Silica dust exposure induces autophagy in alveolar macrophages through switching Beclin1 affinity from Bcl‐2 to PIK3C3

• DOI: 10.1002/tox.22910
• Publication Date: 2020-02-15T14:10:37Z
• Authors: Pan Yang; Ruirui Song; Ning Li; Kun Sun; Fan Shi; Heliang Liu; Fuhai Shen; Shoufang Jiang; Lin Zhang; Yulan Jin
• Keywords: Silicosis

Abstract Increased deposition of silica dust in pulmonary interstitial tissues leads to silicosis, which autophagy plays a defensive role dust‐associated stress response and cell death. Our previous studies revealed that exposure contributed macrophages vivo, while the specific regulatory mechanism is still unclear. This study aimed figure out as well pathogenesis experimental silicosis. We used 3‐methyladenine (3‐MA) ABT‐737 suppress expression phosphatidylinositol 3‐kinase catalytic subunit type 3 (PIK3C3) B leukemia/lymphoma 2 (Bcl‐2), two critical initiators autophagy, detected evaluated NR8383 cells with or without exposure. found increased elevated Beclin1 PIK3C3, but it reduced Bcl‐2. The relationship among Beclin1, Bcl‐2 were then investigated using immunoprecipitation analysis, we suppression PIK3C3 and/or 3‐MA could alter induced by cells, complexes Beclin1/PIK3C3 Beclin1/Bcl‐2 both downregulated, may be inhibition altered affinity lead silence signaling. These findings indicate induces via changing connectivity from PIK3C3.