期刊
FREE RADICAL BIOLOGY AND MEDICINE
卷 49, 期 11, 页码 1815-1821出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.freeradbiomed.2010.09.017
关键词
Neuroprotection; PNU282987; Heme oxygenase 1; Nicotinic receptors; Free radicals
资金
- Spanish Ministry of Science and Innovation [SAF2009-12150]
- Spanish Ministry of Health (Instituto de Salud Carlos III) [RETICS-RD06/0026]
- Comunidad Autonoma de Madrid [SAL2006/0275]
- Fundacion CIEN IS Carlos III MICINN [PI016/09]
- Agencia Lain Entralgo [NDE07/09]
- Comunidad de Madrid Spain
Most neuroprotection studies with nicotinic agonists have shown efficacy when given before the stressor Here WE have investigated whether the ea nicotinic acetylcholine receptor (nAChR) agonist PNU282987 can prevent cell death once the cells have already undergone an oxidative stress The combination of rotenone (30 mu M) plus oligomycin A (10 mu M) (rot/oligo) has been used as an in vitro model of mitochondrial ROS production SH SY5Y cells incubated with rot/oligo for 8 h and left for another 16 h in MEM/F 12 experienced 30% apoptotic cell death Under these experimental conditions PNU282987 administered after rot/oligo (PST/PNU) prevented cell death in a concentration-dependent manner Co incubation of PNU282987 with 100 nM methyllycaconitine (a selective alpha nAChR antagonist) 10 mu M mecamylamine (a nonselective nAChR antagonist) 3 mu M LY294002 (a PI3K inhibitor) or 10 mu M AG490 (a Jak2 inhibitor) prevented the protection afforded by PST/PNU Moreover the increase in ROS active caspase-3 and apoptosis caused by rot/oligo was also prevented by PST/PNU Furthermore PNU282987 increased the expression of heme oxygenase-1 (HO 1) a critical cell defense enzyme against oxidative stress this Increase was prevented by AG490 or LY294002 The HO 1 inhibitor Sn(IV) protoporphyrin-IX also inhibited the PST/PNU protecting effects These results suggest that activation of ea nAChR linked to the Jak2/PI3K/Akt cascade induces the antioxidant enzyme HO 1 tc provide neuroprotection (C) 2010 Elsevier Inc All rights reserved
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据