RESUMO
OBJECTIVE: To measure the release of plasma nuclear deoxyribonucleic acid (DNA) and to assess the relationship between nuclear DNA level and acute kidney injury occurrence in patients undergoing cardiac surgery. SETTING: Cardiovascular anesthesiology and intensive care unit of a large tertiary-care university hospital. DESIGN: Prospective observational study. PARTICIPANTS: Fifty adult patients undergoing cardiac surgery. INTERVENTIONS: Nuclear DNA concentration was measured in the plasma. The relationship between the level of nuclear DNA and the incidence of acute kidney injury after coronary artery bypass grafting was investigated. MEASUREMENTS AND MAIN RESULTS: Cardiac surgery leads to significant increase in plasma nuclear DNA with peak levels 12 hours after surgery (median [interquartile range] 7.0 [9.6-22.5] µg/mL). No difference was observed between off-pump and on-pump surgical techniques. Nuclear DNA was the only predictor of acute kidney injury between baseline and early postoperative risk factors. CONCLUSIONS: The authors found an increase of nuclear DNA in the plasma of patients who had undergone coronary artery bypass grafting, with a peak after 12 hours and an association of nuclear DNA with postoperative acute kidney injury.
Assuntos
Injúria Renal Aguda/sangue , Injúria Renal Aguda/diagnóstico , Ponte de Artéria Coronária/efeitos adversos , DNA/sangue , Complicações Pós-Operatórias/sangue , Complicações Pós-Operatórias/diagnóstico , Injúria Renal Aguda/etiologia , Idoso , Ponte de Artéria Coronária/tendências , Humanos , Pessoa de Meia-Idade , Projetos Piloto , Complicações Pós-Operatórias/etiologia , Valor Preditivo dos Testes , Estudos Prospectivos , Fatores de RiscoRESUMO
Interphase microtubules are organized into a radial array with centrosome in the center. This organization is a subject of cellular regulation that can be driven by protein phosphorylation. Only few protein kinases that regulate microtubule array in interphase cells have been described. Ste20-like protein kinase LOSK (SLK) was identified as a microtubule and centrosome-associated protein. In this study we have shown that the inhibition of LOSK activity by dominant-negative mutant K63R-DeltaT or by LOSK depletion with RNAi leads to unfocused microtubule arrangement. Microtubule disorganization is prominent in Vero, CV-1, and CHO-K1 cells but less distinct in HeLa cells. The effect is a result neither of microtubule stabilization nor of centrosome disruption. In cells with suppressed LOSK activity centrosomes are unable to anchor or to cap microtubules, though they keep nucleating microtubules. These centrosomes are depleted of dynactin. Vero cells overexpressing K63R-DeltaT have normal dynactin "comets" at microtubule ends and unaltered morphology of Golgi complex but are unable to polarize it at the wound edge. We conclude that protein kinase LOSK is required for radial microtubule organization and for the proper localization of Golgi complex in various cell types.