环磷酸鸟苷（cGMP）可防止大鼠中缺乏营养因子的运动神经元中神经元型一氧化氮合酶的表达及细胞凋亡。

Cyclic guanosine 5' monophosphate (GMP) prevents expression of neuronal nitric oxide synthase and apoptosis in motor neurons deprived of trophic factors in rats.

作者信息

Estévez Alvaro G, Kamaid Andrés, Thompson J Anthony, Cornwell Trudy L, Radi Rafael, Barbeito Luis, Beckman Joseph S

机构信息

Department of Physiology and Biophysics, University of Alabama at Birmingham, 1918 University Boulevard, MCLM 850, Birmingham, AL 35294-0005, USA.

出版信息

Neurosci Lett. 2002 Jul 5;326(3):201-5. doi: 10.1016/s0304-3940(02)00341-5.

DOI:10.1016/s0304-3940(02)00341-5

PMID:12095656

Abstract

Deprivation of trophic factors induces expression of neuronal nitric oxide synthase (NOS) and nitric oxide production in cultured motor neurons, leading to apoptosis. Motor neuron apoptosis requires the simultaneous production of nitric oxide and superoxide and is associated with increased nitrotyrosine immunoreactivity. Nitric oxide also stimulates cyclic guanosine 5' monophosphate (cGMP) synthesis, which enhances the survival of motor neurons treated with brain derived trophic factor (BDNF). Here we report that cGMP analogs blocked neuronal NOS induction, nitrotyrosine accumulation, and prevented apoptosis for up to 3 day of motor neurons deprived of trophic factors. Low concentrations of exogenous nitric oxide (<100 nM), which are not toxic for BDNF-treated cultures, reversed the protective effect of cGMP. These results suggest that elevation of cGMP could decrease nitric oxide production, and thereby preventing motor neuron apoptosis.

摘要

营养因子的剥夺会诱导培养的运动神经元中神经元型一氧化氮合酶（NOS）的表达和一氧化氮的产生，从而导致细胞凋亡。运动神经元凋亡需要同时产生一氧化氮和超氧化物，并且与硝基酪氨酸免疫反应性增加有关。一氧化氮还刺激环磷酸鸟苷（cGMP）的合成，这增强了用脑源性神经营养因子（BDNF）处理的运动神经元的存活。在这里我们报告，cGMP类似物可阻断神经元NOS的诱导、硝基酪氨酸的积累，并在营养因子剥夺的运动神经元中长达3天预防细胞凋亡。低浓度的外源性一氧化氮（<100 nM）对BDNF处理的培养物无毒，可逆转cGMP的保护作用。这些结果表明，cGMP的升高可减少一氧化氮的产生，从而预防运动神经元凋亡。