REDD1 (regulated in development and DNA damage-1)/autophagy inhibition ameliorates fine particulate matter (PM2.5) -induced inflammation and apoptosis in BEAS-2B cells

Li, Yan; Xu, Xiaoxiao; Wang, Liyan; Li, Xuemei; Liu, Running; Zhang, Li; Xu, Yali

doi:10.1080/21655979.2021.1917227

Cited by 12 publications

(6 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The cell death shown in RTEC injury, which is an excellent feature of DN, is characterized by apoptosis. Accumulating evidence demonstrates that the inhibited REDD1 expression not only induced apoptosis of human umbilical vein endothelial cells after exposure to LPS, but also noticeably alleviated PM2.5-induced BEAS-2B cell apoptosis [ 21 , 34 ]. A study reported that REDD1 overexpression is sufficient to promote neuronal apoptosis [ 35 ].…”

Section: Discussionmentioning

confidence: 99%

Blocking REDD1/TXNIP Complex Ameliorates HG-Induced Renal Tubular Epithelial Cell Apoptosis and EMT through Repressing Oxidative Stress

Lin

Chen

et al. 2022

International Journal of Endocrinology

View full text Add to dashboard Cite

Diabetic nephropathy (DN) has become the most common secondary kidney disease causing end-stage renal disease (ESRD). Nevertheless, the underlying mechanisms responsible for DN remain largely unknown. Regulated in development and DNA damage response 1 (REDD1) is a prooxidative molecule known to contribute to diabetes mellitus and its complications. However, it has not been previously examined whether and how REDD1 can further drive renal tubular epithelial cell (RTEC) apoptosis and epithelial-to-mesenchymal transition in DN. The expression of REDD1 was elevated in the kidneys of DN patients and diabetic mice in this study. By generating the DN model in REDD1 knockout mice, we demonstrated that REDD1 deficiency significantly improved apoptosis and EMT in diabetic mice. In vitro experiments showed that REDD1 generation was induced by high glucose (HG) in HK-2 cells. Similarly, the transfection of REDD1 siRNA plasmid also suppressed HG-induced apoptosis and EMT. Furthermore, we discovered that the inhibition of REDD1 suppressed the expression of Nox4-induced HG and reactive oxygen species (ROS) synthesis in HK-2 cells. In addition, HG could induce endogenous REDD1 and TXNIP to form a powerful complex. In summary, our findings demonstrate that blocking the REDD1/TXNIP complex can prevent HG-induced apoptosis and EMT by inhibiting ROS production, highlighting REDD1 as a valuable therapeutic priority site for DN.

show abstract

Section: Discussionmentioning

confidence: 99%

Blocking REDD1/TXNIP Complex Ameliorates HG-Induced Renal Tubular Epithelial Cell Apoptosis and EMT through Repressing Oxidative Stress

Lin

Chen

et al. 2022

International Journal of Endocrinology

View full text Add to dashboard Cite

show abstract

“…After being fixed in 4% paraformaldehyde for 15 min, cell apoptosis was tested in accordance with the instructions of a TUNEL Apoptosis Detection kit (Beyotime, Shanghai, China) under the operation guidelines provided by the manufacturer [ 28 ]. After being centrifuged and washed for twice with phosphate buffer saline (PBS), cells were fixed with 4% paraformaldehyde for 30 min.…”

Section: Methodsmentioning

confidence: 99%

Octreotide activates autophagy to alleviate lipopolysaccharide-induced human pulmonary epithelial cell injury by inhibiting the protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway

2021

View full text Add to dashboard Cite

Octreotide is a synthetic octapeptide of natural somatostatin. We aimed to investigate the influence of Octreotide on lipopolysaccharide (LPS)-stimulated human pulmonary epithelial cell damage. After stimulated by LPS, BEAS-2B cells were treated with various concentrations of Octreotide. CCK-8 assay and LDH kits were to evaluate cell cytotoxicity. ELISA kits were to analyze the levels of inflammatory factors. TUNEL staining was to measure cell apoptosis. Western blot assay was used to assess the expression of apoptosis-related proteins, autophagy-related proteins and AKT/mTOR signaling-related proteins. Then, 3-methyladenine (3-MA) was adopted for treating BEAS-2B cells to determine its effects on inflammation and apoptosis. Afterward, adding AKT agonist (SC79) or mTOR antagonist (rapamycin) to explore the impact of Octreotide on autophagy. Results revealed that Octreotide notably enhanced cell viability and reduced LDH activity. The levels of inflammatory factors were significantly decreased following Octreotide treatment. Additionally, Octreotide attenuated the apoptotic capacity of LPS-induced BEAS-2B cells, led to the up-regulation of Bcl-2 protein level while cut down the protein levels of Bax and cleaved caspase3. Remarkably, the expression of autophagy-related protein LC3II/I and Beclin1 was elevated after Octreotide administration. Importantly, the suppressive effects of Octreotide on the inflammation and apoptosis of LPS-induced BEAS-2B cells was abrogated by 3-MA. Further experiments suggested that Octreotide downregulated p-AKT and mTOR expression in LPS-stimulated BEAS-2B cells. SC79 addition inhibited autophagy, evidenced by downregulated LC3II/I and Beclin1 expression while rapamycin presented the opposite effects. To conclude, Octreotide activates autophagy to alleviate LPS-induced pulmonary epithelial cell injury by inhibiting the AKT/mTOR signaling.

