Dietary α tocopherol and neuromuscular health：Search for optimal dose and molecular mechanisms continues！英文电子书.pdf

Mol. Nutr. Food Res. 2010, 54, 693–709 DOI 10.1002/mnfr.200900575 693 REVIEW Dietary a-tocopherol and neuromuscular health: Search for optimal dose and molecular mechanisms continues! Kishorchandra Gohil, Vihas T. Vasu and Carroll E. Cross Department of Internal Medicine, Genome and Biomedical Sciences Facility, University of California, Davis, CA 95616, USA Rodents fed a-tocopherol (aT)-depleted diets develop neuromuscular deficits. Unequivocal role Received: November 27, 2009 of aT in the prevention of these deficits is confounded by possible neurotoxic oxidant products Revised: January 14, 2010 generated, ex vivo in aT-depleted diets. The discovery that large doses of aT could ameliorate Accepted: January 15, 2010 neuromuscular deficits, attributed to very low serum aT caused by mutations in either the microsomal triglyceride transfer protein or the aT-transfer protein (aTTP), underscores the necessity of aT for neuromuscular health in humans. The discovery of human aTTP provided physiological relevance to biochemical data from rodents documenting aT–binding transfer protein, expressed exclusively in liver. The cloning of aTTP gene and the creation of aTTP- knockout mice allowed to achieve severe systemic aT deficiency in brain and muscles, possibly at birth, eliminating the possible confounding effects of ex vivo-generated oxidant products in vitamin E-stripped diets. aTTP-knockout mice have proven useful models to discover aT-regulated phenotypes and molecular actions of aT in vivo. The results suggest that anti- oxidant and non-antioxidant actions of aT in vivo may not be mutually exclusive. These studies also suggest that low levels of dietary aT can achieve in excess of nanomolar aT levels in tissues and maintain normal neuromuscul