VESS 3 IL 3.1:
Vitamin E metabolism, inflammatory pathways and gut microbiota
Prof. Qing Jiang | Purdue University | United States
Natural forms of vitamin E, i.e., tocopherols and tocotrienols, are metabolized via -hydroxylase (CYP4F2)-initiated side chain oxidation to form 13’-hydroxychromanol and 13’-carobyxychromanol (13’-COOH), which are subsequently metabolized to terminal metabolite carboxyethyl-hydroxychroman (CEHC) and sulfated analogs. This presentation will focus on the impact of vitamin E metabolites including 13’-COOHs on inflammation in mechanistic, cellular and preclinical studies. In particular, 13’-COOHs have been shown to have anti-inflammatory effects, including inhibition of cyclooxygenase-1/-2 and 5-lipoxygenase activities. 13’-COOHs have also been documented to inhibit cancer cell growth, modulate cellular lipids and decrease nitric oxide synthase expression. Consistent with anti-inflammatory activities, TE-13’-COOH and αT-13’-COOH suppressed colitis-associated colon cancer and peritonitis, respectively, in mice. Potential interactions between TE-13’-COOH and gut microbes will also be discussed.
VESS 3 IL 3.2:
Emerging new understanding of the regulatory role of vitamin E in ferroptotic cell death.
Prof. Valerian E Kagan | Unive5rsity of Pittsburgh | United States
Valerian E. Kagan and Hülya Bayir, University of Pittsburgh, USA.
Hundred years of studies of vitamin E and members of this family leave no doubts that effective and safe scavenging of injurious radicals, particularly lipid peroxyl radicals represents its major biological function. Over the lase decade a new understanding of the regulatory mechanisms through which vitamin E exert its biological function has emerged. This relates to the ability of vitamin E to prevent/suppress a new type of regulated cell death, ferroptosis. There are two major mechanisms through which the anti-ferroptotic role of vitamin E is realized. 1. Vitamin E acts as a potent inhibitor of 15-lipoxygenase and its complexes with phosphatidylethanolamine (PE) binding protein 1 (PEBP1) and suppresses the production of the major pro-ferroptotic signal, 15-hydroperoxy-arachidonoyl-PE. 2. By interacting with coenzyme Q, vitamin E one-electron oxidation product, chromanoxyl radical, gets reduced back to its phenolic state and blocks the formation of the 15-hydroperoxy-arachidonoyl-PE signal. This is a part of the mechanism identified as ferroptosis suppressor protein 1 (FSP1). Supported by NIH U01AI156924, U01AI156923, AI145406, CA165065, CA243142, AI068021, GM113908, HL114453, AI156924, NS076511, AI156923, and NS061817.