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Neuroprotective mechanisms of heme oxygenase

Neuroprotective mechanisms of heme oxygenase

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中国神经科学学会第四次会员代表大会暨第七届全国学术会议

作者： david gius Gabriele V.RONNETT Radiation Oncology Branch Radiation Oncology Sciences ProgramNational Cancer InstituteNational Institutes of HealthBethesdaMD 20892USA Department of Neuroscience The Johns Hopkins University School of MedicineBaltimoreMD 21205USA

＜正＞Heme oxygenase（HO） enzymes catalyze the breakdown of heme to iron,carbon monoxide（CO）,and biliverdin, which is rapidly converted to ***-1 is an inducible isoform that is known to provide protection against oxidative stress,whereas HO-2 and HO-3 constitutively ***-2 is the predominant isoform expressed in the brain under normal ***-2 has been implicated in protection against oxidative stress,ischemia,and traumatic brain injury. The neuroprotective effects of HO-2 have been attributed to the generation of bilirubin,which is an important radical ***,the mechanism by which HO-2 protection is *** utilized the olfactory system as a model to define the roles of HO-2 in glutathione depletion-induced oxidative injury,as olfactory receptor neurons（ORNs） express high levels of HO *** demostrated that L-buthionine-[S.R.]-sulfoximine（BSO）,an inhibitor of glutathione biosynthase,lowered glutathione levels and induced apoptosis of *** the presence of HO-1 in ORNs,HO-2 null animals displayed increased levels of neuronal death afer BSO treatment compared to wild type *** of bilirubin and cGMP were also reduced in HO-2 null *** used primary olfactory neuron culture as a model;study if neuroprotective mechanisms of HO are regulated by *** found HO inhibitor（SnPPIX） induced neuron death, bilirubin level also *** could reverse the neurotoxic actions of HO inhibitor *** further investigate the molecular mechanisms of CO-cyclic GMP pathway to protect neruons from glutathione depletion-induced oxidative *** of cGMP level decreased in ORNs of HO-2 null mice after BSO *** olfactory primary culture,HO inhibitor SnPPIX and BSO induced ORN apoptosis,levels of cGMP also decreased;A cGMP analog,8-Br-cGMP could reverse the effects of SnPPIX and BSO on neuronal *** investigation showed extracellular-regulated kinase （ERK） phosphorylation might be downstream

关键词： heme oxygenase-2 oxidative stress bilirubin cyclic GMP olfaction

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