show abstract

“…Different concentrations of resveratrol solution were added to the cell culture medium in the dish to keep a final concentration of DMSO less than 0.1% in the culture medium. Then, the cytotoxicity test in the mHSCs after different concentrations of PM 2.5 (0, 1, 5, 10, 25, 50, 100, 200, 250, 500 µg/mL) and RES (0, 1, 2.5, 5, 10, 20, 50, 100 and 200 µmol/mL) was performed according to the previous study [17] and the instructions of the CCK8 assay kit (Beyotime Biotechnology, Shanghai, China). In brief, we prepared a mixture solution by combining cell culture medium and CCK-8 solution at a volume ratio of 10:1.…”

Section: Assessment Of Cytotoxicitymentioning

confidence: 99%

Protective Effects of Resveratrol on Cytotoxicity of Mouse Hepatic Stellate Cells Induced by PM2.5

Zhang,

Chen,

Bai

et al. 2024

Atmosphere

View full text Add to dashboard Cite

The atmosphere’s fine particulate matter (PM2.5) can enter the liver through the circulatory system, leading to hepatic inflammation and fibrosis. As a non-flavonoid polyphenolic compound, resveratrol (RES) has anti-oxidant, anti-inflammatory and hepatoprotective effects, but the molecular mechanisms of liver fibrosis induced by PM2.5 exposure are still limited. In this study, we established an in vitro cell model to investigate the intervention effect of RES with different concentrations (5 and 20 μmol/mL) on mouse hepatic stellate cells (mHSCs) injury induced by PM2.5 (100 μg/mL). We determined the cell viability in mHSCs after treatment with PM2.5 or/and RES for 24 h. We investigated the intracellular oxidative stress by detecting the changes in reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD) and lactate dehydrogenase (LDH) levels. We also measured the protein expressions of fibrosis-related genes (α-SMA, Collagen I and Collagen III) and key genes (SIRT1, NF-κB, NLRP3, Cleaved-Caspase1, IL-1β) in the NLRP3 pathway in mHSCs exposed to PM2.5 with or without RES. The results showed that (1) PM2.5 has cytotoxic effects on mHSCs, whereas RES (5 μmol/L and 20 μmol/L) inhibited PM2.5-induced cytotoxicity and LDH leakage; (2) RES effectively reduces ROS and MDA production caused by PM2.5 while concurrently enhancing SOD levels, thereby improving cellular anti-oxidant capacity; (3) the expression of α-SMA, Collagen I and Collagen III were notably downregulated in the PM2.5 plus RES treatment group compared to the PM2.5-exposed group; (4) RES significantly increased SIRT1 expression and decreased the expression of NF-κB, NLRP3, Cleaved-Caspase1 and IL-1β in mHSCs exposure to PM2.5 compared to the PM2.5 group. These results demonstrate that RES can up-regulate SIRT1 and mitigate PM2.5-induced fibrosis by suppressing oxidative stress in mHSCs and the SIRT1/NF–κB/NLRP3 pathway activated by PM2.5.

show abstract

REDD1 (regulated in development and DNA damage-1)/autophagy inhibition ameliorates fine particulate matter (PM2.5) -induced inflammation and apoptosis in BEAS-2B cells

Cited by 12 publications

References 35 publications

Blocking REDD1/TXNIP Complex Ameliorates HG-Induced Renal Tubular Epithelial Cell Apoptosis and EMT through Repressing Oxidative Stress

Blocking REDD1/TXNIP Complex Ameliorates HG-Induced Renal Tubular Epithelial Cell Apoptosis and EMT through Repressing Oxidative Stress

Octreotide activates autophagy to alleviate lipopolysaccharide-induced human pulmonary epithelial cell injury by inhibiting the protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway

Protective Effects of Resveratrol on Cytotoxicity of Mouse Hepatic Stellate Cells Induced by PM2.5

Contact Info

Product

Resources

About