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Thomas H Lee - One of the best experts on this subject based on the ideXlab platform.
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The Volatile Anesthetic Isoflurane Increases Endothelial Adenosine Generation via Microparticle Ecto-59- Nucleotidase (CD73) Release
2016Co-Authors: Mihwa Kim, Ahrom Ham, Kevin M Brown, Katelyn Yu-mi Kim, Thomas H LeeAbstract:Endothelial dysfunction is common in acute and chronic organ injury. Isoflurane is a widely used halogenated volatile anesthetic during the perioperative period and protects against endothelial cell death and inflammation. In this study, we tested whether Isoflurane induces endothelial ecto-59-nucleotidase (CD73) and cytoprotective adenosine generation to protect against endothelial cell injury. Clinically relevant concentrations of Isoflurane induced CD73 activity and increased adenosine generation in cultured human umbilical vein or mouse glomerular endothelial cells. Surprisingly, Isoflurane-mediated induction of endothelial CD73 activity occurred within 1 hr and without synthesizing new CD73. We determined that Isoflurane rapidly increased CD73 containing endothelial microparticles into the cell culture media. Indeed, microparticles isolated from Isoflurane-treated endothelial cells had significantly higher CD73 activity as well as increased CD73 protein. In vivo, plasma from mice anesthetized with Isoflurane had significantly higher endothelial cell-derived CD144+ CD73+ microparticles and had increased microparticle CD73 activity compared to plasma from pentobarbital-anesthetized mice. Supporting a critical role of CD73 in Isoflurane-mediated endothelial protection, a selective CD73 inhibitor (APCP) prevented Isoflurane-induced protection against human endothelial cell inflammation and apoptosis. In addition, Isoflurane activated endothelial cells Rho kinase evidenced by myosin phosphatase target subunit-1 and myosin light chain phosphorylation. Furthermore, Isoflurane-induced release of CD73 containing microparticles was significantl
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the volatile anesthetic Isoflurane increases endothelial adenosine generation via microparticle ecto 5 nucleotidase cd73 release
PLOS ONE, 2014Co-Authors: Mihwa Kim, Ahrom Ham, Kevin M Brown, Katelyn Yu-mi Kim, Thomas H LeeAbstract:Endothelial dysfunction is common in acute and chronic organ injury. Isoflurane is a widely used halogenated volatile anesthetic during the perioperative period and protects against endothelial cell death and inflammation. In this study, we tested whether Isoflurane induces endothelial ecto-5′-nucleotidase (CD73) and cytoprotective adenosine generation to protect against endothelial cell injury. Clinically relevant concentrations of Isoflurane induced CD73 activity and increased adenosine generation in cultured human umbilical vein or mouse glomerular endothelial cells. Surprisingly, Isoflurane-mediated induction of endothelial CD73 activity occurred within 1 hr and without synthesizing new CD73. We determined that Isoflurane rapidly increased CD73 containing endothelial microparticles into the cell culture media. Indeed, microparticles isolated from Isoflurane-treated endothelial cells had significantly higher CD73 activity as well as increased CD73 protein. In vivo, plasma from mice anesthetized with Isoflurane had significantly higher endothelial cell-derived CD144+ CD73+ microparticles and had increased microparticle CD73 activity compared to plasma from pentobarbital-anesthetized mice. Supporting a critical role of CD73 in Isoflurane-mediated endothelial protection, a selective CD73 inhibitor (APCP) prevented Isoflurane-induced protection against human endothelial cell inflammation and apoptosis. In addition, Isoflurane activated endothelial cells Rho kinase evidenced by myosin phosphatase target subunit-1 and myosin light chain phosphorylation. Furthermore, Isoflurane-induced release of CD73 containing microparticles was significantly attenuated by a selective Rho kinase inhibitor (Y27632). Taken together, we conclude that the volatile anesthetic Isoflurane causes Rho kinase-mediated release of endothelial microparticles containing preformed CD73 and increase adenosine generation to protect against endothelial apoptosis and inflammation.
