Autoantibodies against homocysteinylated protein in a mouse model of folate deficiency-induced neural tube defects
| Autor: | Katey Witham, Vinod Kumar, Richard H. Finnell, Kerina J. Denny, Trent M. Woodruff, Angela Jeanes, Christina F. Kelly, Stephen M. Taylor, Robert M. Cabrera |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Embryology medicine.medical_specialty Homocysteine 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Antigen Internal medicine Medicine chemistry.chemical_classification Pregnancy business.industry Autoantibody Neural tube Embryo General Medicine medicine.disease Amino acid 030104 developmental biology Endocrinology medicine.anatomical_structure chemistry Biochemistry Pediatrics Perinatology and Child Health Toxicity business 030217 neurology & neurosurgery Developmental Biology |
| Zdroj: | Birth Defects Research Part A: Clinical and Molecular Teratology. 106:201-207 |
| ISSN: | 1542-0752 |
| Popis: | Background Periconceptional supplementation with folic acid results in a significant reduction in the incidence of neural tube defects (NTDs). Nonetheless, NTDs remain a leading cause of perinatal morbidity and mortality worldwide, and the mechanism(s) by which folate exerts its protective effects are unknown. Homocysteine is an amino acid that accumulates under conditions of folate-deficiency, and is suggested as a risk factor for NTDs. One proposed mechanism of homocysteine toxicity is its accumulation into proteins in a process termed homocysteinylation. Methods & Results Herein, we used a folate-deficient diet in pregnant mice to demonstrate that there is: (i) a significant inverse correlation between maternal serum folate levels and serum homocysteine; (ii) a significant positive correlation between serum homocysteine levels and titers of autoantibodies against homocysteinylated protein; and (iii) a significant increase in congenital malformations and NTDs in mice deficient in serum folate. Furthermore, in mice administered the folate-deplete diet before conception, supplementation with folic acid during the gestational period completely rescued the embryos from congenital defects, and resulted in homocysteinylated protein titers at term that are comparable to that of mice administered a folate-replete diet throughout both the pre- and postconception period. These results demonstrate that a low-folate diet that induces NTDs also increases protein homocysteinylation and the subsequent generation of autoantibodies against homocysteinylated proteins. Conclusion These data support the hypotheses that homocysteinylation results in neo-self antigen formation under conditions of maternal folate deficiency, and that this process is reversible with folic acid supplementation. Birth Defects Research (Part A) 106:201–207, 2016. © 2016 Wiley Periodicals, Inc. |
| Databáze: | OpenAIRE |
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