氧化应激的指标。此外，在高糖条件下培养小鼠唾液腺来源的正常细胞，评估体外ROS产生和细胞损伤。结果：体内外分析显示db/db小鼠唾液腺组织中TUNEL阳性细胞比例较高，MDA和8-羟基-2'-脱氧鸟苷水平较高。这表明高血糖诱导的氧化应激对唾液分泌相关的脂质和 DNA 造成了损害。为了分析高血糖促进 ROS 产生的机制，分离了小鼠唾液腺来源的细胞。高葡萄糖培养基的细胞培养增强了ROS的产生并促进了细胞凋亡和坏死。结论：这些发现提出了一种新机制，即高血糖诱导的 ROS 产生促进唾液腺损伤，导致唾液分泌不足。
Introduction: Type-2 diabetes mellitus (T2DM) is associated with several systemic vascular symptoms and xerostomia. It is considered that hyperglycemia-induced polyuria and dehydration cause decreased body-water volume, leading to decreased saliva secretion and, ultimately, xerostomia. In T2DM, increased production of reactive oxygen species (ROS) causes tissue damage to vascular endothelial cells as well as epithelial tissue, including pancreas and cornea. Hence, a similar phenomenon may occur in other tissues and glands in a hyperglycemic environment. Methods: Salivary gland tissue injury was examined, using T2DM model mouse (db/db). Transferase-mediated dUTP nick-end labeling (TUNEL) was conducted to evaluate tissue injury. The levels of malondialdehyde (MDA) and 8-hydroxy-2 '-deoxyguanosine, Bax/Bcl-2 ratio were measured as indicator of oxidative stress. Moreover, in vitro ROS production and cell injury was evaluated by mouse salivary gland-derived normal cells under high-glucose condition culture. Results: In vivo and in vitro analysis showed a higher percentage of TUNEL-positive cells and higher levels of MDA and 8-hydroxy-2 '-deoxyguanosine in salivary gland tissue of db/db mice. This suggests damage of saliva secretion-associated lipids and DNA by hyperglycemic-induced oxidative stress. To analyze the mechanism by which hyperglycemia promotes ROS production, mouse salivary gland-derived cells were isolated. The cell culture with high-glucose medium enhanced ROS production and promotes apoptotic and necrotic cell death. Conclusion: These findings suggest a novel mechanism whereby hyperglycemic-induced ROS production promotes salivary gland injury, resulting in hyposalivation.