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the volatile anesthetic Isoflurane induces ecto 5 nucleotidase cd73 to protect against renal ischemia and reperfusion injury
Kidney International, 2013Co-Authors: Mihwa Kim, Vivette D Dagati, Ahrom Ham, Joo Yun Kim, Kevin M Brown, Thomas H LeeAbstract:The volatile anesthetic Isoflurane protects against renal ischemia and reperfusion injury by releasing renal tubular TGF-β1. As adenosine is a powerful cytoprotective molecule, we tested whether TGF-β1 generated by Isoflurane induces renal tubular ecto-5′-nucleotidase (CD73) and adenosine to protect against renal ischemia and reperfusion injury. Isoflurane induced new CD73 synthesis and increased adenosine generation in cultured kidney proximal tubule cells and in mouse kidney. Moreover, a TGF-β1-neutralizing antibody prevented Isoflurane-mediated induction of CD73 activity. Mice anesthetized with Isoflurane after renal ischemia and reperfusion had significantly reduced plasma creatinine and decreased renal tubular necrosis, neutrophil infiltration, and apoptosis compared with pentobarbital-anesthetized mice. Isoflurane failed to protect against renal ischemia and reperfusion injury in CD73-deficient mice, in mice pretreated with a selective CD73 inhibitor, or in mice treated with an adenosine receptor antagonist. The TGF-β1-neutralizing antibody or the CD73 inhibitor attenuated Isoflurane-mediated protection against HK-2 cell apoptosis. Thus, Isoflurane causes TGF-β1-dependent induction of renal tubular CD73 and adenosine generation to protect against renal ischemia and reperfusion injury. Modulation of this pathway may have important therapeutic implications to reduce morbidity and mortality arising from ischemic acute kidney injury.
Braz, José Reinaldo Cerqueira - One of the best experts on this subject based on the ideXlab platform.
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Efectos del halotano, isoflurano y sevoflurano sobre la función renal en canes bajo pinzamiento aórtico infra-renal
Sociedade Brasileira de Anestesiologia, 2003Co-Authors: Bisinotto, Flora Margarida Barra, Braz, José Reinaldo CerqueiraAbstract:JUSTIFICATIVA E OBJETIVOS: O pinçamento infra-renal da aorta abdominal pode produzir alterações renais. O objetivo do estudo foi avaliar os efeitos do halotano, isoflurano e sevoflurano sobre a função renal, em cães submetidos a pinçamento aórtico infra-renal. MÉTODO: O estudo aleatório foi realizado em 30 cães, distribuídos em três grupos, de acordo com o anestésico halogenado utilizado durante a anestesia, em concentrações equipotentes de 0,75 CAM: GH (n = 10) - halotano a 0,67%; GI (n = 10) - isoflurano a 0,96%; e GS (n = 10) - sevoflurano a 1,8%. Em todos os animais foi realizada ligadura infra-renal da aorta, por período de 30 minutos. Os atributos renais foram estudados nos momentos: C (controle), após 15 (Ao15) e 30 (Ao30) minutos de pinçamento aórtico, e após 15 (DAo15) e 30 (DAo30) minutos do despinçamento aórtico. RESULTADOS: A depuração de água livre foi menor nos grupos GI e GS, em relação ao GH, após o despinçamento aórtico (p < 0,05). Durante o pinçamento aórtico, nos três grupos, houve aumento do débito urinário, da excreção urinária de sódio e da depuração de sódio, e diminuição da osmolaridade urinária (p < 0,05). A resistência vascular renal e a fração de filtração aumentaram somente em GS (p < 0,05), enquanto a excreção fracionária de sódio aumentou em GH e GI (p < 0,05). Após o despinçamento aórtico, houve normalização dos atributos que haviam se alterado, com exceção da osmolaridade urinária, que continuou em níveis menores do que os do controle em todos os grupos (p < 0,05). A resistência vascular renal e a fração de filtração continuaram mais elevadas em GS, acompanhadas por diminuição do fluxo sangüíneo renal e da depuração de para-aminohipurato de sódio (p < 0,05). CONCLUSÕES: No cão nas condições experimentais empregadas, a inalação de halotano e isoflurano a 0,75 CAM, mas não de sevoflurano, atenuou a principal alteração após o pinçamento infra-renal da aorta, que é o aumento da resistência vascular renal.BACKGROUND AND OBJECTIVES: Infra-renal aortic cross-clamping is associated to renal effects. This study aimed at analyzing halothane, Isoflurane and sevoflurane effects on renal function of dogs submitted to infra-renal aortic cross-clamping. METHODS: This study involved 30 mixed-breed dogs randomly distributed in three groups, according to equipotent anesthetic doses (0.75 MAC) of inhaled anesthetics: GH (n = 10) - 0.67% halothane; GI (n = 10) - 0.96% Isoflurane; and GS (n = 10) - 1.8% sevoflurane. All animals were submitted to infra-renal aortic cross-clamping for 30 minutes. Renal parameters were evaluated at control (C), 15 (Ao15) and (Ao30) minutes after aortic cross-clamping, and 15 (DAo15) and 30 (DAo30) minutes after aortic unclamping. RESULTS: Free water clearance was significantly lower in GI and GS as compared to GH (p < 0.05) after aortic unclamping. Urinary output, sodium urinary excretion and sodium clearance have significantly increased during aortic cross-clamping, while urinary osmolarity has decreased in all groups (p < 0.05). Renal vascular resistance and filtration fraction have increased during aortic cross-clamping in GS only, while sodium fractional excretion increased in GH and GI (p < 0.05). All renal parameters had returned to control levels after aortic unclamping, with the exception of urinary osmolality which has remained below control levels in all groups (p < 0.05). Renal vascular resistance and filtration fraction have remained higher in GS, followed by renal blood flow and PAH clearance decrease (p < 0.05). CONCLUSIONS: In dogs under our experimental conditions, 0.75 MAC of halothane or Isoflurane, but not 0.75 MAC of sevoflurane, have minimized renal vascular resistance increase, which is the major infra-renal aortic cross-clamping effect.JUSTIFICATIVA Y OBJETIVOS: El pinzamiento infra-renal de la aorta abdominal puede producir alteraciones renales. La finalidad del estudio fue evaluar los efectos del halotano, isoflurano y sevoflurano sobre la función renal, en canes sometidos a pinzamiento aórtico infra-renal. MÉTODO: El estudio aleatorio fue realizado en 30 canes, distribuidos en tres grupos, de acuerdo con el anestésico halogenado utilizado durante la anestesia, en concentraciones equipotentes de 0,75 CAM: GH (n = 10) - halotano a 0,67%; GI (n = 10) - isoflurano a 0,96%; y GS (n = 10) - sevoflurano a 1,8%. En todos los animales fue realizada ligadura infra-renal de la aorta, por un período de 30 minutos. Los atributos renales fueron estudiados en los momentos: C (control), después 15 (Ao15) y 30 (Ao30) minutos de pinzamiento aórtico, y después 15 (DAo15) y 30 (DAo30) minutos del despinzamiento aórtico. RESULTADOS: La depuración de agua libre fue menor en los grupos GI y GS, en relación a la GH, después del despinzamiento aórtico (p < 0,05). Durante el pinzamiento aórtico, en los tres grupos, hubo aumento del débito urinario, de la excreción urinaria de sodio y de la depuración de sodio, y diminución de la osmolaridad urinaria (p < 0,05). La resistencia vascular renal y la fracción de filtración aumentaron solamente en GS (p < 0,05), en cuanto la excreción fraccionaria de sodio aumentó en GH y GI (p < 0,05). Después del despinzamiento aórtico, hubo normalización de los atributos que se habían alterado, con excepción de la osmolaridad urinaria, que continuó en niveles menores que los del control en todos los grupos (p < 0,05). La resistencia vascular renal y la fracción de filtración continuaron más elevadas en GS, acompañadas por diminución del flujo sanguíneo renal y de la depuración de para-aminohipurato de sodio (p < 0,05). CONCLUSIONES: En el can, en las condiciones experimentales empleadas, la inhalación de halotano e isoflurano a 0,75 CAM, más no de sevoflurano, atenuó la principal alteración después del pinzamiento infra-renal de la aorta, que es un aumento de la resistencia vascular renal
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Efeitos do halotano, isoflurano e sevoflurano sobre a função renal em cães sob pinçamento aórtico infra-renal
Sociedade Brasileira de Anestesiologia, 2003Co-Authors: Bisinotto, Flora Margarida Barra, Braz, José Reinaldo CerqueiraAbstract:JUSTIFICATIVA E OBJETIVOS: O pinçamento infra-renal da aorta abdominal pode produzir alterações renais. O objetivo do estudo foi avaliar os efeitos do halotano, isoflurano e sevoflurano sobre a função renal, em cães submetidos a pinçamento aórtico infra-renal. MÉTODO: O estudo aleatório foi realizado em 30 cães, distribuídos em três grupos, de acordo com o anestésico halogenado utilizado durante a anestesia, em concentrações equipotentes de 0,75 CAM: GH (n = 10) - halotano a 0,67%; GI (n = 10) - isoflurano a 0,96%; e GS (n = 10) - sevoflurano a 1,8%. em todos os animais foi realizada ligadura infra-renal da aorta, por período de 30 minutos. Os atributos renais foram estudados nos momentos: C (controle), após 15 (Ao15) e 30 (Ao30) minutos de pinçamento aórtico, e após 15 (DAo15) e 30 (DAo30) minutos do despinçamento aórtico. RESULTADOS: A depuração de água livre foi menor nos grupos GI e GS, em relação ao GH, após o despinçamento aórtico (p < 0,05). Durante o pinçamento aórtico, nos três grupos, houve aumento do débito urinário, da excreção urinária de sódio e da depuração de sódio, e diminuição da osmolaridade urinária (p < 0,05). A resistência vascular renal e a fração de