Cytoprotective role of heme oxygenase-1 and heme degradation derived end products in liver injury

Autor(es)

Taemi Origassa, Clarice Silvia ; Saraiva Camara, Niels Olsen

• Tipo de documento: Artigo Científico
• Fonte: WORLD JOURNAL OF HEPATOLOGY; v. 5, n. 10, p. 9-pg., 2013-10-27.

Resumo

The activation of heme oxygenase-1 (HO-1) appears to be an endogenous defensive mechanism used by cells to reduce inflammation and tissue damage in a number of injury models. HO-1, a stress-responsive enzyme that catabolizesheme into carbon monoxide (CO), biliverdin and iron, has previously been shown to protect grafts from ischemia/reperfusion and rejection. In addition, the products of the HO-catalyzed reaction, particularly CO and biliverdin/bilirubin, have been shown to exert protective effects in the liver against a number of stimuli, as in chronic hepatitis C and in transplanted liver grafts. Furthermore, the induction of HO-1 expression can protect the liver against damage caused by a number of chemical compounds. More specifically, the CO derived from HO-1-mediated heme catabolism has been shown to be involved in the regulation of inflammation; furthermore, administration of low concentrations of exogenous CO has a protective effect against inflammation. Both murine and human HO-1 deficiencies have systemic manifestations associated with iron metabolism, such as hepatic overload (with signs of a chronic hepatitis) and iron deficiency anemia (with paradoxical increased levels of ferritin). Hypoxia induces HO-1 expression in multiple rodent, bovine and monkey cell lines, but interestingly, hypoxia represses expression of the human HO-1 gene in a variety of human cell types (endothelial cells, epithelial cells, T cells). These data suggest that HO-1 and CO are promising novel therapeutic molecules for patients with inflammatory diseases. In this review, we present what is currently known regarding the role of HO-1 in liver injuries and in particular, we focus on the implications of targeted induction of HO-1 as a potential therapeutic strategy to protect the liver against chemically induced injury. (C) 2013 Baishideng. All rights reserved. (AU)

• Processo FAPESP: 07/07139-3 - Investigando o papel da heme-oxigenase 1 em diferentes processos inflamatórios renais em modelos animais
• Beneficiário: Niels Olsen Saraiva Câmara
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 10/02024-6 - Modulação da transição endotélio mesenquimal pela heme oxigenase 1: relevância para o estudo da progressão da doença renal.
• Beneficiário: Clarice Silvia Taemi Origassa
• Modalidade de apoio: Bolsas no Brasil - Doutorado