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Depression: 21st Century Solutions + The Dark Side of Wheat

Article Publish Status: FREE
Abstract Title:

Glutamate induces mitochondrial dynamic imbalance and autophagy activation: preventive effects of selenium.

Abstract Source:

PLoS One. 2012 ;7(6):e39382. Epub 2012 Jun 19. PMID: 22724008

Abstract Author(s):

Santosh Kumari, Suresh L Mehta, P Andy Li

Article Affiliation:

Department of Pharmaceutical Sciences, Biomanufacturing Research Institute and Technology Enterprise, North Carolina Central University, Durham, North Carolina, USA.

Abstract:

Glutamate-induced cytotoxicity is partially mediated by enhanced oxidative stress. The objectives of the present study are to determine the effects of glutamate on mitochondrial membrane potential, oxygen consumption, mitochondrial dynamics and autophagy regulating factors and to explore the protective effects of selenium against glutamate cytotoxicity in murine neuronal HT22 cells. Our results demonstrated that glutamate resulted in cell death in a dose-dependent manner and supplementation of 100 nM sodium selenite prevented the detrimental effects of glutamate on cell survival. The glutamate induced cytotoxicity was associated with mitochondrial hyperpolarization, increased ROS production and enhanced oxygen consumption. Selenium reversed these alterations. Furthermore, glutamate increased the levels of mitochondrial fission protein markers pDrp1 and Fis1 and caused increase in mitochondrial fragmentation. Selenium corrected the glutamate-caused mitochondrial dynamic imbalance and reduced the number of cells with fragmented mitochondria. Finally, glutamate activated autophagy markers Beclin 1 and LC3-II, while selenium prevented the activation. These results suggest that glutamate targets the mitochondria and selenium supplementation within physiological concentration is capable of preventing the detrimental effects of glutamate on the mitochondria. Therefore, adequate selenium supplementation may be an efficient strategy to prevent the detrimental glutamate toxicity and further studies are warranted to define the therapeutic potentials of selenium in animal disease models and in human.

Study Type : Animal Study

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Sayer Ji
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Depression: 21st Century Solutions + The Dark Side of Wheat

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