tailieunhanh - báo cáo hóa học:" Liver mitochondrial dysfunction is reverted by insulin-like growth factor II (IGF-II) in aging rats"

Tuyển tập các báo cáo nghiên cứu về hóa học được đăng trên tạp chí sinh học đề tài : Liver mitochondrial dysfunction is reverted by insulin-like growth factor II (IGF-II) in aging rats | Garcia-Fernandez et al. Journal of Translational Medicine 2011 9 123 http content 9 1 123 JOURNAL OF TRANSLATIONAL MEDICINE RESEARCH Open Access Liver mitochondrial dysfunction is reverted by insulin-like growth factor II IGF-II in aging rats Maria Garcia-Fernandez1 Inma Sierra2 Juan E Puche2 Lucia Guerra2 and Inma Castilla-Cortazar2 Abstract Background Serum IGF-I and IGF-II levels decline with age. IGF-I replacement therapy reduces the impact of age in rats. We have recently reported that IGF-II is able to act in part as an analogous of IGF-I in aging rats reducing oxidative damage in brain and liver associated with a normalization of antioxidant enzyme activities. Since mitochondria seem to be the most important cellular target of IGF-I the aim of this work was to investigate whether the cytoprotective actions of IGF-II therapy are mediated by mitochondrial protection. Methods Three groups of rats were included in the experimental protocol young controls 17 weeks old untreated old rats 103 weeks old and aging rats 103 weeks old treated with IGF-II 2 pg 100 g body weight and day for 30 days. Results Compared with young controls untreated old rats showed an increase of oxidative damage in isolated mitochondria with a dysfunction characterized by reduction of mitochondrial membrane potential MMP and ATP synthesis and increase of intramitochondrial free radicals production and proton leak rates. In addition in untreated old rats mitochondrial respiration was not blocked by atractyloside. In accordance old rats showed an overexpression of the active fragment of caspases 3 and 9 in liver homogenates. IGF-II therapy corrected all of these parameters of mitochondrial dysfunction and reduced activation of caspases. Conclusions The cytoprotective effects of IGF-II are related to mitochondrial protection leading to increased ATP production reducing free radical generation oxidative damage and apoptosis. Background The reduced activity of the