RESUMO
Endoplasmic reticulum stress (ERS) can initiate inflammation, and the coupling of these responses is thought to be fundamental to the pathogenesis of cardiovascular disease. However, the mechanism linking ERS and inflammation in myocardial ischemia/reperfusion needs further investigation. Cultured cardiomyocytes were pretreated with SP600125 or salubrinal, followed by tunicamycin to clarify the involvement of the IRE1α and PERK pathways in ERS inflammation. The cardiomyocytes were given hypoxia/reoxygenation (H/R), and the effects of the NF-κB inhibitor, SN50, were followed. GRP78 protein levels were similar in the tunicamycin (Tm), salubrinal, and SP600125 groups, but were lower in cells treated with SN50. SN50 might effectively block the H/R-induced link between ERS and inflammation in cardiomyocytes by decreasing GRP78. This knowledge will aid in the development of therapies for myocardial ischemia/reperfusion injury.
Assuntos
Hipóxia Celular , Estresse do Retículo Endoplasmático/fisiologia , Inflamação , Miócitos Cardíacos/metabolismo , NF-kappa B/metabolismo , Animais , Antracenos/farmacologia , Células Cultivadas , Cinamatos/farmacologia , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Endorribonucleases/metabolismo , Frequência Cardíaca/efeitos dos fármacos , Proteínas de Choque Térmico/metabolismo , Complexos Multienzimáticos/metabolismo , Miócitos Cardíacos/citologia , Miócitos Cardíacos/efeitos dos fármacos , Peptídeos/farmacologia , Proteínas Serina-Treonina Quinases/metabolismo , Ratos , Ratos Sprague-Dawley , Tioureia/análogos & derivados , Tioureia/farmacologia , Fator de Necrose Tumoral alfa/metabolismo , Tunicamicina/farmacologia , eIF-2 Quinase/metabolismoRESUMO
Pheochromocytoma is a tumor derived from chromaffin tissue in the adrenergic system with excessive secretion of catecholamine.Pheochromocytoma occurs at any age of patients,commonly in 40-60 years,and the incidence is slightly higher in women than in men.In recent years,studies have shown that the mutations of von Hippel-Lindau gene (VHL),rearranged during transfection gene (RET),neurofibromatosis type 1 gene (NF-1),succinate dehydrogenase gene (SDH),transmembrane protein 127 gene (TMEM127),myelocytomatosis oncogene-associated factor X gene (MAX) are associated with pheochromocytoma.Immunohistochemical studies have revealed that a number of molecular markers,such as telomerase,vascular endothelial growth factor,cyclooxygenase-2,adrenomedullin,plasma chromaffin protein A,signal transducer and activator of transcription-3 are of value in identification of tumor origin,its biological behaviors and differentiation of pheochromocytoma. This article reviews the newest research progresses in molecular biology of pheochromocytoma.