filtração aumentaram somente em GS (p < 0,05), enquanto a excreção fracionária de sódio aumentou em GH e GI (p < 0,05). Após o despinçamento aórtico, houve normalização dos atributos que haviam se alterado, com exceção da osmolaridade urinária, que continuou em níveis menores do que os do controle em todos os grupos (p < 0,05). A resistência vascular renal e a fração de filtração continuaram mais elevadas em GS, acompanhadas por diminuição do fluxo sangüíneo renal e da depuração de para-aminohipurato de sódio (p < 0,05). CONCLUSÕES: No cão nas condições experimentais empregadas, a inalação de halotano e isoflurano a 0,75 CAM, mas não de sevoflurano, atenuou a principal alteração após o pinçamento infra-renal da aorta, que é o aumento da resistência vascular renal.JUSTIFICATIVA Y OBJETIVOS: El pinzamiento infra-renal de la aorta abdominal puede producir alteraciones renales. La finalidad del estudio fue evaluar los efectos del halotano, isoflurano y sevoflurano sobre la función renal, en canes sometidos a pinzamiento aórtico infra-renal. MÉTODO: El estudio aleatorio fue realizado en 30 canes, distribuidos en tres grupos, de acuerdo con el anestésico halogenado utilizado durante la anestesia, en concentraciones equipotentes de 0,75 CAM: GH (n = 10) - halotano a 0,67%; GI (n = 10) - isoflurano a 0,96%; y GS (n = 10) - sevoflurano a 1,8%. En todos los animales fue realizada ligadura infra-renal de la aorta, por un período de 30 minutos. Los atributos renales fueron estudiados en los momentos: C (control), después 15 (Ao15) y 30 (Ao30) minutos de pinzamiento aórtico, y después 15 (DAo15) y 30 (DAo30) minutos del despinzamiento aórtico. RESULTADOS: La depuración de agua libre fue menor en los grupos GI y GS, en relación a la GH, después del despinzamiento aórtico (p < 0,05). Durante el pinzamiento aórtico, en los tres grupos, hubo aumento del débito urinario, de la excreción urinaria de sodio y de la depuración de sodio, y diminución de la osmolaridad urinaria (p < 0,05). La resistencia vascular renal y la fracción de filtración aumentaron solamente en GS (p < 0,05), en cuanto la excreción fraccionaria de sodio aumentó en GH y GI (p < 0,05). Después del despinzamiento aórtico, hubo normalización de los atributos que se habían alterado, con excepción de la osmolaridad urinaria, que continuó en niveles menores que los del control en todos los grupos (p < 0,05). La resistencia vascular renal y la fracción de filtración continuaron más elevadas en GS, acompañadas por diminución del flujo sanguíneo renal y de la depuración de para-aminohipurato de sodio (p < 0,05). CONCLUSIONES: En el can, en las condiciones experimentales empleadas, la inhalación de halotano e isoflurano a 0,75 CAM, más no de sevoflurano, atenuó la principal alteración después del pinzamiento infra-renal de la aorta, que es un aumento de la resistencia vascular renal.BACKGROUND and OBJECTIVES: Infra-renal aortic cross-clamping is associated to renal effects. This study aimed at analyzing halothane, Isoflurane and sevoflurane effects on renal function of dogs submitted to infra-renal aortic cross-clamping. METHODS: This study involved 30 mixed-breed dogs randomly distributed in three groups, according to equipotent anesthetic doses (0.75 MAC) of inhaled anesthetics: GH (n = 10) - 0.67% halothane; GI (n = 10) - 0.96% Isoflurane; and GS (n = 10) - 1.8% sevoflurane. All animals were submitted to infra-renal aortic cross-clamping for 30 minutes. Renal parameters were evaluated at control (C), 15 (Ao15) and (Ao30) minutes after aortic cross-clamping, and 15 (DAo15) and 30 (DAo30) minutes after aortic unclamping. RESULTS: Free water clearance was significantly lower in GI and GS as compared to GH (p < 0.05) after aortic unclamping. Urinary output, sodium urinary excretion and sodium clearance have significantly increased during aortic cross-clamping, while urinary osmolarity has decreased in all groups (p < 0.05). Renal vascular resistance and filtration fraction have increased during aortic cross-clamping in GS only, while sodium fractional excretion increased in GH and GI (p < 0.05). All renal parameters had returned to control levels after aortic unclamping, with the exception of urinary osmolality which has remained below control levels in all groups (p < 0.05). Renal vascular resistance and filtration fraction have remained higher in GS, followed by renal blood flow and PAH clearance decrease (p < 0.05). CONCLUSIONS: In dogs under our experimental conditions, 0.75 MAC of halothane or Isoflurane, but not 0.75 MAC of sevoflurane, have minimized renal vascular resistance increase, which is the major infra-renal aortic cross-clamping effect
Mihwa Kim - One of the best experts on this subject based on the ideXlab platform.
