跳至主要内容

Astrocytes Prevent Ethanol Induced Apoptosis of Nrf2 Depleted Neurons by Maintaining GSH Homeostasis

Glutathione (GSH), a major cellular antioxidant, is the most abundant intracellular non-protein thiol and anti-oxidant in the body with a concentration of approximately 2 - 3 mM in brain. It can protect cells against oxidative stress injury. It is also vital for guarding normal healthy metabolism as well as defense against a range of disease and toxicity mechanisms by appropriately controlling cellular redox levels, most notably in the central nervous system (CNS).

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. In various experimental models of neurodegeneration, neuronal antioxidant defenses (mainly GSH) have been shown to be supported by astrocytes. The authors therefore sought to determine whether astrocytes could render protection to neurons against ethanol (ETOH) toxicity, particularly when the function of Nrf2 was compromised in neurons.

The experimental model consisted of co-culturing PCAs with Nrf2 downregulated PCNs that were exposed with and without 4 mg/mL ETOH for 24 h. Monochlorobimane (MCB) staining followed by FACS analysis showed that astrocytes blocked ETOH induced GSH decrement in Nrf2-silenced neurons as opposed to exaggerated GSH depletion in Nrf2 downregulated PCNs alone. Similarly, the heightened activation of caspase 3/7 observed in Nrf2-compromised neurons was attenuated when co-cultured with astrocytes as measured by luminescence based caspase Glo assay. Furthermore, annexin-V-FITC staining followed by FACS analysis revealed that Nrf2 depleted neurons showed resistance to ETOH induced neuronal apoptosis when co-cultured with astrocytes.

In conclusion, the current study identified a neuroprotective role for cortical astrocytes against ETOH even under a condition when neurons were partially depleted of Nrf2 based antioxidant machinery. Another important finding of the study was that this neuroprotective effect of astrocyte despite partially compromised neuronal Nrf2 could be achieved by GSH supply, a central component mediating redox signaling and cell death progression.

Article by Madhusudhanan Narasimhan, et al, from Texas Tech University Health Sciences Center, Lubbock, USA.

Full access: http://mrw.so/JPleh

Image by wcaprunner, from Flickr-cc.

评论

发表评论

此博客中的热门博文

Does Immigration Promote the Investment of the Monopolistic Firm?

In the present paper, we examine the effect of increasing uncertainty of immigrants’ growth on the optimal timing of investment of a firm that has a monopolistic power over the labor market. It is revealed that when the uncertainty of immigrants’ growth is more than a threshold level, increasing uncertainty of immigrants’ growth accelerates the optimal timing of firms’ investment and enhances the economic growth, even if the uncertainty of immigrants’ growth is formulated by the geometric Brownian motion, which is in sharp contrast to the standard result that an increase in the uncertainty postpones the optimal timing. With an increase in the immigrants over the past ten years, workforces in the host countries have been growing significantly to the extent that the immigrants represent 70% of the increase in the workforce in Europe, and 47% in the United States as OECD indicates. In the present paper, we attempted to investigate the effect of increased uncertainty caused by the growi...
发表评论
阅读全文

Education Policy Implementation: A Mechanism for Enhancing Primary Education Development in Zanzibar

Education is one of the fundamental rights of individuals; therefore, the government of a country needs to develop and strengthen educational policy and quality as well as to ensure that everyone has equal access to basic education. The improvement of access and quality of education in the world is becoming as an essential factor in development, whereas the basic education (primary school), is acknowledged as a foundation of the higher educational development for every country. To fulfill this goal, governments introduce several policies and procedures; however, it requires some reforms and participation from the politician, policymakers, and other stakeholders to re-examine educational policy so that it can lead to multiplication and betterment of the reforms. Educational reforms actually focus on accountability. A positive educational development and reform is very challenging and needs more effort and strategy on how to use and utilize the resources effectively as such it can achie...
发表评论
阅读全文