Oxidative stress is well documented to cause injury to endothelial cells (ECs), which in turn trigger cardiovascular diseases. Previous studies revealed that cerium oxide nanoparticles (nanoceria) had antioxidant property, but the protective effect of nanoceria on ROS injury to ECs and cardiovascular diseases has not been reported. In the current study, we investigated the protective effect and underlying mechanisms of nanoceria on oxidative injury to ECs. The cell viability, lactate dehydrogenase release, cellular uptake, intracellular localization and reactive oxygen species (ROS) levels, endocytosis mechanism, cell apoptosis, and mitochondrial membrane potential were performed. The results indicated that nanoceria had no cytotoxicity on ECs but had the ability to prevent injury by H2O2. Nanoceria could be uptaken into ECs through caveolae- and clathrin-mediated endocytosis and distributed throughout the cytoplasma. The internalized nanoceria effectively attenuated ROS overproduction induced by H2O2. Apoptosis was also alleviated greatly by nanoceria pretreatment. These results may be helpful for more rational application of nanoceria in biomedical fields in the future.

Objective-The liver X receptors (LXRs) regulate a set of genes involved in lipid metabolism and reverse cholesterol transport. We investigated the mechanism by which shear stress regulates LXR in vascular endothelial cells (ECs). Methods and Results-Western blot showed that the protein level of LXR␣ and its target ABCA1 in the mouse thoracic aorta was higher than that in the aortic arch. As well, the mRNA level of LXR and its target genes ABCA1, ABCG1, ApoE, and LPL in the thoracic aorta was higher. In vitro, bovine aortic ECs were subjected to a steady laminar flow (12 dyne/cm 2 ). The expressions of LXR and the LXR-mediated transcription were increased by laminar shear stress. Laminar flow increased LXR-ligand binding and the gene expression of sterol 27-hydroxylase (CYP27), which suggests an increased level of LXR ligand in ECs. This effect was attenuated by LXR␣ and CYP27 RNAi. The decrease of LXR in the aorta of PPAR␥ ϩ/Ϫ mice and that of C57 mice fed with PPAR␥ antagonist suggest the involvement of PPAR␥ in the LXR induction by flow. Laminar shear stress in the straight parts of the arterial tree enhances vascular functioning, including the regulation of vascular tone, inhibition of cell proliferation and thrombosis, and augmentation of antiinflammatory effects. In contrast, disturbed flows with large oscillation near bifurcations and curvatures are considered proatherogenic. Thus, laminar shear stress is atheroprotective, whereas disturbed flow patterns are atheroprone. At the molecular and cellular levels, endothelial cells (ECs) have distinct mechanotransduction mechanisms responding to laminar versus disturbed flow patterns, which predispose the vessel wall to other chemical atherogenic factors. [3][4][5][6][7] In vitro flow channel experiments have revealed the atherprotection of steady laminar flow through promoting the expression of antioxidative and antiinflammatory genes, antiapoptosis, and EC cycle arrest. 8 -10 Histochemical and biochemical study has led to the hypothesis that impaired lipid homeostasis in the vessel wall induces the accumulation of low-density lipoprotein (LDL) and its metabolic products in the subendothelial space, macrophages, and vascular smooth muscle cells, thus leading to intimal thickening and plaque formation. 11 However, the mechanism by which local flow patterns cause impaired lipid homeostasis is still unclear. Conclusion-LaminarBelonging to the nuclear receptor superfamily, the liver X receptors (LXRs), including LXR␣ and LXR␤, play central roles in the transcriptional regulation of genes that participate in reverse cholesterol transport and lipid metabolism. Synthetic LXR agonists promote cholesterol efflux and inhibit the development of atherosclerosis in mice. 12-14 Administering a synthetic LXR ligand to ApoE Ϫ/Ϫ and LDLR Ϫ/Ϫ mice decreased lesion size by approximately 50%. 14 The transplantation of bone marrow from LXR␣␤ Ϫ/Ϫ mice to ApoE Ϫ/Ϫ or LDLR Ϫ/Ϫ recipient mice resulted in a marked increase in lesion size. 13 These results strongly support the notion t...

Nucleic acid-dependent ATPases are involved in nearly all aspects of DNA and RNA metabolism. Previous studies have described a number of mitochondrial helicases. However, double-stranded DNA-dependent ATPases, including translocases or enzymes remodeling DNA-protein complexes, have not been identified in mitochondria of the yeast Saccharomyces cerevisae. Here, we demonstrate that Irc3p is a mitochondrial double-stranded DNA-dependent ATPase of the Superfamily II. In contrast to the other mitochondrial Superfamily II enzymes Mss116p, Suv3p and Mrh4p, which are RNA helicases, Irc3p has a direct role in mitochondrial DNA (mtDNA) maintenance. Specific Irc3p-dependent mtDNA metabolic intermediates can be detected, including high levels of double-stranded DNA breaks that accumulate in irc3Δ mutants. irc3Δ-related topology changes in rho- mtDNA can be reversed by the deletion of mitochondrial RNA polymerase RPO41, suggesting that Irc3p counterbalances adverse effects of transcription on mitochondrial genome stability.

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