Nicotinamide pre-treatment ameliorates NAD(H) hyperoxidation and improves neuronal function after severe hypoxia.
Nicotinamide pre-treatment ameliorates NAD(H) hyperoxidation and improves neuronal function after severe hypoxia.
复制标题
DOI：
10.1016/j.nbd.2013.10.025
复制
发表时间：
2014-02
影响因子：
6.1
通讯作者：
Turner, Dennis A.
中科院分区：
文献类型：
--
作者：
Shetty, Pavan K.;Galeffi, Francesca;Turner, Dennis A.
Prolonged hypoxia leads to irreversible loss of neuronal function and metabolic impairment of nicotinamide adenine dinucleotide recycling (between NAD+ and NADH) immediately after reoxygenation, resulting in NADH hyperoxidation. We test whether addition of nicotinamide (to enhance NAD+ levels) or PARP-1 inhibition (to prevent consumption of NAD+) can be effective in improving either loss of neuronal function or hyperoxidation following severe hypoxic injury in hippocampal slices. After severe, prolonged hypoxia (maintained for 3 min after spreading depression) there was hyperoxidation of NADH following reoxygenation, an increased soluble NAD+/NADH ratio, loss of neuronal field excitatory post-synaptic potential (fEPSP) and decreased ATP content. Nicotinamide incubation (5 mM) 2 hr prior to hypoxia significantly increased total NAD(H) content, improved neuronal recovery, enhanced ATP content, and prevented NADH hyperoxidation. The nicotinamide-induced increase in total soluble NAD(H) was more significant in the cytosolic compartment than within mitochondria. Prolonged incubation with PJ-34 (>1hr) led to enhanced baseline NADH fluorescence prior to hypoxia, as well as improved neuronal recovery, NADH hyperoxidation and ATP content on recovery from severe hypoxia and reoxygenation. In this acute model of severe neuronal dysfunction prolonged incubation with either nicotinamide or PJ-34 prior to hypoxia improved recovery of neuronal function, enhanced NADH reduction and ATP content, but neither treatment restored function when administered during or after prolonged hypoxia and reoxygenation.
登录
查看更多内容
影响因子：
3.7
作者：
Kim SH;Lu HF;Alano CC
通讯作者：
Alano CC
影响因子：
4.8
作者：
Kirsch, M;De Groot, H
通讯作者：
De Groot, H
影响因子：
12.4
作者：
Moroni, F;Meli, E;Pellegrini-Giampietro, DE
通讯作者：
Pellegrini-Giampietro, DE
影响因子：
4.2
作者：
Clark, Robert S. B.;Vagni, Vincent A.;Szabo, Csaba
通讯作者：
Szabo, Csaba
影响因子：
--
作者：
Hoane MR;Pierce JL;Kaufman NA;Beare JE
通讯作者：
Beare JE