RESUMO
Four-and-a-half LIM domains protein 2 (FHL2) is an adaptor protein that may interact with hypoxia inducible factor 1α (HIF-1α) or ß-catenin, two pivotal protective signaling in acute kidney injury (AKI). However, little is known about the regulation and function of FHL2 during AKI. We found that FHL2 was induced in renal tubular cells in patients with acute tubular necrosis and mice model of ischemia-reperfusion injury (IRI). In cultured renal proximal tubular cells (PTCs), hypoxia induced FHL2 expression and promoted the binding of HIF-1 to FHL2 promoter. Compared with control littermates, mice with PTC-specific deletion of FHL2 gene displayed worse renal function, more severe morphologic lesion, more tubular cell death and less cell proliferation, accompanying by downregulation of AQP1 and Na, K-ATPase after IRI. Consistently, loss of FHL2 in PTCs restricted activation of HIF-1 and ß-catenin signaling simultaneously, leading to attenuation of glycolysis, upregulation of apoptosis-related proteins and downregulation of proliferation-related proteins during IRI. In vitro, knockdown of FHL2 suppressed hypoxia-induced activation of HIF-1α and ß-catenin signaling pathways. Overexpression of FHL2 induced physical interactions between FHL2 and HIF-1α, ß-catenin, GSK-3ß or p300, and the combination of these interactions favored the stabilization and nuclear translocation of HIF-1α and ß-catenin, enhancing their mediated gene transcription. Collectively, these findings identify FHL2 as a direct downstream target gene of HIF-1 signaling and demonstrate that FHL2 could play a critical role in protecting against ischemic AKI by promoting the activation of HIF-1 and ß-catenin signaling through the interactions with its multiple protein partners.
Assuntos
Injúria Renal Aguda , Túbulos Renais Proximais , Proteínas com Homeodomínio LIM , Proteínas Musculares , Traumatismo por Reperfusão , Fatores de Transcrição , beta Catenina , Animais , Proteínas com Homeodomínio LIM/metabolismo , Proteínas com Homeodomínio LIM/genética , Proteínas Musculares/metabolismo , Proteínas Musculares/genética , Injúria Renal Aguda/metabolismo , Injúria Renal Aguda/patologia , Injúria Renal Aguda/genética , Humanos , Túbulos Renais Proximais/metabolismo , Túbulos Renais Proximais/patologia , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia , Traumatismo por Reperfusão/genética , Camundongos , beta Catenina/metabolismo , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Masculino , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Transdução de Sinais , Camundongos Endogâmicos C57BL , Camundongos Knockout , Glicogênio Sintase Quinase 3 beta/metabolismo , Glicogênio Sintase Quinase 3 beta/genética , Proliferação de Células , ApoptoseRESUMO
We report the first proof of concept for a nonaqueous, all-organic semisolid flow battery (SSFB) using suspensions of 10-methylphenothiazine@Ketjen black and thioxanthone@Ketjen black dispersed in tetraethylammonium hexafluorophosphate/acetonitrile as the cathode and anode, respectively. A proof of principle cell with an open circuit voltage of 2.35 V demonstrated an average coulombic efficiency of 83% within the voltage range 3.0-0 V. This study provides a potential path for developing new high energy density and cost-effective nonaqueous organic SSFBs.
RESUMO
An all organic redox flow battery with 4,4'-dimethylbenzophenone (44DMBP) anolyte and 2,5-di-tert-butyl-1,4-dimethoxybenzene (DBB) catholyte shows a high open circuit voltage of 2.97 V, and average coulombic efficiency of 72% over 95 cycles at a current density of 1 mA cm-2.
RESUMO
Benzophenone and 1,4-di-tert-butyl-2,5-dimethoxybenzene are used as the anode and cathode active species respectively in an all-organic redox-flow battery. A number of organics as the co-solvents are applied in the electrolyte to improve the electrochemical performance of it. For all kinds of the mixed solvents, a lower content of acetonitrile leads to a higher solubility to 1,4-di-tert-butyl-2,5-dimethoxybenzene and a lower conductivity. The results of cyclic voltammetry tests demonstrate that the electrode reactions are controlled by diffusion. With the decrease of the content of acetonitrile, the dynamic viscosity of the electrolyte increases, which generally leads to the decrease of the diffusion coefficients of the active species.