Erythropoietin Modulates Autophagy Signaling in the Developing Rat Brain in an In Vivo Model of Oxygen-Toxicity

被引:39
作者
Bendix, Ivo [1 ]
Schulze, Corina [2 ]
von Haefen, Clarissa [2 ]
Gellhaus, Alexandra [3 ]
Endesfelder, Stefanie [4 ]
Heumann, Rolf [5 ]
Felderhoff-Mueser, Ursula [1 ]
Sifringer, Marco [2 ]
机构
[1] Univ Hosp Essen, Dept Pediat 1, D-45122 Essen, Germany
[2] Charite, Dept Anaesthesiol & Intens Care Med, Campus Virchow Klinikum, D-13353 Berlin, Germany
[3] Univ Duisburg Essen, Inst Mol Biol, D-45122 Essen, Germany
[4] Charite, Dept Neonatol, Campus Virchow Klinikum, D-13353 Berlin, Germany
[5] Ruhr Univ Bochum, Dept Mol Neurobiochem, D-44780 Bochum, Germany
关键词
autophagy; developing brain; oxidative stress; hyperoxia; erythropoietin; INDUCED CELL-DEATH; OXIDATIVE STRESS; BECLIN-1; EXPRESSION; DISEASE; SYSTEM; NEURODEGENERATION; MITOCHONDRIA; MEDIATORS; PATHWAYS;
D O I
10.3390/ijms131012939
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Autophagy is a self-degradative process that involves turnover and recycling of cytoplasmic components in healthy and diseased tissue. Autophagy has been shown to be protective at the early stages of programmed cell death but it can also promote apoptosis under certain conditions. Earlier we demonstrated that oxygen contributes to the pathogenesis of neonatal brain damage, which can be ameliorated by intervention with recombinant human erythropoietin (rhEpo). Extrinsic- and intrinsic apoptotic pathways are involved in oxygen induced neurotoxicity but the role of autophagy in this model is unclear. We analyzed the expression of autophagy activity markers in the immature rodent brain after exposure to elevated oxygen concentrations. We observed a hyperoxia-exposure dependent regulation of autophagy-related gene (Atg) proteins Atg3, 5, 12, Beclin-1, microtubule-associated protein 1 light chain 3 (LC3), LC3A-II, and LC3B-II which are all key autophagy activity proteins. Interestingly, a single injection with rhEpo at the onset of hyperoxia counteracted these oxygen-mediated effects. Our results indicate that rhEpo generates its protective effect by modifying the key autophagy activity proteins.
引用
收藏
页码:12939 / 12951
页数:13
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