Impaired fatty acid utilization in thioredoxin binding protein-2 (TBP-2)-deficient mice: a unique animal model of Reye syndrome
| Autor: | Shu Ichi Yamada, Shinichi Oka, Hajime Nakamura, Hiroshi Masutani, Junji Yodoi, Yoichi Shinkai, Hiromi Hirata, Wenrui Liu, Toru Yoshida |
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| Rok vydání: | 2005 |
| Předmět: |
medicine.medical_specialty
genetic processes Hemorrhage macromolecular substances Carbohydrate metabolism Biology environment and public health Biochemistry chemistry.chemical_compound Mice Thioredoxins Acetyl Coenzyme A Internal medicine Genetics medicine Animals Reye Syndrome Molecular Biology Blood Coagulation chemistry.chemical_classification Fatty Acids Fatty acid Metabolism Fasting Fatty Liver enzymes and coenzymes (carbohydrates) Oleic acid Disease Models Animal Endocrinology Glucose chemistry health occupations Ketone bodies Free fatty acid receptor Thioredoxin Carrier Proteins Food Deprivation Gene Deletion Biotechnology |
| Zdroj: | FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 20(1) |
| ISSN: | 1530-6860 |
| Popis: | Thioredoxin binding protein-2 (TBP-2) is a negative regulator of thioredoxin and has multiple regulatory functions in cellular redox, growth, differentiation, apoptosis, and aging. To investigate the function of TBP-2 in vivo, we generated mice with targeted inactivation of TBP-2 (TBP-2-/- mice). Here, we show that TBP-2 expression is markedly up-regulated during fasting in wild-type mice, while TBP-2-/- mice were predisposed to death with bleeding tendency, as well as hepatic and renal dysfunction as a result of 48 h of fasting. The fasting-induced death was rescued by supplementation of glucose but not by that of oleic acid, suggesting that inability of fatty acid utilization plays an important role in the anomaly of TBP-2-/- mice. In these mice, plasma free fatty acids levels are higher, whereas glucose levels are lower than those of wild-type mice. Compared with wild-type mice, TBP-2-/- mice showed increased levels of plasma ketone bodies, pyruvate and lactate, indicating that Krebs cycle-mediated fatty acid utilization is impaired. Because the fatal impairment of fatty acid utilization is a characteristically metabolic feature of Reye (-like) syndrome, TBP-2-/- mouse may represent a novel model for investigating the pathophysiology of these disorders. |
| Databáze: | OpenAIRE |
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