Aripiprazole increases NAD(P)H–quinone oxidoreductase-1 and heme oxygenase-1 in PC12 cells

• Published in: Journal of Neural Transmission 2015-06, Vol.122 (6), p.757-772
• Main Authors: Kaneko, Yoko S., Takayanagi, Takeshi, Nagasaki, Hiroshi, Kodani, Yu, Nakashima, Akira, Mori, Keiji, Suzuki, Atsushi, Itoh, Mitsuyasu, Kondo, Kazunao, Nagatsu, Toshiharu, Ota, Miyuki, Ota, Akira
• Format: Article
• Language: English
• Subjects: Acetylation - drug effects; Animals; Antipsychotic Agents - pharmacology; Aripiprazole - pharmacology; beta-Transducin Repeat-Containing Proteins - metabolism; Cell Nucleus - drug effects; Cell Nucleus - enzymology; Cell Survival - drug effects; Cytosol - drug effects; Cytosol - enzymology; Glutamate-Cysteine Ligase - metabolism; Heme Oxygenase (Decyclizing) - metabolism; Hydrogen Peroxide - toxicity; Intracellular Signaling Peptides and Proteins - metabolism; Kelch-Like ECH-Associated Protein 1; Medicine; Medicine & Public Health; NAD(P)H Dehydrogenase (Quinone) - metabolism; Neurology; Neurosciences; NF-E2-Related Factor 2 - metabolism; PC12 Cells; Phosphorylation - drug effects; Psychiatry; Rats; Translational Neurosciences - Original Article
• ISSN: 0300-9564; 1435-1463
• DOI: 10.1007/s00702-014-1350-8

We previously showed that aripiprazole increases intracellular NADPH and glucose - 6 - phosphate dehydrogenase mRNA in PC12 cells. Aripiprazole presumably activates a system that concurrently detoxifies reactive oxygen species and replenishes NADPH. Nrf2, a master transcriptional regulator of redox homeostasis genes, also activates the pentose phosphate pathway, including NADPH production. Therefore, our aim was to determine whether aripiprazole activates Nrf2 in PC12 cells. Aripiprazole increased mRNA expression of Nrf2-dependent genes ( NAD(P)H – quinone oxidoreductase - 1 , Nqo1 ; heme oxygenase - 1 , HO1 ; and glutamate - cysteine ligase catalytic subunit ) and protein expression of Nqo1 and HO1 in these cells ( p