Astrocytes Prevent Ethanol Induced Apoptosis of Nrf2 Depleted Neurons by Maintaining GSH Homeostasis英文文献资料.docVIP

Open Journal of Apoptosis, 2012, 1, 9-18 /10.4236/ojapo.2012.12002 Published Online July 2012 (http://www.SciRP.org/journal/ojapo) Astrocytes Prevent Ethanol Induced Apoptosis of Nrf2 Depleted Neurons by Maintaining GSH Homeostasis Madhusudhanan Narasimhan George Henderson , Marylatha Rathinam , Dhyanesh Patel , 1,2* 1 1 1,2 1,2* , Lenin Mahimainathan 1 Department of Pharmacology and Neuroscience, Texas Tech University Health Sciences Center, Lubbock, USA South Plains Alcohol and Addiction Research Center, Texas Tech University Health Sciences Center, Lubbock, USA Email: { Received May 14, 2012; revised June 27, 2012; accepted July 12, 2012 2 * lenin.mahimainathan, madhu.narasimhan}@ * ABSTRACT Glutathione (GSH), a major cellular antioxidant protects cells against oxidative stress injury. Nuclear factor erythroid 2-related factor 2 (NFE2L2/Nrf2) is a redox sensitive master regulator of battery of antioxidant enzymes including those involved in GSH antioxidant machinery. Earlier we reported that ethanol (ETOH) elicits apoptotic death of pri- mary cortical neurons (PCNs) which in partly due to depletion of intracellular GSH levels. Further a recent report from our laboratory illustrated that ETOH exacerbated the dysregulation of GSH and caspase mediated cell death of cortical neurons that are compromised in Nrf2 machinery (Narasimhan et al., 2011). In various experimental models of neu- rodegeneration, neuronal antioxidant defenses mainly GSH has been shown to be supported by astrocytes. We therefore sought to determine whether astrocytes can render protection to neurons against ETOH toxicity, particularly when the function of Nrf2 is compromised in neurons. The experimental model consisted of co-culturing primary cortical astro- cytes (PCA) with Nrf2 downregu