Recombinant adenovirus Ad-RUNrf2 reduces paraquat-induced A549 injury

Cai, Qianqian; Lu, Zhongqiu; Hong, Guangliang; Xin, Jiang; Wu, Zhenzhou; Zheng, Jianjian; Song, Qingliang; Chang, Zhiqiang

doi:10.1177/0960327112450902

Cited by 8 publications

(8 citation statements)

References 23 publications

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“…Previous studies have revealed that SIRT1 promotes the activity of NRF2 and upregulates the expression of NRF2 downstream genes, such as SOD (14,15), and that the knockdown of SIRT1 results in the downregulation of NRF2 expression (16). In our previous SIRT1 exerts protective effects against paraquat-induced injury in mouse type II alveolar epithelial cells by deacetylating NRF2 in vitro study, we confirmed that NRF2 is activated and plays a role in protecting A549 lung cells against oxidative damage following exposure to PQ (17). However, the association between SIRT1 and NRF2, as well as their effects on PQ-induced oxidative stress remain to be elucidated.…”

Section: Introductionsupporting

confidence: 80%

SIRT1 exerts protective effects against paraquat-induced injury in mouse type II alveolar epithelial cells by deacetylating NRF2 in vitro

Ding

Zhao

et al. 2016

International Journal of Molecular Medicine

118

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Silent information regulator 2-related enzyme 1 (SIRT1), a protein deacetylase, is known to strongly protect cells against oxidative stress-induced injury. The nuclear factor E2-related factor 2 (NRF2)-antioxidant response element (ARE) antioxidant pathway plays important regulatory roles in the antioxidant therapy of paraquat (PQ) poisoning. In the present study, we investigated whether the SIRT1/NRF2/ARE signaling pathway plays an important role in lung injury induced by PQ. For this purpose, mouse type II alveolar epithelial cells (AECs‑II) were exposed to various concentrations of PQ. The overexpression or silencing of SIRT1 was induced by transfecting the cells with a SIRT1 overexpression vector or shRNA targeting SIRT1, respectively. The protein expression levels of SIRT1 and NRF2 were measured by western blot analysis. The superoxide dismutase (SOD) and catalase (CAT) activities, as well as the glutathione (GSH) and malondialdehyde (MDA) levels were measured using respective kits. Heme oxygenase-1 (HO-1) activity was also determined by ELISA. In addition, cell apoptosis was determined by flow cytometry. The protein stability of NRF2 was analyzed using cycloheximide and its acetylation in the cells was also determined. The following findings were obtained: i) SIRT1 overexpression markedly increased NRF2 protein expression; ii) SIRT1 promoted the transcriptional activity of NRF2 and upregulated the expression of the NRF2 downstream genes, SOD, CAT, GSH and HO-1, thus inhibiting the apoptosis of AECs‑II; iii) the inhibition of SIRT1 activity further induced the production of malondialdehyde (MDA), which resulted in increased oxidative damage; iv) SIRT1 promoted the stability of NRF2 by regulating the deacetylation and activation of the NRF2/ARE antioxidant pathway. The findings of this study demonstrate that the protective effects of SIRT1 are associated with the activation of the NRF2/ARE antioxidant pathway in lung injury induced by PQ poisoning.

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Section: Introductionsupporting

confidence: 80%

SIRT1 exerts protective effects against paraquat-induced injury in mouse type II alveolar epithelial cells by deacetylating NRF2 in vitro

Ding

Zhao

et al. 2016

International Journal of Molecular Medicine

118

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“…As shown in our previous study, an anti-IL-6 receptor antibody and an NF- κB inhibitor, caffeic acid phenethyl ester, reduce the titers of the A/H1N1 pdm 2009 virus [15]. Furthermore, IL-6 activates caspases [16] that enhance the release of viral ribonucleoprotein complexes from the nucleus [17]. In our previous study, a caspase-3 inhibitor, Z-DEVD-fmk, reduced the A/H1N1 pdm 2009 viral titers in the supernatants [15].…”

Section: Discussionmentioning

confidence: 57%

Effects of high temperature on pandemic and seasonal human influenza viral replication and infection-induced damage in primary human tracheal epithelial cell cultures

Yamaya

Nishimura

Kalonji

et al. 2019

Heliyon

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High temperature reduces influenza viral replication; however, the treatment of fevers is thought to be necessary to improve patients' conditions. We examined the effects of high temperature on viral replication and infection-induced damage to human tracheal epithelial cells. Cell viability and dome formation were reduced, the number of detached cells was increased and lactate dehydrogenase (LDH) levels tended to be increased from 72 h to 120 h in uninfected cells cultured at 40 °C. Long-term (72 h and/or 120 h) exposure to high temperatures (39 °C and/or 40 °C) decreased RNA levels and/or viral titers of eight influenza virus strains. Cell viability and dome formation were reduced, and the number of detached cells and LDH levels were increased to a similar extent after infection with the A/H1N1 pdm 2009 virus at 37 °C and 40 °C. High temperature increased the endosomal pH, where the viral RNA enters the cytoplasm, in uninfected cells. High temperature reduced the production of IL-6, which mediate viral replication processes, and IL-1β and IL-8 in uninfected and infected cells. Based on these findings, high temperature may cause similar levels of airway cell damage after infection to cells exposed normal temperatures, although high temperature reduces viral replication by affecting the function of acidic endosomes and inhibiting IL-6-mediated processes.

