Gold nanoparticles induce heme oxygenase-1 expression through Nrf2 activation and Bach1 export in human vascular endothelial cells

Abstract

It has been reported that increased levels and activity of the heme oxygenase-1 (HO-1) protein ameliorate tissue injuries. In the present study, we investigated the effects and mechanisms of action of gold nanoparticles (AuNPs) on HO-1 protein expression in human vascular endothelial cells (ECs). The AuNPs induced HO-1 protein and mRNA expression in a concentration- and time-dependent manner. The induction was reduced by the thiol-containing antioxidants, including N-acetylcysteine and glutathione, but not by the non-thiol-containing antioxidants and inhibitors that block the enzymes for intracellular reactive oxygen species generation. The AuNPs enhanced Nrf2 protein levels but did not affect Nrf2 mRNA expression. In response to the AuNP treatment, the cytosolic Nrf2 translocated to the nucleus, and, concomitantly, Bach1 exited the nucleus and its tyrosine phosphorylation increased. The chromatin immunoprecipitation assay revealed that the translocated Nrf2 bound to the antioxidant-response element located in the E2 enhancer region of the HO-1 gene promoter and acted as a transcription factor. Although N-acetylcysteine inhibited the AuNP-induced Nrf2 nuclear translocation, the AuNPs did not promote intracellular reactive oxygen species production or endoplasmic reticulum stress in the ECs. Knockdown of Nrf2 expression by RNA interference significantly inhibited AuNP-induced HO-1 expression at the protein and mRNA levels. In summary, AuNPs enhance the levels and nuclear translocation of the Nrf2 protein and Bach1 export/tyrosine phosphorylation, leading to Nrf2 binding to the HO-1 E2 enhancer promoter region to drive HO-1 expression in ECs. This study, together with our parallel findings, demonstrates that AuNPs can act as an HO-1 inducer, which may partially contribute to their anti-inflammatory bioactivity in human vascular ECs.

Connective tissue growth factor mediates transforming growth factor β-induced collagen expression in human endometrial stromal cells

“…The cell lysates were prepared as previously described [24]. The total proteins were analyzed by electrophoresis, blotted onto PVDF membranes, and then probed using an Ab raised against the indicated protein.…”

“…Oligonucleotide polymerase chain reaction (PCR) primers targeting human collagen, CTGF, HSP47, and β-actin were synthesized (Table 1). The total RNA extraction, reverse transcription of total RNA to cDNA, and PCR analysis have been previously described [24]. The PCR was performed with 30 cycles of denaturation at 94°C for 1 min, annealing at 52°C for 1 min, and elongation at 72°C for 1.5 min on the ABI 7200 Thermal Cycler (Applied Biosystems, Foster City, CA, USA).…”

Anti-Inflammatory Effect of Gold Nanoparticles Supported on Metal Oxides 

“…Indeed, gold colloids have been thought to cure various diseases for many centuries, and recent studies have demonstrated that this effect is mediated by inhibition of NF-B activation 10 . Different studies showed a similar effect in the case of Au NPs in vitro and in vivo, this effect being usually mediated by antioxidant properties 11,12,13,14,15 . However, other studies showed opposite results.…”

“…Gold (Au) can be deposited as nanoparticles (NPs) smaller than 10 nm in diameter on a variety of metal oxide (MOx) NPs. Au/MOx NPs have attracted much attention due to their high catalytic performance for such as room temperature CO oxidation and selective oxidations in liquid phase 12 .…”

Effect of Gold Nanoparticle on 5-Fluorouracil-Induced Experimental Oral Mucositis in Hamsters

“…Research shows that AuNp may be involved in regulating the KEAP1 (Kelch ECH-associated protein 1)-NRF2 (nuclear factor erythroid 2-related factor 2) pathway, and adjusting the cytoprotective response to endogenous and exogenous stress caused by reactive oxygen species (ROS) [46]. Under baseline conditions, the KEAP1 repressor protein binds to the inactive NRF2 factor present in the cytoplasm.…”