Autophagy in neonatal hypoxia ischemic brain is associated with oxidative stress.

作者: Qing Lu , Valerie A. Harris , Sanjv Kumar , Heidi M. Mansour , Stephen M. Black

DOI: 10.1016/J.REDOX.2015.06.016

关键词:

摘要: Autophagy is activated when the neonatal brain exposed to hypoxia ischemia (HI), but mechanisms underlying its activation and role in neuronal cell death associated with HI unclear. We have previously shown that reactive oxygen species (ROS) derived from nicotinamide adenine dinucleotide phosphate (NADPH) oxidase play an important HI-mediated death. Thus, aim of this study was determine if ROS involved autophagy injury a protective or deleterious pathway. Initial electron microscopy data demonstrated autophagosome formation elevated P7 hippocampal slice cultures oxygen-glucose deprivation (OGD). This corresponded increased levels LC3II mRNA protein. The inhibitor, 3-methyladenine (3-MA) effectively reduced OGD. Neuronal significantly attenuated. Finally, we found pharmacologic inhibition NADPH using apocynin gp91ds-tat decreased rat respectively. our results suggest contributes oxidative stress dependent.

参考文章(45)
Seymour Levine, Anoxic-Ischemic Encephalopathy in Rats American Journal of Pathology. ,vol. 36, pp. 1- 17 ,(1960)
Chunli Liu, Yanqin Gao, John Barrett, Bingren Hu, Autophagy and protein aggregation after brain ischemia Journal of Neurochemistry. ,vol. 115, pp. 68- 78 ,(2010) , 10.1111/J.1471-4159.2010.06905.X
Xiaoting Wu, Hyeran Won, David C. Rubinsztein, Autophagy and mammalian development Biochemical Society Transactions. ,vol. 41, pp. 1489- 1494 ,(2013) , 10.1042/BST20130185
T Nitatori, N Sato, S Waguri, Y Karasawa, H Araki, K Shibanai, E Kominami, Y Uchiyama, Delayed neuronal death in the CA1 pyramidal cell layer of the gerbil hippocampus following transient ischemia is apoptosis The Journal of Neuroscience. ,vol. 15, pp. 1001- 1011 ,(1995) , 10.1523/JNEUROSCI.15-02-01001.1995
Qing Lu, Thomas F. Rau, Valerie Harris, Maribeth Johnson, David J. Poulsen, Stephen M. Black, Increased p38 mitogen‐activated protein kinase signaling is involved in the oxidative stress associated with oxygen and glucose deprivation in neonatal hippocampal slice cultures European Journal of Neuroscience. ,vol. 34, pp. 1093- 1101 ,(2011) , 10.1111/J.1460-9568.2011.07786.X
R. M. Blumberg, E. B. Cady, J. S. Wigglesworth, J. E. McKenzie, A. D. Edwards, Relation between delayed impairment of cerebral energy metabolism and infarction following transient focal hypoxia-ischaemia in the developing brain. Experimental Brain Research. ,vol. 113, pp. 130- 137 ,(1997) , 10.1007/BF02454148
SC Roth, J. Baudin, E. Cady, K. Johal, JP Townsend, J S. Wyatt, E O R. Reynolds, A L. Stewart, Relation of deranged neonatal cerebral oxidative metabolism with neurodevelopmental outcome and head circumference at 4 years Developmental Medicine & Child Neurology. ,vol. 39, pp. 718- 725 ,(2008) , 10.1111/J.1469-8749.1997.TB07372.X
Long Chen, Baoshan Xu, Lei Liu, Yan Luo, Hongyu Zhou, Wenxing Chen, Tao Shen, Xiuzhen Han, Christopher D. Kontos, Shile Huang, Cadmium induction of reactive oxygen species activates the mTOR pathway, leading to neuronal cell death. Free Radical Biology and Medicine. ,vol. 50, pp. 624- 632 ,(2011) , 10.1016/J.FREERADBIOMED.2010.12.032
A Terman, B Gustafsson, UT Brunk, Autophagy, organelles and ageing. The Journal of Pathology. ,vol. 211, pp. 134- 143 ,(2007) , 10.1002/PATH.2094
Kannan Kunchithapautham, Bärbel Rohrer, Apoptosis and autophagy in photoreceptors exposed to oxidative stress. Autophagy. ,vol. 3, pp. 433- 441 ,(2007) , 10.4161/AUTO.4294