The potential applications of superparamagnetic iron oxide nanoparticles (SPIONs) in several nanomedical fields have attracted intense interest based on the cell-nano interaction. However, the mechanisms underlying cell uptake, the intracellular trail, final fate and the biological effects of SPIONs have not yet been clearly elucidated. Here, we showed that multiple endocytic pathways were involved in the internalization process of SPIONs in the RAW264.7 macrophage. The internalized SPIONs were biocompatible and used three different metabolic pathways: The SPIONs were distributed to daughter cells during mitosis; they were degraded in the lysosome and free iron was released into the intracellular iron metabolic pool; and, the intact SPIONs were potentially exocytosed out of the cells. The internalized SPIONs did not induce cell damage but affected iron metabolism, inducing the upregulation of ferritin light chain at both the mRNA and protein levels and ferroportin 1 at the mRNA level. These results may contribute to the development of nanobiology and to the safe use of SPIONs in medicine when administered as a contrast medium or a drug delivery tool.
Autoimmune activities have been implicated in the pathogenesis of hypertension.High levels of autoantibodies against the second extracellular loop of α1-adrenoceptor(α1-AR autoantibody,α1-AA) are found in patients with hypertension,and α1-AA could exert a α1-AR agonist-like vasoconstrictive effect.However,whether the vasoconstrictive effect of α1-AA is enhanced in hypertension is unknown.Using aortic rings of spontaneously hypertensive rats(SHR) and normotensive Wistar-Kyoto(WKY) rats,we observed the vasoconstrictive responses to α1-AA with phenylephrine(α1-AR agonist) as a positive control drug.Aortic nitrotyrosine levels were also measured by ELISA and immunohistochemistry.The results showed that the aortic constrictive responses to α1-AA and phenylephrine(both 1 nmol L-1-10 μmol L-1) were greater in SHR than in WKY rats.Endothelial denudation or L-NAME(a non-selective NOS inhibitor)(100 μmol L-1) increased α1-AA- or phenylephrine-induced vasoconstrictions both in SHR and WKY.However,selective iNOS inhibitor 1400W(10 μmol L-1) enhanced the α1-AA-induced aortic constriction in WKY,but not in SHR.The aortic nitrotyrosine level was significantly higher in SHR than WKY,as shown by both ELISA and immunohistochemistry.These results indicate that the vasoconstrictive response to α1-AA is enhanced in SHR,and this altered responsiveness is due to endothelial dysfunction and decreased NO bioavailability.The study suggests an important role of α1-AR autoimmunity in the pathogenesis and management of hypertension especially in those harboring high α1-AA levels.
YAN LiTAN XiaoQiuCHEN WenXuanZHU HongCAO JiMinLIU HuiRong
