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10.3109/17435390.2014.991430 http://scihub22266oqcxt.onion/10.3109/17435390.2014.991430 25676618!ä!25676618 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 245.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 245.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Nanotoxicology 2015 ; 9 (7): 905-17 Nephropedia Template TP {{tp|p=25676618|t=2015. Importance of the HIF pathway in cobalt nanoparticle-induced cytotoxicity and inflammation in human macrophages |pdf=|usr=}}{{25676618}} gab.com Text Importance of the HIF pathway in cobalt nanoparticle-induced cytotoxicity and inflammation in human macrophages JO: Nanotoxicology http://www.kidney.de/pget.php?&tw=1&pmid=25676618 #FOAvip Recent, unexpected high failure rates of metal-on-metal hip implants have reintroduced the issue of cobalt toxicity. An adverse reaction to cobalt ions and cobalt-induced lung injury occurs during environmental exposure and is now strictly controlled. Currently adverse reaction occurs to cobalt nanoparticles during wear and tear of metal-on-metal hip implants of which the underlying mechanism is not fully understood. The putative role of the hypoxia-inducible factor (HIF) pathway in the mechanism of cobalt nanoparticle (Co-NPs) toxicity was examined using the U937 cell line, human alveolar macrophages and monocyte-derived macrophages. Co-NPs (5-20 mug/ml)-induced cytotoxicity (viability ranged from 75% to <20% of control, respectively) and reactive oxygen species (ROS), whereas a comparable concentration of cobalt ions (Co(II); up to 350 muM) did not. Co-NPs induced HIF-1alpha stabilization. Addition of ascorbic acid (100 microM) and glutathione (1 mM) both prevented the increased ROS. However, only treatment with ascorbic acid reduced HIF-1alpha levels and prevented cell death, indicating that a ROS-independent pathway is involved in Co-NPs-induced cytotoxicity. Replenishing intracellular ascorbate, which is crucial in preventing HIF pathway activation, modified Co-induced HIF target gene expression and the inflammatory response, by decreasing interleukin-1 beta (IL-1beta) mRNA and protein expression. Addition of glutathione had no effect on Co-NPs-induced HIF target gene expression or inflammatory response. Thus, Co-NPs induce the HIF pathway by depleting intracellular ascorbate, leading to HIF stabilization and pathway activation. This suggests a strong, ROS-independent role for HIF activation in Co-NPs-induced cytotoxicity and a possible role for HIF in metal-on-metal hip implant pathology. Twit Text FOAVip Importance of the HIF pathway in cobalt nanoparticle-induced cytotoxicity and inflammation in human macrophages ????Nanotoxicology http://www.kidney.de/pget.php?&tw=1&pmid=25676618 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=25676618 #FOAvip English Wikipedia <ref>{{Cite pmid|25676618}}</ref> Importance of the HIF pathway in cobalt nanoparticle-induced cytotoxicity and inflammation in human macrophages #MMPMID25676618 Nyga A; Hart A; Tetley TD Nanotoxicology 2015[]; 9 (7): 905-17 PMID25676618show ga Recent, unexpected high failure rates of metal-on-metal hip implants have reintroduced the issue of cobalt toxicity. An adverse reaction to cobalt ions and cobalt-induced lung injury occurs during environmental exposure and is now strictly controlled. Currently adverse reaction occurs to cobalt nanoparticles during wear and tear of metal-on-metal hip implants of which the underlying mechanism is not fully understood. The putative role of the hypoxia-inducible factor (HIF) pathway in the mechanism of cobalt nanoparticle (Co-NPs) toxicity was examined using the U937 cell line, human alveolar macrophages and monocyte-derived macrophages. Co-NPs (5-20 mug/ml)-induced cytotoxicity (viability ranged from 75% to <20% of control, respectively) and reactive oxygen species (ROS), whereas a comparable concentration of cobalt ions (Co(II); up to 350 muM) did not. Co-NPs induced HIF-1alpha stabilization. Addition of ascorbic acid (100 microM) and glutathione (1 mM) both prevented the increased ROS. However, only treatment with ascorbic acid reduced HIF-1alpha levels and prevented cell death, indicating that a ROS-independent pathway is involved in Co-NPs-induced cytotoxicity. Replenishing intracellular ascorbate, which is crucial in preventing HIF pathway activation, modified Co-induced HIF target gene expression and the inflammatory response, by decreasing interleukin-1 beta (IL-1beta) mRNA and protein expression. Addition of glutathione had no effect on Co-NPs-induced HIF target gene expression or inflammatory response. Thus, Co-NPs induce the HIF pathway by depleting intracellular ascorbate, leading to HIF stabilization and pathway activation. This suggests a strong, ROS-independent role for HIF activation in Co-NPs-induced cytotoxicity and a possible role for HIF in metal-on-metal hip implant pathology. |Ascorbic Acid/pharmacology[MESH] |Cell Death/*drug effects[MESH] |Cells, Cultured[MESH] |Cobalt/chemistry/*toxicity[MESH] |Dose-Response Relationship, Drug[MESH] |Glutathione/pharmacology[MESH] |Humans[MESH] |Hypoxia-Inducible Factor 1, alpha Subunit/*metabolism[MESH] |Inflammation/chemically induced/*metabolism[MESH] |Macrophages/*drug effects/metabolism[MESH] |Nanoparticles/chemistry/*toxicity[MESH] |Reactive Oxygen Species/metabolism[MESH]Importance of the HIF pathway in cobalt nanoparticle-induced cytotoxic(epmc).pdf DeepDyve Pubget Overpricing