PMC:4536246 / 16348-17713
Annnotations
{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/4536246","sourcedb":"PMC","sourceid":"4536246","source_url":"https://www.ncbi.nlm.nih.gov/pmc/4536246","text":"In this study, we evaluated the simultaneous changes in ADMA levels and DDAH-1 mRNA expression in brain areas in an animal model specific for migraine in order to evaluate whether ADMA-DDAH-pathway may be involved in migraine. We also evaluated nNOS and eNOS expression in the same brain areas, and ADMA levels in the venous blood, drawn from the vena cava. Our findings show that AMDA levels significantly increased in the hypothalamus and medulla 4 h after GTN administration, the timing where we observe neuronal activation and hyperlagesia. This increase was associated to the inhibition of DDAH-1 expression and to the increase in nNOS expression in the same areas. eNOS expression instead was not affected. Taken together, these results suggest that the increase in brain NO availability, secondary to GTN exposure [45], may have interfered with DDAH-1 expression, possibly via S-nitrosylation of DDAH-1 active site [46, 47]. Indeed, deletion of DDAH-1 gene, or the inhibition of its transcription, is associated with an increase of ADMA levels [48]. Alternatively, DDAH-1 expression may have been inhibited via GTN-induced oxidative stress [49] or GTN-induced activation of inflammatory pathway [50, 51]. Previous reports have indeed shown that DDAH activity and protein expression may be markedly reduced during oxidative stress and/or inflammation [52–54].","tracks":[{"project":"TEST0","denotations":[{"id":"26272684-109-115-1511581","span":{"begin":822,"end":824},"obj":"[\"10369185\"]"},{"id":"26272684-210-216-1511582","span":{"begin":923,"end":925},"obj":"[\"12370443\"]"},{"id":"26272684-214-220-1511583","span":{"begin":927,"end":929},"obj":"[\"18796638\"]"},{"id":"26272684-120-126-1511584","span":{"begin":1052,"end":1054},"obj":"[\"22000584\"]"},{"id":"26272684-91-97-1511585","span":{"begin":1148,"end":1150},"obj":"[\"25492827\"]"},{"id":"26272684-146-152-1511586","span":{"begin":1203,"end":1205},"obj":"[\"15936821\"]"},{"id":"26272684-150-156-1511587","span":{"begin":1207,"end":1209},"obj":"[\"19733216\"]"},{"id":"26272684-146-152-1511588","span":{"begin":1358,"end":1360},"obj":"[\"17881609\", \"15915325\", \"20600827\"]"}],"attributes":[{"subj":"26272684-109-115-1511581","pred":"source","obj":"TEST0"},{"subj":"26272684-210-216-1511582","pred":"source","obj":"TEST0"},{"subj":"26272684-214-220-1511583","pred":"source","obj":"TEST0"},{"subj":"26272684-120-126-1511584","pred":"source","obj":"TEST0"},{"subj":"26272684-91-97-1511585","pred":"source","obj":"TEST0"},{"subj":"26272684-146-152-1511586","pred":"source","obj":"TEST0"},{"subj":"26272684-150-156-1511587","pred":"source","obj":"TEST0"},{"subj":"26272684-146-152-1511588","pred":"source","obj":"TEST0"}]},{"project":"2_test","denotations":[{"id":"26272684-10369185-60565609","span":{"begin":822,"end":824},"obj":"10369185"},{"id":"26272684-12370443-60565610","span":{"begin":923,"end":925},"obj":"12370443"},{"id":"26272684-18796638-60565611","span":{"begin":927,"end":929},"obj":"18796638"},{"id":"26272684-22000584-60565612","span":{"begin":1052,"end":1054},"obj":"22000584"},{"id":"26272684-25492827-60565613","span":{"begin":1148,"end":1150},"obj":"25492827"},{"id":"26272684-15936821-60565614","span":{"begin":1203,"end":1205},"obj":"15936821"},{"id":"26272684-19733216-60565615","span":{"begin":1207,"end":1209},"obj":"19733216"},{"id":"26272684-17881609-60565616","span":{"begin":1358,"end":1360},"obj":"17881609"},{"id":"26272684-15915325-60565616","span":{"begin":1358,"end":1360},"obj":"15915325"},{"id":"26272684-20600827-60565616","span":{"begin":1358,"end":1360},"obj":"20600827"}],"attributes":[{"subj":"26272684-10369185-60565609","pred":"source","obj":"2_test"},{"subj":"26272684-12370443-60565610","pred":"source","obj":"2_test"},{"subj":"26272684-18796638-60565611","pred":"source","obj":"2_test"},{"subj":"26272684-22000584-60565612","pred":"source","obj":"2_test"},{"subj":"26272684-25492827-60565613","pred":"source","obj":"2_test"},{"subj":"26272684-15936821-60565614","pred":"source","obj":"2_test"},{"subj":"26272684-19733216-60565615","pred":"source","obj":"2_test"},{"subj":"26272684-17881609-60565616","pred":"source","obj":"2_test"},{"subj":"26272684-15915325-60565616","pred":"source","obj":"2_test"},{"subj":"26272684-20600827-60565616","pred":"source","obj":"2_test"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"TEST0","color":"#93e4ec","default":true},{"id":"2_test","color":"#ecd993"}]}]}}