Swainsonine induces autophagy via PI3K/AKT/mTOR signaling pathway to injure the renal tubular epithelial cells

被引：17

作者：

Wang, Shuai ^{[1
]}

Wang, Jinglong ^{[2
]}

Yang, Lin ^{[1
]}

Guo, Rong ^{[1
]}

Huang, Enxia ^{[1
]}

Yang, Hanqi ^{[1
]}

Zhang, Yajing ^{[1
]}

Sun, Lu ^{[1
]}

Song, Runjie ^{[1
]}

Chen, Jingshu ^{[3
]}

Tian, Yanan ^{[3
]}

Zhao, Baoyu ^{[1
]}

Guo, Qingyun ^{[4
]}

Lu, Hao ^{[1
]}

机构：

[1] Northwest A&F Univ, Coll Vet Med, Yangling 712100, Shaanxi, Peoples R China

[2] State Key Lab Barley & Yak Germplasm Resources &, Lhasa 850002, Tibet, Peoples R China

[3] Texas A&M Univ, Coll Vet Med, Dept Vet Physiol & Pharmacol, College Stn, TX 77843 USA

[4] Key Lab Agr Integrated Pest Management, Xining 810016, Qinghai, Peoples R China

来源：

BIOCHIMIE | 2019年 / 165卷

基金：

中国国家自然科学基金;

关键词：

Locoweed; Swainsonine; Vacuolar degeneration; Autophagy; PI3K/Akt/mTOR pathway; ALPHA-MANNOSIDASE; APOPTOSIS; LOCOWEED; CASTANOSPERMINE; INHIBITION; DEFICIENCY; INSIGHTS; LESIONS; ATG5;

D O I：

10.1016/j.biochi.2019.07.018

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Swainsonine is a major toxic ingredients of locoweed plants, ingestion of these plants may cause locoism in livestock characterized by extensive cellular vacuolar degeneration of multiple tissues. However, so far, the mechanisms responsible for vacuolar degeneration induced by SW are not known. In this study, we investigated the role of autophagy in SW-induced TCMK-1 cells using Western blotting, transmission electron microscopy, immunofluorescent microscopy and qRT-PCR. The results showed that SW treatment increased the levels of LC3-II. The co-localization of LC3-II and lysosomal protein LAMP-2 results suggested that SW treatment does not interfere with fusion between autophagosome and lysosome. TEM results indicated that SW induced aggregation of the lysosome around the autophagosome. In addition, SW treatment suppressed p-PI3K, p-Akt, p-mTOR, p-p70S6K and p-4EBP1 level. In conclusion, SW induced autophagy via pI3K/AKT/mTOR signaling pathway and revealed the role of autophagy in causing the SW toxicity characterized by the vacuolar degeneration. (C) 2019 Elsevier B.V. and Societe Francaise de Biochimie et Biologie Moleculaire (SFBBM). All rights reserved.

引用

页码：131 / 140

页数：10

共 47 条

[1] p62/SQSTM1 forms protein aggregates degraded by autophagy and has a protective effect on huntingtin-induced cell death [J].

Bjorkoy, G ;

Lamark, T ;

Brech, A ;

Outzen, H ;

Perander, M ;

Overvatn, A ;

Stenmark, H ;

Johansen, T .

JOURNAL OF CELL BIOLOGY, 2005, 171 (04) :603-614

[2]

COOK D., 2009, RANGELANDS, V31, P16, DOI DOI 10.2111/1551-501X-31.1.16

[3] TORC-Specific Phosphorylation of Mammalian Target of Rapamycin (mTOR): Phospho-Ser2481 Is a Marker for Intact mTOR Signaling Complex 2 [J].

Copp, Jeremy ;

Manning, Gerard ;

Hunter, Tony .

CANCER RESEARCH, 2009, 69 (05) :1821-1827

[4]

Creamer R., 2013, FUNGAL ENDOPHYTES LO

[5] INHIBITION OF LYSOSOMAL ALPHA-MANNOSIDASE BY SWAINSONINE, AN INDOLIZIDINE ALKALOID ISOLATED FROM SWAINSONA-CANESCENS [J].

DORLING, PR ;

HUXTABLE, CR ;

COLEGATE, SM .

BIOCHEMICAL JOURNAL, 1980, 191 (02) :649-651

[6] Endoplasmic reticulum stress induces autophagy and apoptosis while inhibiting proliferation and drug resistance in multiple myeloma through the PI3K/Akt/mTOR signaling pathway [J].

Fu, Yun-Feng ;

Liu, Xiao ;

Gao, Meng ;

Zhang, Ya-Nan ;

Liu, Jing .

ONCOTARGET, 2017, 8 (37) :61093-61106

[7]

Furlan S., 2011, International Journal of Poisonous Plant Research, V1, P35

[8] Autophagy and cell death [J].

Gozuacik, Devrim ;

Kimchi, Adi .

CURRENT TOPICS IN DEVELOPMENTAL BIOLOGY, VOL 78, 2007, 78 :217-245

[9] Analysis of a New Family of Widely Distributed Metal-independent α-Mannosidases Provides Unique Insight into the Processing of N-Linked Glycans [J].

Gregg, Katie J. ;

Zandberg, Wesley F. ;

Hehemann, Jan-Hendrik ;

Whitworth, Garrett E. ;

Deng, Lehua ;

Vocadlo, David J. ;

Boraston, Alisdair B. .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2011, 286 (17) :15586-15596

[10] Induction of apoptosis and autophagy via mitochondria- and PI3K/Akt/mTOR-mediated pathways by E. adenophorum in hepatocytes of saanen goat [J].

He, Yajun ;

Mo, Quan ;

Luo, Biao ;

Qiao, Yan ;

Xu, Ruiguang ;

Zuo, Zhicai ;

Deng, Junliang ;

Nong, Xiang ;

Peng, Guangneng ;

He, Wei ;

Wei, Yahui ;

Hu, Yanchun .

ONCOTARGET, 2016, 7 (34) :54537-54548

← 1 2 3 4 5 →