The molecular mechanism of the effect of benzo<italic>α</italic>pyrene on autophagy of molecular chaperones under simulated hypoxia

Fan Yang; Nan Lin; Sha-sha Zhang; Meng-di Zhang; Yu-xia HU; Tu-ya Bai; Xiao-li LÜ; Jun LI; Zhi-bin Xiao; Tuo-ya Ao-dun; Fu-hou Chang

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The molecular mechanism of the effect of benzoαpyrene on autophagy of molecular chaperones under simulated hypoxia

VernacularTitle:苯并芘在模拟缺氧环境下对分子伴侣自噬影响的分子机制
Author: Fan YANG ¹ ; Nan LIN ¹ ; Sha-sha ZHANG ¹ ; Meng-di ZHANG ^{1
,

2} ; Yu-xia HU ^{2
,

3} ; Tu-ya BAI ^{1
,

2} ; Xiao-li LÜ ^{1
,

2} ; Jun LI ^{2
,

3} ; Zhi-bin XIAO ^{1
,

2} ; Tuo-ya AO-DUN ⁴ ; Fu-hou CHANG ^{1
,

2
,

5}
Author Information

1. School of Pharmacy, Inner Mongolia Medical University, Hohhot 010110, China
2. Inner Mongolia New Drug Screening Engineering Research Center, Hohhot 010110, China
3. The Center for New Drug Safety Evaluation and Research, Inner Mongolia Medical University, Hohhot 010110, China
4. Affiliated Hospital of Inner Mongolia Medical University, Hohhot 010110, China
5. The Center for New Drug Safety Evaluation and Research, Inner Mongolia Medical University, Hohhot 010110, China
Publication Type:Research Article
Keywords: hypoxia; benzo[α]pyrene; chaperone-mediated autophagy; hypoxia inducible factor-1α; heat shock protein 90; DNA damage
From: Acta Pharmaceutica Sinica 2020;55(11):2665-2673
CountryChina
Language:Chinese
Abstract: In this study, the effect of benzo[α]pyrene (BaP) on chaperone-mediated autophagy (CMA) in a simulated hypoxia environment was observed and the relationship to heat shock protein 90 (HSP90) was clarified. With HSP90 inhibitor geldanamycin (GA) and HSP90α silenced, the mRNA and protein expression of hypoxia-inducible factor-1α (HIF-1α), HSP90, heat shock cognate protein 70 (HSC70), and lysosomal associated protein 2A (LAMP-2A) of A549 cells on hypoxic environment by BaP were tested. Alkaline comet experiment, immunofluorescence γ-H2AX focus experiment, quantitative real-time PCR (qPCR), and Western blot analyses were used to clarify the relationship between the DNA damage of different concentrations of BaP in A549 cells and the mRNA and protein expression of CMA-related factors. The results show that hypoxia can promote the expression of mRNA and protein of CMA-related factors in A549 cells. This study found that BaP has an inhibitory effect on CMA under the hypoxic environment. The inhibition or silencing of HSP90 will enhance the inhibitory effect of BaP on CMA. In a normoxic environment, BaP causes DNA damage and promotes CMA.