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The Volatile Anesthetic Isoflurane Increases Endothelial Adenosine Generation via Microparticle Ecto-59- Nucleotidase (CD73) Release
2016Co-Authors: Mihwa Kim, Ahrom Ham, Kevin M Brown, Katelyn Yu-mi Kim, Thomas H LeeAbstract:Endothelial dysfunction is common in acute and chronic organ injury. Isoflurane is a widely used halogenated volatile anesthetic during the perioperative period and protects against endothelial cell death and inflammation. In this study, we tested whether Isoflurane induces endothelial ecto-59-nucleotidase (CD73) and cytoprotective adenosine generation to protect against endothelial cell injury. Clinically relevant concentrations of Isoflurane induced CD73 activity and increased adenosine generation in cultured human umbilical vein or mouse glomerular endothelial cells. Surprisingly, Isoflurane-mediated induction of endothelial CD73 activity occurred within 1 hr and without synthesizing new CD73. We determined that Isoflurane rapidly increased CD73 containing endothelial microparticles into the cell culture media. Indeed, microparticles isolated from Isoflurane-treated endothelial cells had significantly higher CD73 activity as well as increased CD73 protein. In vivo, plasma from mice anesthetized with Isoflurane had significantly higher endothelial cell-derived CD144+ CD73+ microparticles and had increased microparticle CD73 activity compared to plasma from pentobarbital-anesthetized mice. Supporting a critical role of CD73 in Isoflurane-mediated endothelial protection, a selective CD73 inhibitor (APCP) prevented Isoflurane-induced protection against human endothelial cell inflammation and apoptosis. In addition, Isoflurane activated endothelial cells Rho kinase evidenced by myosin phosphatase target subunit-1 and myosin light chain phosphorylation. Furthermore, Isoflurane-induced release of CD73 containing microparticles was significantl
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the volatile anesthetic Isoflurane increases endothelial adenosine generation via microparticle ecto 5 nucleotidase cd73 release
PLOS ONE, 2014Co-Authors: Mihwa Kim, Ahrom Ham, Kevin M Brown, Katelyn Yu-mi Kim, Thomas H LeeAbstract:Endothelial dysfunction is common in acute and chronic organ injury. Isoflurane is a widely used halogenated volatile anesthetic during the perioperative period and protects against endothelial cell death and inflammation. In this study, we tested whether Isoflurane induces endothelial ecto-5′-nucleotidase (CD73) and cytoprotective adenosine generation to protect against endothelial cell injury. Clinically relevant concentrations of Isoflurane induced CD73 activity and increased adenosine generation in cultured human umbilical vein or mouse glomerular endothelial cells. Surprisingly, Isoflurane-mediated induction of endothelial CD73 activity occurred within 1 hr and without synthesizing new CD73. We determined that Isoflurane rapidly increased CD73 containing endothelial microparticles into the cell culture media. Indeed, microparticles isolated from Isoflurane-treated endothelial cells had significantly higher CD73 activity as well as increased CD73 protein. In vivo, plasma from mice anesthetized with Isoflurane had significantly higher endothelial cell-derived CD144+ CD73+ microparticles and had increased microparticle CD73 activity compared to plasma from pentobarbital-anesthetized mice. Supporting a critical role of CD73 in Isoflurane-mediated endothelial protection, a selective CD73 inhibitor (APCP) prevented Isoflurane-induced protection against human endothelial cell inflammation and apoptosis. In addition, Isoflurane activated endothelial cells Rho kinase evidenced by myosin phosphatase target subunit-1 and myosin light chain phosphorylation. Furthermore, Isoflurane-induced release of CD73 containing microparticles was significantly attenuated by a selective Rho kinase inhibitor (Y27632). Taken together, we conclude that the volatile anesthetic Isoflurane causes Rho kinase-mediated release of endothelial microparticles containing preformed CD73 and increase adenosine generation to protect against endothelial apoptosis and inflammation.
