Navegando por Palavras-chave "heme oxygenase 1"
Agora exibindo 1 - 4 de 4
Resultados por página
Opções de Ordenação
- ItemAcesso aberto (Open Access)The blockade of cyclooxygenases-1 and-2 reduces the effects of hypoxia on endothelial cells(Assoc Bras Divulg Cientifica, 2006-09-01) Gloria, Maria Aparecida da [UNIFESP]; Cenedeze, Marcos Antonio [UNIFESP]; Pacheco-Silva, Alvaro [UNIFESP]; Camara, Niels Olsen Saraiva [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Universidade de São Paulo (USP)Hypoxia activates endothelial cells by the action of reactive oxygen species generated in part by cyclooxygenases (COX) production enhancing leukocyte transmigration. We investigated the effect of specific COX inhibition on the function of endothelial cells exposed to hypoxia. Mouse immortalized endothelial cells were subjected to 30 min of oxygen deprivation by gas exchange. Acridine orange/ ethidium bromide dyes and lactate dehydrogenase activity were used to monitor cell viability. the mRNA of COX-1 and -2 was amplified and semi-quantified before and after hypoxia in cells treated or not with indomethacin, a non-selective COX inhibitor. Expression of RANTES ( regulated upon activation, normal T cell expressed and secreted) protein and the protective role of heme oxygenase-1 (HO-1) were also investigated by PCR. Gas exchange decreased partial oxygen pressure (PaO2) by 45.12 +/- 5.85% (from 162 +/- 10 to 73 +/- 7.4 mmIIg). Thirty minutes of hypoxia decreased cell viability and enhanced lactate dehydrogenase levels compared to control (73.1 +/- 2.7 vs 91.2 +/- 0.9%, P < 0.02; 35.96 +/- 11.64 vs 22.19 +/- 9.65%, P = 0.002, respectively). COX-2 and HO-1 mRNA were up-regulated after hypoxia. Indomethacin (300 mu M) decreased COX-2, HO-1, hypoxiainducible factor-1 alpha and RANTES mRNA and increased cell viability after hypoxia. We conclude that blockade of COX up-regulation can ameliorate endothelial injury, resulting in reduced production of chemokines.
- ItemSomente MetadadadosHeme oxygenase 1 and renal ischemia and reperfusion injury: the impact of immunosuppressive drug(Elsevier B.V., 2006-12-20) Goncalves, Giselle Martins; Cenedeze, Marcos Antonio; Feitoza, Carla Quarim; Paula, Carolina Batista de; Macusso, Georgia Daniela; Pinheiro, Helady Sanders; Antunes Teixeira, Vicente de Paula; Reis, Marlene Antonia dos; Pacheco-Silva, Alvaro; Camara, Niels Olsen Saraiva; Universidade de São Paulo (USP); Univ Fed Uberaba; Universidade Federal de São Paulo (UNIFESP)Background: Ischemia and reperfusion injury (IRI) is the main etiology of acute renal failure in native and transplanted kidneys. in the transplantation field, immunosuppressive drugs may play an additional role in acute graft dysfunction. Acute cyclosporine nephrotoxicity (ATN) can result from vasoconstriction of the afferent arterioles, which may exacerbate deceased renal transplantation. HO-1 is a protective gene with anti-inflammatory and anti-apoptotic actions. We investigated whether HO-1 played a role in cyclosporine-induced renal dysfunction in an established model of IRLMethods: Cyclosporine (100 mg/kg) was administered to mice before being subjected to 45 min of ischemia. Blood and kidney samples were collected at 24, 48 and 120 h after surgery. Acute tubular necrosis and tubular regeneration were quantified. HO-1 gene transcripts were amplified by real-time PCR.Results: Animals subjected to IRI presented with impaired renal function that peaked at 24 h (2.05 +/- 0.23 mg/dL), decreasing thereafter. Treatment with cyclosporine caused even more renal dysfunction at 48 h, sustained up to 120 h after reperfusion (1.53 +/- 0.6 mg/dL), when compared to the controls (0.63 +/- 0.09 mg/dL, p < 0,05). Cyclosporine delayed tubular regeneration that was normally higher in controls at day 5 (67.0% vs. 37.6%, p < 0.05). HO-1 was markedly up-regulated after IRI, and its expression was decreased by cyclosporine (2.06 folds). However, prior induction of HO-1 by cobalt protoporphyrin improved renal dysfunction.Conclusions: These results demonstrated that cyclosporine used in ischemic injured organs might also negatively affect post-transplantation recovery. (c) 2006 Elsevier B.V. All rights reserved.
