α-Tocotrienol quinone modulates oxidative stress response and the biochemistry of aging

• Published in: Bioorganic & medicinal chemistry letters Vol. 21; no. 12; pp. 3693 - 3698
• Main Authors: Shrader, William D., Amagata, Akiko, Barnes, Adam, Enns, Gregory M., Hinman, Andrew, Jankowski, Orion, Kheifets, Viktoria, Komatsuzaki, Ryo, Lee, Edgar, Mollard, Paul, Murase, Katsuyuki, Sadun, Alfredo A., Thoolen, Martin, Wesson, Kieron, Miller, Guy
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ltd 15.06.2011; Elsevier
• Subjects: Aging; Aging - drug effects; Aging - physiology; alpha-tocotrienol; Animals; Antioxidants; Antioxidants - chemistry; Antioxidants - metabolism; Antioxidants - pharmacology; Benzoquinones - chemistry; Benzoquinones - pharmacology; Biological and medical sciences; blood-brain barrier; Cell metabolism, cell oxidation; Cell physiology; Cells, Cultured; Digital Biology; Dogs; Dose-Response Relationship, Drug; Fundamental and applied biological sciences. Psychology; General and cellular metabolism. Vitamins; Humans; Medical sciences; metabolites; Mice; Molecular and cellular biology; Molecular Structure; oxidative stress; Oxidative Stress - drug effects; Pharmacology. Drug treatments; Quinone; Rats; Redox; senescence; stress response; Tocotrienols; Vitamin E - analogs & derivatives; Vitamin E - chemistry; Vitamin E - pharmacology; Antioxidants; Redox; Aging; Digital Biology; Quinone; Oxidative stress; Intravenous administration; Metabolite; Blood brain barrier; Mitochondrial disorder; Dose activity relation; Vitamin E; Mechanism of action; Chemical synthesis; Dog; Hemisynthesis; Human; Fissipedia; Carnivora; Oxidation reduction; Ageing; Benzoquinone derivatives; Rodentia; Oral administration; Patient; Bioavailability; Antioxidant; Biological activity; Vertebrata; Mammalia; Animal; Pharmacokinetics
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2011.04.085

We report that α-tocotrienol quinone (ATQ3) is a metabolite of α-tocotrienol, and that ATQ3 is a potent cellular protectant against oxidative stress and aging. ATQ3 is orally bioavailable, crosses the blood–brain barrier, and has demonstrated clinical response in inherited mitochondrial disease in open label studies. ATQ3 activity is dependent upon reversible 2e-redox-cycling. ATQ3 may represent a broader class of unappreciated dietary-derived phytomolecular redox motifs that digitally encode biochemical data using redox state as a means to sense and transfer information essential for cellular function.