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the volatile anesthetic Isoflurane induces ecto 5 nucleotidase cd73 to protect against renal ischemia and reperfusion injury
Kidney International, 2013Co-Authors: Mihwa Kim, Vivette D Dagati, Ahrom Ham, Joo Yun Kim, Kevin M Brown, Thomas H LeeAbstract:The volatile anesthetic Isoflurane protects against renal ischemia and reperfusion injury by releasing renal tubular TGF-β1. As adenosine is a powerful cytoprotective molecule, we tested whether TGF-β1 generated by Isoflurane induces renal tubular ecto-5′-nucleotidase (CD73) and adenosine to protect against renal ischemia and reperfusion injury. Isoflurane induced new CD73 synthesis and increased adenosine generation in cultured kidney proximal tubule cells and in mouse kidney. Moreover, a TGF-β1-neutralizing antibody prevented Isoflurane-mediated induction of CD73 activity. Mice anesthetized with Isoflurane after renal ischemia and reperfusion had significantly reduced plasma creatinine and decreased renal tubular necrosis, neutrophil infiltration, and apoptosis compared with pentobarbital-anesthetized mice. Isoflurane failed to protect against renal ischemia and reperfusion injury in CD73-deficient mice, in mice pretreated with a selective CD73 inhibitor, or in mice treated with an adenosine receptor antagonist. The TGF-β1-neutralizing antibody or the CD73 inhibitor attenuated Isoflurane-mediated protection against HK-2 cell apoptosis. Thus, Isoflurane causes TGF-β1-dependent induction of renal tubular CD73 and adenosine generation to protect against renal ischemia and reperfusion injury. Modulation of this pathway may have important therapeutic implications to reduce morbidity and mortality arising from ischemic acute kidney injury.
Kevin M Brown - One of the best experts on this subject based on the ideXlab platform.
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The Volatile Anesthetic Isoflurane Increases Endothelial Adenosine Generation via Microparticle Ecto-59- Nucleotidase (CD73) Release
2016Co-Authors: Mihwa Kim, Ahrom Ham, Kevin M Brown, Katelyn Yu-mi Kim, Thomas H LeeAbstract:Endothelial dysfunction is common in acute and chronic organ injury. Isoflurane is a widely used halogenated volatile anesthetic during the perioperative period and protects against endothelial cell death and inflammation. In this study, we tested whether Isoflurane induces endothelial ecto-59-nucleotidase (CD73) and cytoprotective adenosine generation to protect against endothelial cell injury. Clinically relevant concentrations of Isoflurane induced CD73 activity and increased adenosine generation in cultured human umbilical vein or mouse glomerular endothelial cells. Surprisingly, Isoflurane-mediated induction of endothelial CD73 activity occurred within 1 hr and without synthesizing new CD73. We determined that Isoflurane rapidly increased CD73 containing endothelial microparticles into the cell culture media. Indeed, microparticles isolated from Isoflurane-treated endothelial cells had significantly higher CD73 activity as well as increased CD73 protein. In vivo, plasma from mice anesthetized with Isoflurane had significantly higher endothelial cell-derived CD144+ CD73+ microparticles and had increased microparticle CD73 activity compared to plasma from pentobarbital-anesthetized mice. Supporting a critical role of CD73 in Isoflurane-mediated endothelial protection, a selective CD73 inhibitor (APCP) prevented Isoflurane-induced protection against human endothelial cell inflammation and apoptosis. In addition, Isoflurane activated endothelial cells Rho kinase evidenced by myosin phosphatase target subunit-1 and myosin light chain phosphorylation. Furthermore, Isoflurane-induced release of CD73 containing microparticles was significantl
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the volatile anesthetic Isoflurane increases endothelial adenosine generation via microparticle ecto 5 nucleotidase cd73 release
