Lethal dysregulation of energy metabolism during embryonic vitamin E deficiency
| Autor: | Jaewoo Choi, Melissa McDougall, Gerd Bobe, Maret G. Traber, Robert L. Tanguay, Hye-Kyeong Kim, Enrique Cadenas, J. Frederik Stevens |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Docosahexaenoic Acids medicine.medical_treatment Pentose phosphate pathway Biology Mitochondrion Biochemistry Article Energy homeostasis 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Physiology (medical) Internal medicine medicine Animals Vitamin E Choline Vitamin E Deficiency Zebrafish Mitochondria 030104 developmental biology Endocrinology chemistry Docosahexaenoic acid Lipid Peroxidation Vitamin E deficiency Energy Metabolism Oxidation-Reduction 030217 neurology & neurosurgery Homeostasis |
| Zdroj: | Free Radical Biology and Medicine. 104:324-332 |
| ISSN: | 0891-5849 |
| DOI: | 10.1016/j.freeradbiomed.2017.01.020 |
| Popis: | Vitamin E (α-tocopherol, VitE) was discovered in 1922 for its role in preventing embryonic mortality. We investigated the underlying mechanisms causing lethality using targeted metabolomics analyses of zebrafish VitE-deficient embryos over five days of development, which coincided with their increased morbidity and mortality. VitE deficiency resulted in peroxidation of docosahexaenoic acid (DHA), depleting DHA-containing phospholipids, especially phosphatidylcholine, which also caused choline depletion. This increased lipid peroxidation also increased NADPH oxidation, which depleted glucose by shunting it to the pentose phosphate pathway. VitE deficiency was associated with mitochondrial dysfunction with concomitant impairment of energy homeostasis. The observed morbidity and mortality outcomes could be attenuated, but not fully reversed, by glucose injection into VitE-deficient embryos at developmental day one. Thus, embryonic VitE deficiency in vertebrates leads to a metabolic reprogramming that adversely affects methyl donor status and cellular energy homeostasis with lethal outcomes. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect