Gold nanoparticles reduce high glucose-induced oxidative-nitrosative stress regulated inflammation and apoptosis via tuberin-mTOR/NF-κB pathways in macrophages

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.

Increased miR-21-3p in Injured Brain Microvascular Endothelial Cells after Traumatic Brain Injury Aggravates Blood–Brain Barrier Damage by Promoting Cellular Apoptosis and Inflammation through Targeting MAT2B

“…Specifically, MAT2B can alleviate apoptosis in various tumor cells. [51][52][53] In addition, overexpression of MAT2B is associated with the inhibition of mTOR, 54 which is a classic upstream promoter of NF-jB signaling, 55,56 suggesting that MAT2B may alleviate cellular apoptosis and NF-jB signaling controlled inflammatory response. Consequently, our research fully identified that miR-21-3p could aggravate BBB damage after TBI by promoting cellular apoptosis and inflammation through targeting MAT2B.…”

NFκB and Kidney Injury

“…There are also new and emerging therapeutic opportunities with nanoparticles. For example, in hyperglycemia, gold nanoparticles reduce inflammation and apoptosis through tuberin-mTOR/ NFκB pathway inhibition in macrophages (149). In cancer cells, Zn-CuO nanoparticles can induce autophagy and apoptosis through the NFκB pathway (150).…”

Study on the levels of glycosylated lipoprotein in patients with coronary artery atherosclerosis

“…On the other hand, hyperglycemia can cause nonenzymatic reactions of glucose with longer‐lived molecules, resulting in stable early glycosylation products. Then, they undergo a series of rearrangements, dehydration, and cleavage reactions to produce stable glycation end products, including G‐LDL, G‐HDL, and other glycosylated proteins . Glycosylated lipoprotein also promotes lipoprotein oxidation .…”