PLOS ONE, 2014Co-Authors: Mihwa Kim, Ahrom Ham, Kevin M Brown, Katelyn Yu-mi Kim, Thomas H LeeAbstract:Endothelial dysfunction is common in acute and chronic organ injury. Isoflurane is a widely used halogenated volatile anesthetic during the perioperative period and protects against endothelial cell death and inflammation. In this study, we tested whether Isoflurane induces endothelial ecto-5′-nucleotidase (CD73) and cytoprotective adenosine generation to protect against endothelial cell injury. Clinically relevant concentrations of Isoflurane induced CD73 activity and increased adenosine generation in cultured human umbilical vein or mouse glomerular endothelial cells. Surprisingly, Isoflurane-mediated induction of endothelial CD73 activity occurred within 1 hr and without synthesizing new CD73. We determined that Isoflurane rapidly increased CD73 containing endothelial microparticles into the cell culture media. Indeed, microparticles isolated from Isoflurane-treated endothelial cells had significantly higher CD73 activity as well as increased CD73 protein. In vivo, plasma from mice anesthetized with Isoflurane had significantly higher endothelial cell-derived CD144+ CD73+ microparticles and had increased microparticle CD73 activity compared to plasma from pentobarbital-anesthetized mice. Supporting a critical role of CD73 in Isoflurane-mediated endothelial protection, a selective CD73 inhibitor (APCP) prevented Isoflurane-induced protection against human endothelial cell inflammation and apoptosis. In addition, Isoflurane activated endothelial cells Rho kinase evidenced by myosin phosphatase target subunit-1 and myosin light chain phosphorylation. Furthermore, Isoflurane-induced release of CD73 containing microparticles was significantly attenuated by a selective Rho kinase inhibitor (Y27632). Taken together, we conclude that the volatile anesthetic Isoflurane causes Rho kinase-mediated release of endothelial microparticles containing preformed CD73 and increase adenosine generation to protect against endothelial apoptosis and inflammation.
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the volatile anesthetic Isoflurane induces ecto 5 nucleotidase cd73 to protect against renal ischemia and reperfusion injury
Kidney International, 2013Co-Authors: Mihwa Kim, Vivette D Dagati, Ahrom Ham, Joo Yun Kim, Kevin M Brown, Thomas H LeeAbstract:The volatile anesthetic Isoflurane protects against renal ischemia and reperfusion injury by releasing renal tubular TGF-β1. As adenosine is a powerful cytoprotective molecule, we tested whether TGF-β1 generated by Isoflurane induces renal tubular ecto-5′-nucleotidase (CD73) and adenosine to protect against renal ischemia and reperfusion injury. Isoflurane induced new CD73 synthesis and increased adenosine generation in cultured kidney proximal tubule cells and in mouse kidney. Moreover, a TGF-β1-neutralizing antibody prevented Isoflurane-mediated induction of CD73 activity. Mice anesthetized with Isoflurane after renal ischemia and reperfusion had significantly reduced plasma creatinine and decreased renal tubular necrosis, neutrophil infiltration, and apoptosis compared with pentobarbital-anesthetized mice. Isoflurane failed to protect against renal ischemia and reperfusion injury in CD73-deficient mice, in mice pretreated with a selective CD73 inhibitor, or in mice treated with an adenosine receptor antagonist. The TGF-β1-neutralizing antibody or the CD73 inhibitor attenuated Isoflurane-mediated protection against HK-2 cell apoptosis. Thus, Isoflurane causes TGF-β1-dependent induction of renal tubular CD73 and adenosine generation to protect against renal ischemia and reperfusion injury. Modulation of this pathway may have important therapeutic implications to reduce morbidity and mortality arising from ischemic acute kidney injury.
Ahrom Ham - One of the best experts on this subject based on the ideXlab platform.
