Norepinephrine increases the monoamine oxidase A and oxidative stress in SH-SY5Y cells

Abstract

BACKGROUND: Obstructive sleep apnea (OSA) is a major breathing disorder affecting 5-7% of adult population, which increases risks for stroke and cardiovascular morbidities and mortalities. Episodes of oxygen desaturation caused by obstruction of the airway of OSA patients manifested as intermittent hypoxia (IH) significantly contributes to the excessive production of reactive oxygen species, which cause oxidative stress and inflammation in the pathogenesis of cardiovascular disease. Also, OSA patients are reportedly with elevated levels of sympathetic and norepinephrine (NE) activities. Monoamine oxidase isoform-A (MAO-A) deaminates NE and produces H2O2 as a byproduct during its catalytic reaction. Additionally, 2,3-dioxygenase (IDO) is closely associated with oxidative stress and inflammation [5]. We recently observed that inhibition of MAO-A decreases the IH-induced cell death in SH-SY5Y cells. AIMS AND OBJECTIVES: We aim to examine the role of NE in the IH-induced cell death. In this study, we test the hypothesis that NE could increase the expression of MAO-A and IDO in SH-SY5Y cells. METHODS: Cultured SH-SY5Y cells were used in this study, which constitutively express MAO-A but not MAO-B. Cells were treated with NE at concentrations of 0.01 μM and 0.1 μM to mimic the NE overspill in OSA patients. Clorgyline (10 μM) was used as a selective inhibitor of MAO-A; Western blotting was used to assess the level of protein expression of MAOA, IDO and antioxidant enzyme superoxide dismutase (SOD2). Also, GSSG/GSH ratio was obtained to evaluate the level of oxidative stress. RESULTS: We found significant increased levels of MAO-A and IDO expressions in the SH-SY5Y cells treated with NE (0.01 μM and 0.1 μM) for 48 hours. In addition, the ratio of GSSG/GSH was significantly increased and the level of SOD2 expression was decreased by the NE treatment, suggesting an elevated level of oxidative stress. Furthermore, the effects of NE on MAO-A and IDO expression and oxidative stress were partially antagonized by 10 μM clorgyline. CONCLUSION: The overspill of NE in the OSA patient could worsen the IH-induced oxidative stress and inflammation via increased levels of MAO-A and IDO expression, which may play a mechanistic role in the pathophysiological response to chronic intermittent hypoxia.