Noradrenaline increases intracellular glutathione in human astrocytoma U-251 MG cells by inducing glutamate-cysteine ligase protein via β₃-adrenoceptor stimulation

详细信息    查看全文

• 作者：Yasuhiro Yoshioka ; ^{yoshioka@pharm.setsunan.ac.jp" class="auth_mail" title="E-mail the corresponding author} ; Hisatsugu Kadoi ^{12d404kh@edu.setsunan.ac.jp" class="auth_mail" title="E-mail the corresponding author} ; Akiko Yamamuro ^{yamamuro@pharm.setsunan.ac.jp" class="auth_mail" title="E-mail the corresponding author} ; Yuki Ishimaru ^{ishimaru@pharm.setsunan.ac.jp" class="auth_mail" title="E-mail the corresponding author} ; Sadaaki Maeda ^{smaeda@pharm.setsunan.ac.jp" class="auth_mail" title="E-mail the corresponding author}
• 关键词：AD ; Alzheimer's disease ; ERK ; extracellular signal-regulated kinase ; GCLc ; catalytic subunit of glutamate-cysteine ligase ; CNS ; central nervous system ; DTNB ; 5 ; 5&prime ; -dithio-bis(2-nitrobenzoic acid) ; JNK ; c-Jun N-terminal kinase ; GSH ; glutathione ; MEK1 ; mitogen-activated protein/ERK kinase 1 ; PD ; Parkinson's disease
• 刊名：European Journal of Pharmacology
• 出版年：2016
• 出版时间：5 February 2016
• 年：2016
• 卷：772
• 期：Complete
• 页码：51-61
• 全文大小：778 K

文摘

Glutathione (GSH) plays a critical role in protecting cells from oxidative damage. Since neurons rely on the supply of GSH from astrocytes to maintain optimal intracellular GSH concentrations, the GSH concentration of astrocytes is important for the survival of neighboring neurons against oxidative stress. The neurotransmitter noradrenaline is known to modulate the functions of astrocytes and has been suggested to have neuroprotective properties in neurodegenerative diseases. To elucidate the mechanisms underlying the neuroprotective properties of noradrenaline, in this study, we investigated the effect of noradrenaline on the concentrations of intracellular GSH in human U-251 malignant glioma (MG; astrocytoma) cells. Treatment of the cells with noradrenaline for 24 h concentration-dependently increased their intracellular GSH concentration. This increase was inhibited by a non-selective β-adrenoceptor antagonist propranolol and by a selective β₃-adrenoceptor antagonist SR59230A, but not by a non-selective α-adrenoceptor antagonist phenoxybenzamine, or by a selective β₁-adrenoceptor antagonist atenolol or by a selective β₂-adrenoceptor antagonist butoxamine. In addition, the selective β₃-adrenoceptor agonist CL316243 increased the intracellular GSH in U-251 MG cells. Treatment of the cells with noradrenaline (10 μM) for 24 h increased the protein level of the catalytic subunit of glutamate-cysteine ligase (GCLc), the rate-limiting enzyme of GSH synthesis; and this increase was inhibited by SR59230A. These results thus suggest that noradrenaline increased the GSH concentration in astrocytes by inducing GCLc protein in them via β₃-adrenoceptor stimulation.