Luteolin, a natural flavonoid, inhibits methylglyoxal induced apoptosis via the mTOR/4E-BP1 signaling pathway

被引:33
作者
Liu, Yi [1 ]
Huang, Jie [1 ]
Zheng, Xian [1 ]
Yang, Xia [1 ]
Ding, Yan [1 ]
Fang, Tongyong [1 ]
Zhang, Yuyun [1 ]
Wang, Shuaishuai [1 ]
Zhang, Xiaofei [1 ]
Luo, Xuan [1 ]
Guo, Anlei [1 ]
Newell, Kelly A. [3 ]
Yu, Yinghua [2 ,3 ]
Huang, Xu-Feng [2 ,3 ]
机构
[1] Xuzhou Med Univ, Jiangsu Key Lab New Drug Res & Clin Pharm, Xuzhou, Jiangsu, Peoples R China
[2] Xuzhou Med Univ, Dept Pathogen Biol & Immunol, Jiangsu Key Lab Immun & Metab, Xuzhou 221004, Peoples R China
[3] Univ Wollongong, Fac Sci Med & Hlth, Illawarra Hlth & Med Res Inst, Wollongong, NSW 2522, Australia
来源
SCIENTIFIC REPORTS | 2017年 / 7卷
基金
中国国家自然科学基金;
关键词
PC12 CELL APOPTOSIS; DIABETIC ENCEPHALOPATHY; OXIDATIVE STRESS; KAPPA-B; MTOR; HIPPOCAMPUS; DYSFUNCTION; PROTECTS; DEFICITS; BRAIN;
D O I
10.1038/s41598-017-08204-6
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Methylglyoxal (MG) accumulation has been observed in human cerebrospinal fluid and body tissues under hyperglycaemic conditions. Recent research has demonstrated that MG-induces neuronal cell apoptosis, which promotes the development of diabetic encephalopathy. Our previous animal study has shown that luteolin, a natural flavonoid, attenuates diabetes-associated cognitive dysfunction. To further explore the neuroprotective properties of luteolin, we investigated the inhibitive effect of luteolin on MG-induced apoptosis in PC12 neuronal cells. We found that MG inhibited cell viability in a dose-dependent manner and induced apoptosis in PC12 cells. Pretreatment with Luteolin significantly elevated cell viability, reduced MG-induced apoptosis, inhibited the activation of the mTOR/4E-BP1 signaling pathway, and decreased pro-apoptotic proteins, Bax, Cytochrome C as well as caspase-3. Furthermore, we found that pretreatment with the mTOR inhibitor, rapamycin, significantly reduced the expression of the pro-apoptotic protein Bax. Therefore, these observations unambiguously suggest that the inhibitive effect of Luteolin against MG-induced apoptosis in PC12 cells is associated with inhibition of the mTOR/4E-BP1 signaling pathway.
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页数:11
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