The Effects of NAD+ on Apoptotic Neuronal Death and Mitochondrial Biogenesis and Function after Glutamate Excitotoxicity

International Journal of Molecular Sciences

Xiaowan Wang²  Hailong Li²  Shinghua Ding¹ 

[1] Dalton Cardiovascular Research Center, Department of Bioengineering, University of Missouri, Columbia, MO 65211, USA;

关键词: ischemic stroke;    glutamate excitotoxicity;    apoptosis;    AIF;    mitochondrial biogenesis;   

DOI  :  10.3390/ijms151120449

来源: mdpi

【 摘 要 】

NAD⁺ is an essential co-enzyme for cellular energy metabolism and is also involved as a substrate for many cellular enzymatic reactions. It has been shown that NAD⁺ has a beneficial effect on neuronal survival and brain injury in in vitro and in vivo ischemic models. However, the effect of NAD⁺ on mitochondrial biogenesis and function in ischemia has not been well investigated. In the present study, we used an in vitro glutamate excitotoxicity model of primary cultured cortical neurons to study the effect of NAD⁺ on apoptotic neuronal death and mitochondrial biogenesis and function. Our results show that supplementation of NAD⁺ could effectively reduce apoptotic neuronal death, and apoptotic inducing factor translocation after neurons were challenged with excitotoxic glutamate stimulation. Using different approaches including confocal imaging, mitochondrial DNA measurement and Western blot analysis of PGC-1 and NRF-1, we also found that NAD⁺ could significantly attenuate glutamate-induced mitochondrial fragmentation and the impairment of mitochondrial biogenesis. Furthermore, NAD⁺ treatment effectively inhibited mitochondrial membrane potential depolarization and NADH redistribution after excitotoxic glutamate stimulation. Taken together, our results demonstrated that NAD⁺ is capable of inhibiting apoptotic neuronal death after glutamate excitotoxicity via preserving mitochondrial biogenesis and integrity. Our findings provide insights into potential neuroprotective strategies in ischemic stroke.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.