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The Volatile Anesthetic Isoflurane Increases Endothelial Adenosine Generation via Microparticle Ecto-59- Nucleotidase (CD73) Release
2016Co-Authors: Mihwa Kim, Ahrom Ham, Kevin M Brown, Katelyn Yu-mi Kim, Thomas H LeeAbstract:Endothelial dysfunction is common in acute and chronic organ injury. Isoflurane is a widely used halogenated volatile anesthetic during the perioperative period and protects against endothelial cell death and inflammation. In this study, we tested whether Isoflurane induces endothelial ecto-59-nucleotidase (CD73) and cytoprotective adenosine generation to protect against endothelial cell injury. Clinically relevant concentrations of Isoflurane induced CD73 activity and increased adenosine generation in cultured human umbilical vein or mouse glomerular endothelial cells. Surprisingly, Isoflurane-mediated induction of endothelial CD73 activity occurred within 1 hr and without synthesizing new CD73. We determined that Isoflurane rapidly increased CD73 containing endothelial microparticles into the cell culture media. Indeed, microparticles isolated from Isoflurane-treated endothelial cells had significantly higher CD73 activity as well as increased CD73 protein. In vivo, plasma from mice anesthetized with Isoflurane had significantly higher endothelial cell-derived CD144+ CD73+ microparticles and had increased microparticle CD73 activity compared to plasma from pentobarbital-anesthetized mice. Supporting a critical role of CD73 in Isoflurane-mediated endothelial protection, a selective CD73 inhibitor (APCP) prevented Isoflurane-induced protection against human endothelial cell inflammation and apoptosis. In addition, Isoflurane activated endothelial cells Rho kinase evidenced by myosin phosphatase target subunit-1 and myosin light chain phosphorylation. Furthermore, Isoflurane-induced release of CD73 containing microparticles was significantl
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the volatile anesthetic Isoflurane increases endothelial adenosine generation via microparticle ecto 5 nucleotidase cd73 release
PLOS ONE, 2014Co-Authors: Mihwa Kim, Ahrom Ham, Kevin M Brown, Katelyn Yu-mi Kim, Thomas H LeeAbstract:Endothelial dysfunction is common in acute and chronic organ injury. Isoflurane is a widely used halogenated volatile anesthetic during the perioperative period and protects against endothelial cell death and inflammation. In this study, we tested whether Isoflurane induces endothelial ecto-5′-nucleotidase (CD73) and cytoprotective adenosine generation to protect against endothelial cell injury. Clinically relevant concentrations of Isoflurane induced CD73 activity and increased adenosine generation in cultured human umbilical vein or mouse glomerular endothelial cells. Surprisingly, Isoflurane-mediated induction of endothelial CD73 activity occurred within 1 hr and without synthesizing new CD73. We determined that Isoflurane rapidly increased CD73 containing endothelial microparticles into the cell culture media. Indeed, microparticles isolated from Isoflurane-treated endothelial cells had significantly higher CD73 activity as well as increased CD73 protein. In vivo, plasma from mice anesthetized with Isoflurane had significantly higher endothelial cell-derived CD144+ CD73+ microparticles and had increased microparticle CD73 activity compared to plasma from pentobarbital-anesthetized mice. Supporting a critical role of CD73 in Isoflurane-mediated endothelial protection, a selective CD73 inhibitor (APCP) prevented Isoflurane-induced protection against human endothelial cell inflammation and apoptosis. In addition, Isoflurane activated endothelial cells Rho kinase evidenced by myosin phosphatase target subunit-1 and myosin light chain phosphorylation. Furthermore, Isoflurane-induced release of CD73 containing microparticles was significantly attenuated by a selective Rho kinase inhibitor (Y27632). Taken together, we conclude that the volatile anesthetic Isoflurane causes Rho kinase-mediated release of endothelial microparticles containing preformed CD73 and increase adenosine generation to protect against endothelial apoptosis and inflammation.
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the volatile anesthetic Isoflurane induces ecto 5 nucleotidase cd73 to protect against renal ischemia and reperfusion injury
Kidney International, 2013Co-Authors: Mihwa Kim, Vivette D Dagati, Ahrom Ham, Joo Yun Kim, Kevin M Brown, Thomas H LeeAbstract:The volatile anesthetic Isoflurane protects against renal ischemia and reperfusion injury by releasing renal tubular TGF-β1. As adenosine is a powerful cytoprotective molecule, we tested whether TGF-β1 generated by Isoflurane induces renal tubular ecto-5′-nucleotidase (CD73) and adenosine to protect against renal ischemia and reperfusion injury. Isoflurane induced new CD73 synthesis and increased adenosine generation in cultured kidney proximal tubule cells and in mouse kidney. Moreover, a TGF-β1-neutralizing antibody prevented Isoflurane-mediated induction of CD73 activity. Mice anesthetized with Isoflurane after renal ischemia and reperfusion had significantly reduced plasma creatinine and decreased renal tubular necrosis, neutrophil infiltration, and apoptosis compared with pentobarbital-anesthetized mice. Isoflurane failed to protect against renal ischemia and reperfusion injury in CD73-deficient mice, in mice pretreated with a selective CD73 inhibitor, or in mice treated with an adenosine receptor antagonist. The TGF-β1-neutralizing antibody or the CD73 inhibitor attenuated Isoflurane-mediated protection against HK-2 cell apoptosis. Thus, Isoflurane causes TGF-β1-dependent induction of renal tubular CD73 and adenosine generation to protect against renal ischemia and reperfusion injury. Modulation of this pathway may have important therapeutic implications to reduce morbidity and mortality arising from ischemic acute kidney injury.
