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Noradrenaline protects neurons against H 2 O 2 ‐induced death by increasing the supply of glutathione from astrocytes via β 3 ‐adrenoceptor stimulation
Author(s) -
Yoshioka Yasuhiro,
Negoro Ryosuke,
Kadoi Hisatsugu,
Motegi Toshiki,
Shibagaki Fumiya,
Yamamuro Akiko,
Ishimaru Yuki,
Maeda Sadaaki
Publication year - 2021
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.24733
Subject(s) - neuroprotection , glutathione , buthionine sulfoximine , astrocyte , neurotoxicity , oxidative stress , sh sy5y , stimulation , programmed cell death , pharmacology , intracellular , biology , chemistry , cell culture , microbiology and biotechnology , endocrinology , medicine , biochemistry , central nervous system , neuroblastoma , apoptosis , toxicity , genetics , enzyme
Oxidative stress has been implicated in a variety of neurodegenerative disorders, such as Alzheimer's and Parkinson's disease. Astrocytes play a significant role in maintaining survival of neurons by supplying antioxidants such as glutathione (GSH) to neurons. Recently, we found that noradrenaline increased the intracellular GSH concentration in astrocytes via β 3 ‐adrenoceptor stimulation. These observations suggest that noradrenaline protects neurons from oxidative stress‐induced death by increasing the supply of GSH from astrocytes to neurons via the stimulation of β 3 ‐adrenoceptor in astrocytes. In the present study, we examined the protective effect of noradrenaline against H 2 O 2 ‐induced neurotoxicity using two different mixed cultures: the mixed culture of human astrocytoma U‐251 MG cells and human neuroblastoma SH‐SY5Y cells, and the mouse primary cerebrum mixed culture of neurons and astrocytes. H 2 O 2 ‐induced neuronal cell death was significantly attenuated by pretreatment with noradrenaline in both mixed cultures but not in single culture of SH‐SY5Y cells or in mouse cerebrum neuron‐rich culture. The neuroprotective effect of noradrenaline was inhibited by SR59230A, a selective β 3 ‐adrenoceptor antagonist, and CL316243, a selective β 3 ‐adrenoceptor agonist, mimicked the neuroprotective effect of noradrenaline. DL‐buthionine‐[S,R]‐sulfoximine, a GSH synthesis inhibitor, negated the neuroprotective effect of noradrenaline in both mixed cultures. MK571, which inhibits the export of GSH from astrocytes mediated by multidrug resistance‐associated protein 1, also prevented the neuroprotective effect of noradrenaline. These results suggest that noradrenaline protects neurons against H 2 O 2 ‐induced death by increasing the supply of GSH from astrocytes via β 3 ‐adrenoceptor stimulation.