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Silica dust exposure induces autophagy in alveolar macrophages through switching Beclin1 affinity from Bcl-2 to PIK3C3
- Source :
- Environmental toxicologyREFERENCES. 35(7)
- Publication Year :
- 2019
-
Abstract
- Increased deposition of silica dust in pulmonary interstitial tissues leads to silicosis, in which autophagy plays a defensive role in silica dust-associated stress response and cell death. Our previous studies revealed that silica dust exposure contributed to autophagy in pulmonary macrophages in vivo, while the specific regulatory mechanism is still unclear. This study aimed to figure out the regulatory mechanism as well as the role of autophagy in the pathogenesis of experimental silicosis. We used 3-methyladenine (3-MA) and ABT-737 to suppress the expression of phosphatidylinositol 3-kinase catalytic subunit type 3 (PIK3C3) and B cell leukemia/lymphoma 2 (Bcl-2), two critical initiators of autophagy, and detected and evaluated the autophagy in NR8383 cells with or without silica dust exposure. We found that exposure of silica dust increased autophagy in NR8383 cells and elevated the expression of Beclin1 and PIK3C3, but it reduced the expression of Bcl-2. The relationship among Beclin1, PIK3C3, and Bcl-2 were then investigated using immunoprecipitation analysis, and we found that suppression of PIK3C3 and/or Bcl-2 using 3-MA and/or ABT-737 could alter the autophagy induced by silica dust in NR8383 cells, and the complexes of Beclin1/PIK3C3 and Beclin1/Bcl-2 were both downregulated, which may be that inhibition of PIK3C3 and Bcl-2 altered the affinity of Beclin1 with PIK3C3 and Bcl-2 and lead to the silence of PIK3C3 signaling. These findings indicate that silica dust exposure induces autophagy via changing the connectivity of Beclin1 from Bcl-2 to PIK3C3.
- Subjects :
- Programmed cell death
Immunoprecipitation
Health, Toxicology and Mutagenesis
Silicosis
010501 environmental sciences
Management, Monitoring, Policy and Law
Toxicology
01 natural sciences
Piperazines
Cell Line
Pathogenesis
Nitrophenols
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
In vivo
Macrophages, Alveolar
medicine
Autophagy
Animals
Humans
Phosphatidylinositol
0105 earth and related environmental sciences
Air Pollutants
Sulfonamides
Chemistry
Biphenyl Compounds
Dust
General Medicine
medicine.disease
Silicon Dioxide
Class III Phosphatidylinositol 3-Kinases
Cell biology
Rats
Proto-Oncogene Proteins c-bcl-2
030220 oncology & carcinogenesis
B-cell leukemia
Beclin-1
Signal Transduction
Subjects
Details
- ISSN :
- 15227278
- Volume :
- 35
- Issue :
- 7
- Database :
- OpenAIRE
- Journal :
- Environmental toxicologyREFERENCES
- Accession number :
- edsair.doi.dedup.....cea84b6b4a586f9d5c21f2cdbb1d80da