INVESTIGATION ON THE MECHANISM OF VITAMIN A UPTAKE, ACCUMULATION AND METABOLISM IN THE LUNGS OF THE NEONATAL RAT
Open Access
- Author:
- Wu, Lili
- Graduate Program:
- Nutrition
- Degree:
- Master of Science
- Document Type:
- Master Thesis
- Date of Defense:
- September 04, 2008
- Committee Members:
- A Catharine Ross, Thesis Advisor/Co-Advisor
A Catharine Ross, Thesis Advisor/Co-Advisor - Keywords:
- retinoic acid
metabolism
vitamin A
neonatal lung
LRAT
CYP26B1 - Abstract:
- The lungs of humans, rodents and other mammals are immature at birth and undergo rapid development during the postnatal periods. Vitamin A (VA) is an essential nutrient that is required by the lung tissue in the postnatal period to help complete lung septation and maturation. Therefore, it is important to keep sufficient lung vitamin A in an early time of life. Previous studies have shown that retinol combined with its metabolite, retinoic acid (RA), is able to increase lung RE contents synergistically. A metabolic study has shown that RA redirects more of the VA given as a supplement into the neonatal lung. And this synergistic effect of combination of VA and RA (VARA) is only specific for the lung tissue. However, the mechanism of the synergy is unknown. To better understand vitamin A metabolism in the lungs, we investigated how RA and its synthetic, metabolism-resistant analog, Am580, affect the distribution and metabolism of newly absorbed retinol in the neonatal rat. We also studied the transcript level of some genes involved in vitamin A metabolism when neonatal rats were treated with RA or Am580. Our results had shown that treatment of RA and Am580 not only increased neonatal lung RE significantly but also drive more oral-taken retinol to the lung. At the gene level, both RA and Am580 can significantly up-regulate the expression of some retinoids metabolism genes, like lecithin: retinol acyltransferase (LRAT), a member of cytochromes P450 (CYP26B1) and stimulated by retinoic acid gene 6 (STRA6) in neonatal rat lung. Compared to a transient up-regulation with RA, Am580 shows prolonged effect in increasing the expression of LRAT and CYP26. In addition, a 6-h and a 12-h study showed that although both LRAT and CYP26B1 expression response to treatment of RA greatly, LRAT reaches to its peak level much earlier than CYP26. In conclusion, the administration of acidic retinoids redirects the flow of supplemented VA in the neonate body. Some important retinoids metabolism genes like LRAT, CYP26 and STRA6 may contribute to the redirection of VA flow and play a key role in VA metabolism in neonatal lung. From these data, a model is proposed that treatment of RA greatly up-regulates expression of LRAT in the neonatal rat lung (at about 6 hours). Although CYP26B1 expression is highly induced by RA too, the change is not as big as LRAT. The change in gene pattern results in more retinol uptake into lung tissue and more RE formation. Meanwhile, the increased expression of STRA6, which codes a membrane receptor for retinol binding protein (RBP), also contributes to VA uptake into the lung. Thus the synergistic effect of VARA in RE formation can be explained. Each year, more than 300,000 premature infants are born in the United States. This population is born with inadequate body stores of vitamin A and is prone to respiratory diseases. Considering the beneficial effects of VA in promoting lung development and maturation, it is desirable to develop an efficient and safe way to increase neonatal lung RE content in premature infants. Our study in VA metabolism in neonatal lung provides promising therapeutic option in clinical medicine.