Germacrone protects against oxygen-glucose deprivation/reperfusion injury by inhibiting autophagy processes in PC12 cells

被引：14

作者：

Zhang, Jianxing ^{[1
]}

Yuan, Li ^{[1
]}

Wang, Sujie ^{[1
]}

Liu, Jiang ^{[2
]}

Bi, Huiqin ^{[1
]}

Chen, Guojuan ^{[1
]}

Li, Jingjing ^{[1
]}

Chen, Lili ^{[1
]}

机构：

[1] Tangshan Gongren Hosp, Dept Neurol 2, 27 Wenhua Rd, Tangshan City 063000, Hebei, Peoples R China

[2] Tangshan Gongren Hosp, Dept Anesthesiol 1, Tangshan City 063000, Hebei, Peoples R China

来源：

BMC COMPLEMENTARY MEDICINE AND THERAPIES | 2020年 / 20卷 / 01期

关键词：

PC12; cells; Oxygen-glucose deprivation/reperfusion; Germacrone; Autophagy; PI3K III/Beclin-1/Bcl-2; PI3K I/Akt/mTOR; STEM-CELLS; APOPTOSIS; ACTIVATION; PATHWAY; STRESS; DEATH; OGD/R; LINES; LC3;

D O I：

10.1186/s12906-020-2865-1

中图分类号：

R [医药、卫生];

学科分类号：

10 ;

摘要：

Background: Germacrone is an anti-inflammatory ingredient in the Chinese medicine zedoary turmeric. The purpose of this study was to explore the protective mechanism of germacrone against PC12 cells injury caused by oxygen-glucose deprivation/reperfusion (OGD/R). Methods: OGD/R injury model of PC12 cells was established by using OGD/R (2 h/24 h). The cell viability was assessed by MTT assay and LDH release. The ultrastructure of cells was observed by transmission electron microscopy (TEM). The expression of autophagy related proteins in cells was determined by Western Blot. Results: The results of ultrastructural observation showed that PC12 cells damaged by OGD/R showed typical autophagy characteristics. In addition, OGD/R observably up-regulated the expression of autophagy related proteins: the class III type phosphoinositide 3-kinase (PI3K III), light chain 3(LC3), and Beclin-1 in PC12 cells, and inhibited the expression of the class I type phosphoinositide 3-kinase (PI3K I), Protein kinase B (Akt), the mammalian target of rapamycin (mTOR), and B-cell lymphoma 2(Bcl-2) proteins. Furthermore, germacrone increased the cell viability of OGD/R-damaged PC12 cells by down-regulating the expression of LC3 protein in cells in a concentration-dependent manner. More importantly, germacrone significantly inhibited the expression of PI3K III, LC3, and Beclin-1 in OGD/R-injured PC12 cells, and up-regulated the expressionof PI3K I, Akt, mTOR, and Bcl-2 proteins in cells, and this inhibited or up-regulated effect was reversed by PI3K I inhibitor (ZSTK474). Conclusion: The above results indicated that germacrone could inhibit the autophagy effect in OGD/R injury model of PC12 cells, the mechanism of inhibition was regulated by PI3K III/Beclin-1/Bcl-2 and PI3K I/Akt/mTOR pathways, thereby improving the cell viability of PC12 cells and playing a neuroprotective role, which provided a new drug for the treatment of OGD/R.

引用

页数：10

共 45 条

[1] RETRACTED: Ganoderic acid A alleviates hypoxia-induced apoptosis, autophagy, and inflammation in rat neural stem cells through the PI3K/AKT/mTOR pathways (Retracted Article) [J].

Chang, Yanhua ;

Kong, Ruifang .

PHYTOTHERAPY RESEARCH, 2019, 33 (05) :1448-1456

[2]

Chen Qiong-Fang, 2017, Zhongguo Zhong Yao Za Zhi, V42, P3564, DOI 10.19540/j.cnki.cjcmm.20170731.006

[3] Halilectin-3, a Lectin from the Marine Sponge Haliclona caerulea, Induces Apoptosis and Autophagy in Human Breast Cancer MCF7 Cells Through Caspase-9 Pathway and LC3-II Protein Expression [J].

do Nascimento-Neto, Luiz G. ;

Cabral, Maria G. ;

Carneiro, Romulo F. ;

Silva, Zelia ;

Arruda, Francisco V. S. ;

Nagano, Celso S. ;

Fernandes, Alexandra R. ;

Sampaio, Alexandre H. ;

Teixeira, Edson H. ;

Videira, Paula A. .

ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY, 2018, 18 (04) :521-528

[4] In Vitro Antiviral Activity of Germacrone Against Porcine Reproductive and Respiratory Syndrome Virus [J].

Feng, Jiaping ;

Bai, Xiaolei ;

Cui, Tiantian ;

Zhou, Han ;

Chen, Yao ;

Xie, Jiexiong ;

Shi, Qingwei ;

Wang, Heng ;

Zhang, Guihong .

CURRENT MICROBIOLOGY, 2016, 73 (03) :317-323

[5] The Contribution of Melanoregulin to Microtubule-Associated Protein 1 Light Chain 3 (LC3) Associated Phagocytosis in Retinal Pigment Epithelium [J].

Frost, Laura S. ;

Lopes, Vanda S. ;

Bragin, Alvina ;

Reyes-Reveles, Juan ;

Brancato, Jennifer ;

Cohen, Art ;

Mitchell, Claire H. ;

Williams, David S. ;

Boesze-Battaglia, Kathleen .

MOLECULAR NEUROBIOLOGY, 2015, 52 (03) :1135-1151

[6] Cargo recognition and degradation by selective autophagy [J].

Gatica, Damian ;

Lahiri, Vikramjit ;

Klionsky, Daniel J. .

NATURE CELL BIOLOGY, 2018, 20 (03) :233-242

[7] Technical note: comparison of the PrestoBlue and LDH release assays with the MTT assay for skin viability assessment [J].

Gaucher, Sonia ;

Jarraya, Mohamed .

CELL AND TISSUE BANKING, 2015, 16 (03) :325-329

[8]

Gong Q-H, 2016, EVID-BASED COMPL ALT

[9]

Greene LA, 1978, CHEMOTHERAPY, V10

[10] Cocaine-mediated microglial activation involves the ER stress-autophagy axis [J].

Guo, Ming-Lei ;

Liao, Ke ;

Periyasamy, Palsamy ;

Yang, Lu ;

Cai, Yu ;

Callen, Shannon E. ;

Buch, Shilpa .

AUTOPHAGY, 2015, 11 (07) :995-1009

← 1 2 3 4 5 →