- ItemSomente MetadadadosInfluence of TH1/TH2 switched immune response on renal ischemia-reperfusion injury(Karger, 2006-01-01) Marques, Vilmar Paiva [UNIFESP]; Gonçalves, Giselle Martins [UNIFESP]; Feitoza, Carla Quarin [UNIFESP]; Cenedeze, Marcos Antonio [UNIFESP]; Bertocchi, Ana Paula Fernandes [UNIFESP]; Damiao, Marcio Jose [UNIFESP]; Pinheiro, Helady Sanders; Teixeira, Vicente Paula Antunes; Reis, Marlene Antonia dos; Pacheco-Silva, Alvaro [UNIFESP]; Camara, Niels Olsen Saraiva [UNIFESP]; Universidade de São Paulo (USP); Universidade Federal de São Paulo (UNIFESP)Background/Aims: Recent evidence shows a critical role of the CD4+ T cell with the Th1/Th2 paradigm as a possible effector mechanism in ischemia and reperfusion injury. We hypothesize that a polarized Th1 activation response may negatively influence the renal IRI through its relationship with chemokine production (MCP-1) and with a protective tissue response (HO-1). Methods: We subjected mice to renal ischemia for 45 min using IL-4 and IL-12 knockout C57BL/6. We then measured serum urea levels, performed histomorphometric analysis for tubular necrosis and regeneration, and evaluated the mRNA expression of HO-1, t-bet, Gata-3 and MCP-1 by real-time PCR at 24,48 and 120 h after surgery. Results/Conclusions: the IL-4 knockout mice had a statistically significant rise in serum urea levels post IRI compared with control animals. the IL-12-deficient mice were not affected. the IL-4-deficient mice had a statistically significant increase in tubular injury and impairment in cell regeneration. the IRI in IL-4-deficient mice was accompanied by higher levels of HO-1, t-bet and later up-regulation of MCP-1. These findings suggest that the deleterious effects of the Th1 cell involve increased production of chemokines such as MCP-1. Copyright (c) 2006 S. Karger AG, Basel.
- ItemSomente MetadadadosThe role of heme oxygenase 1 in rapamycin-induced renal dysfunction after ischemia and reperfusion injury(Nature Publishing Group, 2006-11-01) Goncalves, G. M.; Cenedeze, Marcos Antonio [UNIFESP]; Feitoza, C. Q.; Wang, P. M. H.; Bertocchi, A. P. F.; Damiao, M. J.; Pinheiro, H. S.; Teixeira, V. P. Antunes; Reis, M. A. dos; Pacheco-Silva, A.; Camara, N. O. S.; Universidade Federal de São Paulo (UNIFESP); Univ Fed Triangulo Mineiro; Universidade de São Paulo (USP)Ischemia and reperfusion injury ( IRI) is the main etiology of acute renal failure in native and transplanted kidneys. in the transplantation field, immunosuppressive drugs may play an additional role in acute graft dysfunction. Rapamycin may impair renal regeneration post IRI. Heme oxygenase 1 ( HO-1) is a protective gene with anti-inflammatory and anti-apoptotic actions. We investigated whether HO-1 played a role in rapamycin-induced renal dysfunction in an established model of IRI. Rapamycin ( 3mg/kg) was administered to mice before being subjected to 45 min of ischemia. Animals subjected to IRI presented with impaired renal function that peaked at 24h ( 2.05 +/- 0.23mg/dl), decreasing thereafter. Treatment with rapamycin caused even more renal dysfunctions ( 2.30 +/- 0.33mg/dl), sustained up to 120 h after reperfusion ( 1.54 +/- 0.4mg/dl), when compared to the control ( 0.63 +/- 0.09mg/dl, P < 0.05). Rapamycin delayed tubular regeneration that was normally higher in the control group at day 5 ( 68.53 +/- 2.30 vs 43.63 +/- 3.11%, P < 0.05). HO-1 was markedly upregulated after IRI and its expression was even enhanced by rapamycin ( 1.32-fold). However, prior induction of HO-1 by cobalt protoporphyrin improved the renal dysfunction imposed by rapamycin, mostly at later time points. These results demonstrated that rapamycin used in ischemic-injured organs could also negatively affect post-transplantation recovery. Modulation of HO-1 expression may represent a feasible approach to limit rapamycin acute toxicity.