Up-regulation of rat adipose tissue adiponectin gene expression by long-term but not by short-term food restriction |
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Authors: | Jacek Turyn Justyna Korczynska Malgorzata Presler Ewa Stelmanska Elzbieta Goyke Julian Swierczynski |
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Institution: | (1) Division of Biomedical Sciences, Edward Via Virginia College of Osteopathic Medicine, Virginia Tech Corporate Research Center, 2265 Kraft Drive, Blacksburg, VA 24060, USA;(2) Division of Toxicology, Department of Environmental Health Sciences, The Johns Hopkins University Bloomberg School of Public Health, 615 North Wolfe Street, Baltimore, MD 21205, USA |
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Abstract: | 3H-1,2-Dithiole-3-thione (D3T), a potent member of dithiolethiones, induces phase 2 enzymes by activating an Nrf2/Keap1-dependent
signaling pathway. It was proposed that interaction between D3T and two adjacent sulfhydryl groups of Keap1 might cause dissociation
of Keap1 from Nrf2, leading to Nrf2 activation. This study was undertaken to investigate the reactions between D3T and thiols,
including the dithiol compound, dithiothreitol (DTT), and the monothiol, glutathione (GSH). We reported here that under physiologically
relevant conditions incubation of D3T with DTT caused remarkable oxygen consumption, indicating a redox reaction between D3T
and the dithiol molecule. Incubation of D3T with GSH also led to oxygen consumption, but to a less extent. Electron paramagnetic
resonance (EPR) studies showed that the redox reaction between D3T and DTT generated superoxide. Superoxide was also formed
from the redox reaction of D3T with GSH. These findings demonstrate that D3T reacts with thiols, particularly a dithiol, generating
superoxide, which may provide a mechanistic explanation for induction of Nrf2-dependent phase 2 enzymes by D3T. |
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Keywords: | EPR Superoxide D3T Oxygen consumption Thiols |
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