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“…Studies [18] have also shown that PQ poisoning can induce the release of inflammatory cytokines in human alveolar epithelial A549 cells, with increased expression of TNF- α , IL-1 β , and IL-6. In this study, a rat model of acute lung injury was constructed by PQ exposure.…”

Section: Discussionmentioning

confidence: 99%

Metformin Activates the Protective Effects of the AMPK Pathway in Acute Lung Injury Caused by Paraquat Poisoning

Cen

Feng

et al. 2019

Oxidative Medicine and Cellular Longevity

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Objective To observe whether metformin (MET) plays a protective role in acute lung injury (ALI) induced by paraquat (PQ) poisoning in rats by activating the AMPK/NF-κB signaling pathway. Methods PQ exposure was used to construct a rat model of ALI and a model of acute type II alveolar epithelial cell (RLE-6TN) injury, and MET intervention was performed. Rat lung tissue samples were collected to evaluate pathological changes in rat lung tissue, the oxidation index, and inflammatory factors; cell viability was detected by CCK-8 assays, and the protein expression levels of phospho-AMPK and phospho-NF-κBp65 in rat lung tissue and RLE-6TN cells were observed by Western blotting. Results Compared with the PQ group, the MET treatment group showed significantly (1) reduced lung wet/dry ratio (W/D: 4.67 ± 0.31 vs. 5.45 ± 0.40, P < 0.001), (2) reduced pathological changes in lung tissue, (3) decreased MDA levels (nmol/mg prot: 2.70 ± 0.19 vs. 3.08 ± 0.15, P < 0.001) and increased SOD and GSH-Px activities (U/mg prot: 76.17 ± 5.22 vs. 45.23 ± 6.58, 30.40 ± 2.84 vs. 21.00 ± 3.20; all P < 0.001) in lung tissue homogenate, (4) reduced levels of IL-1β, IL-6, and TNF-α in lung tissue homogenates (pg/mL: 47.87 ± 5.06 vs. 66.77 ± 6.55; 93.03 ± 7.41 vs. 107.39 ± 9.81; 75.73 ± 6.08 vs. 89.12 ± 8.94; all P < 0.001), (5) increased activity of RLE-6TN cells (%: 0.69 ± 0.09, 0.76 ± 0.06, and 0.58 ± 0.03 vs. 0.50 ± 0.05; all P < 0.05), (6) decreased protein levels of phospho-NF-κBp65 in lung homogenates and RLE-6TN cells (p-NF-κB/NF-κB: 0.47 ± 0.09 vs. 0.81 ± 0.13; 0.26 ± 0.07 vs. 0.79 ± 0.13; all P < 0.01), and (7) upregulated protein expression of phospho-AMPK in lung homogenates and RLE-6TN cells (p-AMPK/AMPK: 0.88 ± 0.05 vs. 0.36 ± 0.12; 0.93 ± 0.03 vs. 0.56 ± 0.15; all P < 0.01). After the addition of the AMPK inhibitor Compound C (Com C), the protein expression levels of phospho-AMPK and phospho-NF-κBp65 returned to baseline. Conclusion MET can effectively alleviate ALI induced by paraquat poisoning and increase the viability of cells exposed to paraquat. The mechanism may be related to the activation of the AMPK/NF-κB pathway, downregulation of inflammatory mediators such as IL-6 and TNF-α, and upregulation of the SOD and GSH-Px oxidation index, and these effects can be inhibited by the AMPK inhibitor Com C.

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Recombinant adenovirus Ad-RUNrf2 reduces paraquat-induced A549 injury

Abstract: Ad-RUNrf2 adenovirus was successfully constructed and can be stably expressed and regulated in cells. Ad-RUNrf2 can reduce PQ-induced inflammation, oxidative stress and apoptosis in A549 cells.

Cited by 8 publications

References 23 publications

SIRT1 exerts protective effects against paraquat-induced injury in mouse type II alveolar epithelial cells by deacetylating NRF2 in vitro

SIRT1 exerts protective effects against paraquat-induced injury in mouse type II alveolar epithelial cells by deacetylating NRF2 in vitro

Effects of high temperature on pandemic and seasonal human influenza viral replication and infection-induced damage in primary human tracheal epithelial cell cultures

Metformin Activates the Protective Effects of the AMPK Pathway in Acute Lung Injury Caused by Paraquat Poisoning

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