Paclobutrazol exposure induces apoptosis and impairs autophagy in hepatocytes via the AMPK/mTOR signaling pathway

被引:5
作者
Luo, Yun [1 ,2 ,3 ]
Lu, Shan [1 ,2 ,3 ]
Sun, Xiao [1 ,2 ,3 ]
Gao, Ye [1 ]
Sun, Guibo [1 ,2 ,3 ]
Yang, Meihua [1 ,2 ]
Sun, Xiaobo [1 ,2 ,3 ]
机构
[1] Peking Union Med Coll & Chinese Acad Med Sci, Inst Med Plant Dev, Beijing 100193, Peoples R China
[2] Minist Educ, Key Lab Bioact Subst & Resources Utilizat Chinese, Beijing, Peoples R China
[3] Beijing Key Lab Innovat Drug Discovery Tradit Chi, Beijing, Peoples R China
关键词
AKT; mTOR signaling pathway; apoptosis; autophagy; hepatocyte; paclobutrazol; ZEBRAFISH DANIO-RERIO; OPHIOPOGON-JAPONICUS; CELL-DEATH; ACTIVATION; TOXICITY;
D O I
10.1002/jbt.22874
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
Paclobutrazol (PBZ), one of the most widely used plant growth retardants in vegetables, fruits, and traditional Chinese medicine ingredients, exposes people to adverse events. In this study, HepaRG hepatocytes were cultured and exposed to PBZ (360 mu M) in vitro to determine its mechanism. Results showed that PBZ exposure inhibited cell viability in a time- and dose-dependent manner and increased the oxidative stress and apoptosis ratio in HepaRG cells. These data revealed that the adenosine monophosphate-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) has an important role in PBZ-induced cell apoptosis, which is mediated by impaired autophagy and blocked by the AMPK activator. In conclusion, PBZ exposure induces apoptosis and impairs autophagy in hepatocytes via the AMPK/mTOR signaling pathway.
引用
收藏
页数:9
相关论文
共 37 条
[1]   Ophiopogon japonicus-A phytochemical, ethnomedicinal and pharmacological review [J].
Chen, Min-Hui ;
Chen, Xiao-Jia ;
Wang, Mei ;
Lin, Li-Gen ;
Wang, Yi-Tao .
JOURNAL OF ETHNOPHARMACOLOGY, 2016, 181 :193-213
[2]  
Cyranoski D, 2018, NATURE, V561, P448, DOI 10.1038/d41586-018-06782-7
[3]   A Highly Selective Ratiometric Two-Photon Fluorescent Probe for Human Cytochrome P450 1A [J].
Dai, Zi-Ru ;
Ge, Guang-Bo ;
Feng, Lei ;
Ning, Jing ;
Hu, Liang-Hai ;
Jin, Qiang ;
Wang, Dan-Dan ;
Lv, Xia ;
Dou, Tong-Yi ;
Cui, Jing-Nan ;
Yang, Ling .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2015, 137 (45) :14488-14495
[4]   Developmental toxicity potential of paclobutrazol in the rat [J].
de Castro, VL ;
Goes, KP ;
Chiorato, SH .
INTERNATIONAL JOURNAL OF ENVIRONMENTAL HEALTH RESEARCH, 2004, 14 (05) :371-380
[5]  
De O.S.R., 2019, FOOD CHEM, V297, P24934
[6]   Oxidative stress and structure-activity relationship in the zebrafish (Danio rerio) under exposure to paclobutrazol [J].
Ding, Feng ;
Song, Wen H. ;
Guo, Jing ;
Gao, Min L. ;
Hu, Wei X. .
JOURNAL OF ENVIRONMENTAL SCIENCE AND HEALTH PART B-PESTICIDES FOOD CONTAMINANTS AND AGRICULTURAL WASTES, 2009, 44 (01) :44-50
[7]   A predictive data-driven framework for endocrine prioritization: a triazole fungicide case study [J].
Friedman, Katie Paul ;
Papineni, Sabitha ;
Marty, M. Sue ;
Yi, Kun Don ;
Goetz, Amber K. ;
Rasoulpour, Reza J. ;
Kwiatkowski, Pat ;
Wolf, Douglas C. ;
Blacker, Ann M. ;
Peffer, Richard C. .
CRITICAL REVIEWS IN TOXICOLOGY, 2016, 46 (09) :785-833
[8]   Programmed Cell Death in Animal Development and Disease [J].
Fuchs, Yaron ;
Steller, Hermann .
CELL, 2011, 147 (04) :742-758
[9]   The enantioselective effects and potential risks of paclobutrazol residue during cucumber pickling process [J].
Guo, Hao-Ming ;
Zhao, Yue ;
Yang, Mei-Nan Ou ;
Yang, Zhong-Hua ;
Li, Jian-Hong .
JOURNAL OF HAZARDOUS MATERIALS, 2020, 386
[10]   Watch What You (Self-) Eat: Autophagic Mechanisms that Modulate Metabolism [J].
Lahiri, Vikramjit ;
Hawkins, Wayne D. ;
Klionsky, Daniel J. .
CELL METABOLISM, 2019, 29 (04) :803-826