Activation of Nrf2/HO‐1 signaling pathway attenuates ROS‐mediated autophagy induced by silica nanoparticles in H9c2 cells

Abstract

Silica nanoparticles (SiNPs) as one of the most productive nano‐powder, has been extensively applied in various fields. There has been increasing concern about the adverse effects of SiNPs on the health of ecological organisms and human. The potential cardiovascular toxicity of SiNPs and involved mechanisms remain elusive. Hence, in this study, we investigated the cardiovascular toxicity of SiNPs (60 nm) and explored the underlying mechanisms using H9c2 cardiomyocytes. Results showed that SiNPs induced oxidative stress and activated the Nrf2/HO‐1 antioxidant pathway. Autophagy was also activated by SiNPs. Interestingly, N‐acetyl‐L‐cysteine (NAC）attenuated autophagy after inhibiting reactive oxygen species (ROS). Meanwhile, down‐regulation of Nrf2 enhanced autophagy. In summary, these data indicated that SiNPs induce autophagy in H9c2 cardiomyocytes through oxidative stress, and the Nrf2/HO‐1 pathway has a negative regulatory effect on autophagy. This study provides new evidence for the cardiovascular toxicity of SiNPs and provides a reference for the safe use of nanomaterials in the future.

Dexmedetomidine alleviates early brain injury following traumatic brain injury by inhibiting autophagy and neuroinflammation through the ROS/Nrf2 signaling pathway

“…The majority of these genes regulate oxidative stress and cell apoptosis, autophagy and ferroptosis ( 30 ). TBI leads to intracellular ROS accumulation and decreases the expression levels of Nrf2 and HO-1 and the Nrf2/HO-1 signaling pathway also directly regulates autophagy ( 56 ). In the present study, DEX decreased ROS levels and then downregulated Nrf2 and HO-1 expression in the experimental TBI model.…”

Silica Nanoparticles Promote the Megakaryocyte Maturation and Differentiation: Potential Implications for Hematological Homeostasis

“…The significant increases in the transcriptional levels of GATA-1 and FLI-1 (Figure ), and their positive correlation with the indicators for megakaryocyte maturation and differentiation in SiO 2 NP exposure groups (Figure B) confirmed the induction effect of this kind of NPs on megakaryocyte development through the regulation of these two genes. Nevertheless, the undisturbed transcription factor of NF-E2 in Dami cells upon SiO 2 NP stimulation was distinct from the findings in BEAS-2b and H9c2 cells, where the mRNA level of NF-E2 related factor 2 was altered by SiO 2 NP exposure. , This intricate transcriptional regulation of the SiO 2 NPs could be related with the cell type, and the upregulation of both GATA-1 and FLI-1 played the dominant role in SiO 2 NP-induced megakaryocyte maturation and differentiation.…”

“…Nevertheless, the undisturbed transcription factor of NF-E2 in Dami cells upon SiO 2 NP stimulation was distinct from the findings in BEAS-2b and H9c2 cells, where the mRNA level of NF-E2 related factor 2 was altered by SiO 2 NP exposure. 4,43 This intricate transcriptional regulation of the SiO 2 NPs could be related with the cell type, and the upregulation of both GATA-1 and FLI-1 played the dominant role in SiO 2 NP-induced megakaryocyte maturation and differentiation. As demonstrated previously, the anionic silica surface could attract positively charged peptides by ion pairing, and hydrogen bonds, as well as ion−dipole, dipole−dipole, and van der Waals interactions, could form between polar groups in the peptide of target proteins with silanol groups on the silica surface.…”

Evidence-Based Prediction of Cellular Toxicity for Amorphous Silica Nanoparticles

“…The final predictive models were used to predict the independent data sets derived from external studies published between 2017 and 2022. ,− Specifically, Gong et al (2017) exposed HaCaT cells to 15 nm SiO 2 -NPs for 24 h (nine samples). Similarly, Liu et al (2017) subjected A549 cells to 15 nm SiO 2 -NPs over a period of 24 h (eight samples), whereas Nishijima et al (2017) put 10–1000 nm SiO 2 -NPs in contact with THP-1 cells for 6–24 h (105 samples).…”

“…Tada-Oikawa et al (2020) subjected Caco-2 cells with 30 nm SiO 2 -NPs for 24 h (25 samples), and Wang et al (2020) observed the effects of 16.75 nm SiO 2 -NPs on BEAS-2B cells over periods of 24 and 48 h (10 samples). Similarly, Cui et al (2021) exposed H9c2 cells to 60 nm SiO 2 -NPs for 6–48 h (24 samples). The effects of exposing SH-SY5Y cells to 63 nm SiO 2 -NPs were examined for periods of 3–24 h (25 samples) by Hou et al (2021), while the influence of 16–51 nm SiO 2 -NPs on NRK cells for 24 h (12 samples) was investigated by Ruan et al (2021) .…”