PMC:5623723 / 39986-42861 JSONTXT

{"target":"http://pubannotation.org/docs/sourcedb/PMC/sourceid/5623723","sourcedb":"PMC","sourceid":"5623723","source_url":"https://www.ncbi.nlm.nih.gov/pmc/5623723","text":"Strong evidence has shown that LBP exhibits neuroprotective effects through anti-oxidative stress pathways or by inhibiting JNK signaling in different injury models (Li et al., 2013; Xing et al., 2016). In ischemic models, LBP reduced infarct area and ameliorated neurological dysfunction in MCAO mice through anti-apoptotic mechanisms and protection of blood brain barrier (Yang et al., 2012; Wang T. et al., 2014). Although it has been reported that LBP can antagonizes glutamate toxicity on neurons through the JNK pathway (Ho et al., 2009), here we first reported that LBP exerts its neuroprotective effect by modulating both NR2A and NR2B expression and their signaling pathways. The regulation on these two pathways by LBP is not likely to occur at mild OGD when their protein expression is stable, but LBP exerts its effect during severe OGD/ischemia which causes changes in expression of proteins in these pathways. During mild injury (1 h OGD), expression of PSD95, Bad, cytC and cleaved caspase-3 in the NR2B signaling pathway did not change while NR2B and nNOS levels increased. Interestingly, administration of LBP only reduced expression of NR2B and nNOS but did not affect expression of other proteins in the pathway. It is currently unknown on the underlying mechanisms. It will be interesting to further investigate whether LBP regulates protein turnover of NR2B and nNOS through post-translational modification or directly regulates transcription of these genes. Concerning NR2A signaling in response to mild OGD, LBP application did not modify NR2A and pCREB levels as indicated by lack of alteration in their expression. As for pAkt expression, administration of LBP for 1 h under OGD conditions could not upregulate its expression when it was reduced at this time point. It has been reported that NMDA induces maximal activation of Akt phosphorylation at 3 h (Zhu et al., 2002). Therefore, we speculate that LBP upregulates expression of pAkt by increasing the protein expression of NR2A. This is supported by our observation that when exposed to severe injury (4 h OGD), LBP treatment significantly increased expression of NR2A, pCREB and pAkt when the expression of these proteins was decreased. LBP treatment also markedly blocked the increase in expression of major proteins in the NR2B signaling pathway such as nNOS, Bad, cytC and c-caspase-3 under 4 h OGD conditions. We cannot rule out the possibility that LBP can reduce NR2B expression under this condition. However, when NR2B level has already been markedly reduced during this period, LBP did not further inhibit NR2B expression. The reduced expression of NR2B at 4 h and 8 h OGD may be caused by a compensatory mechanism responding to the increased level of NR2B at early stage of OGD (1 h). Therefore, the inhibited effect of LBP on NR2B expression mainly occurred in the early stage of OGD.","tracks":[{"project":"2_test","denotations":[{"id":"29021742-23894366-32379627","span":{"begin":177,"end":181},"obj":"23894366"},{"id":"29021742-27033360-32379628","span":{"begin":196,"end":200},"obj":"27033360"},{"id":"29021742-22438957-32379629","span":{"begin":388,"end":392},"obj":"22438957"},{"id":"29021742-24595452-32379630","span":{"begin":410,"end":414},"obj":"24595452"},{"id":"29021742-19499323-32379631","span":{"begin":538,"end":542},"obj":"19499323"},{"id":"29021742-12373512-32379632","span":{"begin":1892,"end":1896},"obj":"12373512"}],"attributes":[{"subj":"29021742-23894366-32379627","pred":"source","obj":"2_test"},{"subj":"29021742-27033360-32379628","pred":"source","obj":"2_test"},{"subj":"29021742-22438957-32379629","pred":"source","obj":"2_test"},{"subj":"29021742-24595452-32379630","pred":"source","obj":"2_test"},{"subj":"29021742-19499323-32379631","pred":"source","obj":"2_test"},{"subj":"29021742-12373512-32379632","pred":"source","obj":"2_test"}]},{"project":"MyTest","denotations":[{"id":"29021742-23894366-32379627","span":{"begin":177,"end":181},"obj":"23894366"},{"id":"29021742-27033360-32379628","span":{"begin":196,"end":200},"obj":"27033360"},{"id":"29021742-22438957-32379629","span":{"begin":388,"end":392},"obj":"22438957"},{"id":"29021742-24595452-32379630","span":{"begin":410,"end":414},"obj":"24595452"},{"id":"29021742-19499323-32379631","span":{"begin":538,"end":542},"obj":"19499323"},{"id":"29021742-12373512-32379632","span":{"begin":1892,"end":1896},"obj":"12373512"}],"namespaces":[{"prefix":"_base","uri":"https://www.uniprot.org/uniprot/testbase"},{"prefix":"UniProtKB","uri":"https://www.uniprot.org/uniprot/"},{"prefix":"uniprot","uri":"https://www.uniprot.org/uniprotkb/"}],"attributes":[{"subj":"29021742-23894366-32379627","pred":"source","obj":"MyTest"},{"subj":"29021742-27033360-32379628","pred":"source","obj":"MyTest"},{"subj":"29021742-22438957-32379629","pred":"source","obj":"MyTest"},{"subj":"29021742-24595452-32379630","pred":"source","obj":"MyTest"},{"subj":"29021742-19499323-32379631","pred":"source","obj":"MyTest"},{"subj":"29021742-12373512-32379632","pred":"source","obj":"MyTest"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"2_test","color":"#93ecd0","default":true},{"id":"MyTest","color":"#ecb693"}]}]}}