Laboratory of Clinical Pharmaceutics, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu 501-1196, Japan.
J Clin Biochem Nutr. 2013 Mar;52(2):101-5. doi: 10.3164/jcbn.12-46. Epub 2013 Feb 1.
Endoplasmic reticulum stress is related to metabolic disorders, including atherosclerosis and type 2 diabetes. It is known that inflammatory adipocytokines and oxidative stress are increased, while anti-inflammatory adipocytokines such as adiponectin are decreased in adipocytes during above conditions. Extracellular-superoxide dismutase is an anti-inflammatory enzyme that protects cells from oxidative stress. Because plasma extracellular-superoxide dismutase levels in type 2 diabetes patients were inversely related to the body mass index and homeostasis model assessment-insulin resistance index, it is speculated that the regulation of extracellular-superoxide dismutase might lead to the suppression of metabolic disorders. Here, we observed the reduction of extracellular-superoxide dismutase and adiponectin in 3T3-L1 adipocytes treated with thapsigargin, an endoplasmic reticulum stress inducer. Interestingly, tunicamycin, another endoplasmic reticulum stress inducer, did not decrease the expression of extracellular-superoxide dismutase in spite of the induction of glucose regulated protein kinase 78 kDa, an endoplasmic reticulum stress marker. Moreover, eukaryotic translation initiation factor 2α signaling cascade plays a pivotal role in the reduction of extracellular-superoxide dismutase in 3T3-L1 adipocytes during endoplasmic reticulum stress conditions.
内质网应激与代谢紊乱有关，包括动脉粥样硬化和 2 型糖尿病。已知在上述情况下，脂肪细胞中炎症性脂肪细胞因子增加，而抗炎性脂肪细胞因子如脂联素减少。细胞外超氧化物歧化酶是一种抗炎酶，可保护细胞免受氧化应激。由于 2 型糖尿病患者的血浆细胞外超氧化物歧化酶水平与体重指数和稳态模型评估-胰岛素抵抗指数呈负相关，因此推测细胞外超氧化物歧化酶的调节可能导致代谢紊乱的抑制。在这里，我们观察到内质网应激诱导剂他普西龙处理的 3T3-L1 脂肪细胞中外泌型超氧化物歧化酶和脂联素的减少。有趣的是，尽管诱导了内质网应激标志物葡萄糖调节蛋白 78 kDa，但另一种内质网应激诱导剂衣霉素并没有降低细胞外超氧化物歧化酶的表达。此外，真核翻译起始因子 2α信号级联在 3T3-L1 脂肪细胞内质网应激条件下细胞外超氧化物歧化酶的减少中起着关键作用。
