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

Yang, Pan Chyr; Song, Ruirui; Li, Ning; Sun, Kun; Shi, Fan; Liu, Heliang; Shen, Fuhai; Jiang, Shiang‐Huei; Lin, Zhongqin; Jin, Yulan

doi:10.1002/tox.22910

Cited by 14 publications

(8 citation statements)

References 44 publications

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“…p53, as a tumor suppressor, activates autophagy, whereas the activated autophagy in turn suppresses p53 [114]. As mostly reported, the induced autophagy is accompanied by the disruption of the Beclin1/Bcl-2 complex, and then Bcl-2 is released from the complex to enhance cell survival [126]. In this regard, the three types of molecular changes may also involve in autophagy promoting drug resistance: inactivation of proapoptotic factors, activation of antiapoptotic effectors and enhancement of survival signals.…”

Section: Autophagy As a Guardian In Tumor Drug Resistancementioning

confidence: 78%

Targeting autophagy to overcome drug resistance: further developments

2020

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Inhibiting cell survival and inducing cell death are the main approaches of tumor therapy. Autophagy plays an important role on intracellular metabolic homeostasis by eliminating dysfunctional or unnecessary proteins and damaged or aged cellular organelles to recycle their constituent metabolites that enable the maintenance of cell survival and genetic stability and even promotes the drug resistance, which severely limits the efficacy of chemotherapeutic drugs. Currently, targeting autophagy has a seemingly contradictory effect to suppress and promote tumor survival, which makes the effect of targeting autophagy on drug resistance more confusing and fuzzier. In the review, we summarize the regulation of autophagy by emerging ways, the action of targeting autophagy on drug resistance and some of the new therapeutic approaches to treat tumor drug resistance by interfering with autophagy-related pathways. The full-scale understanding of the tumor-associated signaling pathways and physiological functions of autophagy will hopefully open new possibilities for the treatment of tumor drug resistance and the improvement in clinical outcomes.

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Section: Autophagy As a Guardian In Tumor Drug Resistancementioning

confidence: 78%

Targeting autophagy to overcome drug resistance: further developments

2020

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“…The control group cultured with normal culture medium, the DMSO group was treated with 0.1% DMSO and the AS-IV group was treated with AS-IV (50 µM). AS-IV 10+PM2.5 group and AS-IV 50+PM2.5 group were pre-treated with AS-IV (10 and 50 µM) for 12 h, then the cells were exposure to PM2.5 (50 ug/mL) for 24 h. In the last two groups, cells were pretreated with 3-MA (5mM) for 12 h followed by treatment with PM2.5 (50 ug/mL), 23 , 36 and treated with different drugs with or without AS-IV (50 µM) for 12 h.…”

Section: Methodsmentioning

confidence: 99%

Astragaloside IV Protects from PM2.5-Induced Lung Injury by Regulating Autophagy via Inhibition of PI3K/Akt/mTOR Signaling in vivo and in vitro

Pei¹,

Wang²,

Huang³

et al. 2021

JIR

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Introduction Prolonged exposure to air polluted with airborne fine particulate matter (PM2.5) can increase respiratory disease risk. Astragaloside IV (AS-IV) is one of the main bioactive substances in the traditional Chinese medicinal herb, Astragalus membranaceus Bunge. AS-IV has numerous pharmacological properties; whereas there are few reports on the prevention of PM2.5-induced lung injury by AS-IV through modulation of the autophagic pathway. This study aimed to investigate the protective effects and the underlying mechanisms of AS-IV in PM2.5-induced lung injury rats and rat alveolar macrophages (NR8383 cells). Methods The pneumotoxicity model was established by intratracheal injection of PM2.5 in rats, and PM2.5 challenge in NR8383 cells. The severity of lung injury was evaluated by wet weight to dry weight ratio and McGuigan pathology scoring. Inflammatory factors and oxidative stress were detected through ELISA. The expressions of p-PI3K, p-Akt, and p-mTOR proteins were analyzed by immunohistochemistry. Immunofluorescence and transmission electron microscopy were used to detect autophagosomes. The expressions of autophagy marker protein (LC3B and p62), PI3K/Akt/mTOR signaling and NF-κB translocation were detected by Western blot in lung tissue and NR8383 cells. Results After PM2.5 stimulation, rats showed severe inflammation and oxidative stress, along with inhibition of autophagy in lung tissue. AS-IV not only decreased pulmonary inflammation and oxidative stress by inhibiting nuclear factor kappa B translocation, but also regulated autophagy by inhibiting PI3K/Akt/mTOR signaling. After treatment with 3-methyladenine (a classic PI3K inhibitor, blocking the formation of autophagosomes), the protective effect of AS-IV on PM2.5-induced lung injury was further strengthened. In parallel, using Western blot, immunohistochemistry, and transmission electron microscopy, we demonstrated that AS-IV restore autophagic flux mainly through regulating the degradation of autophagosomes rather than suppressing the formation in vivo and in vitro. Conclusion Our data indicated that AS-IV protects from PM2.5-induced lung injury in vivo and in vitro by inhibiting the PI3K/Akt/mTOR pathway to regulate autophagy and inflammation.

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“…ID: “Silica dust exposure induces autophagy in alveolar macrophages through switching Beclin1 affinity from Bcl-2 to PIK3C3” [ 175 ]…”

Section: Commonality Of Contributing Factors Between Ibd and Id - Detailsmentioning

confidence: 99%

Common contributing factors to COVID-19 and inflammatory bowel disease

Kostoff

Briggs²,

Kanduc

et al. 2021

Toxicology Reports

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

Cited by 14 publications

References 44 publications

Targeting autophagy to overcome drug resistance: further developments

Targeting autophagy to overcome drug resistance: further developments

Astragaloside IV Protects from PM2.5-Induced Lung Injury by Regulating Autophagy via Inhibition of PI3K/Akt/mTOR Signaling in vivo and in vitro

Common contributing factors to COVID-19 and inflammatory bowel disease

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