International Journal of Nanomedicine (Aug 2017)
Gold nanoparticles reduce high glucose-induced oxidative-nitrosative stress regulated inflammation and apoptosis via tuberin-mTOR/NF-κB pathways in macrophages
Abstract
Huma Rizwan,1 Jagdeep Mohanta,2 Satyabrata Si,1,2 Arttatrana Pal3 1School of Biotechnology, KIIT University, Bhubaneswar, India; 2School of Applied Sciences, KIIT University, Bhubaneswar, India; 3Department of Zoology, School of Life Sciences, Mahatma Gandhi Central University, Bihar, India Abstract: Hyperglycemia is a risk factor for cardiovascular mortality and morbidity, and directly responsible for exacerbating macrophage activation and atherosclerosis. We showed that gold nanoparticles (AuNPs) reduce the high glucose (HG)-induced atherosclerosis-related complications in macrophages via oxidative-nitrosative stress-regulated inflammation and apoptosis. The effects of AuNPs on oxidative-nitrosative stress markers such as cellular antioxidants were attenuated by HG exposure, leading to reduction in the accumulation of reactive oxygen/nitrogen species in cellular compartments. Further, these abnormalities of antioxidants level and reactive oxygen/nitrogen species accumulations initiate cellular stress, resulting in the activation of nuclear factor κB (NF-κB) via ERK1/2mitogen-activated protein kinase (MAPK)/Akt/tuberin- mammalian target of rapamycin (mTOR) pathways. The activated NF-κB stimulates inflammatory mediators, which subsequently subdue biomolecules damage, leading to aggravation of the inflammatory infiltration and immune responses. Treatment of AuNPs inhibits the intracellular redox-sensitive signaling pathways, inflammation, and apoptosis in macrophages. Together, our results indicate that AuNPs may modulate HG-induced oxidative-nitrosative stress. These effects may be sealed tight due to the fact that AuNPs treatment reduces the activation of NF-κB by ERK1/2MAPK/Akt/tuberin-mTOR pathways-mediated inflammatory genes expression and cellular stress responses, which may be beneficial for minimizing the atherosclerosis. Keywords: gold nanoparticles, oxidative-nitrosative stress, apoptosis, macrophages, atherosclerosis