Presented at the Neonatal Society 2002 Autumn Meeting.
Gnanalingham GM, Mostyn A, Wilson V, Symonds ME, Stephenson T
Academic Division of Child Health, School of Human Development, University Hospital, Nottingham NG7 2UH
Introduction: Mitochondria have a pivotal role in energy metabolism. Specific mitochondrial proteins regulate this process and their abundance is determined in part by cellular metabolic requirements. Voltage-dependent anion channel (VDAC) is located in the outer mitochondrial membrane and is involved in energy conversion and provision, as well as apoptosis and is highly abundant in lung alveoli. There is a large increase in VDAC abundance within the fetal lung between mid and late gestation (1) but the extent to which it may change further after birth following the onset of independent breathing has not been determined.
Methods: Lung samples (n = 4-7) were taken from fetuses at 140- and 147-days, from lambs at 4-6 hours, 7- and 30-days, and from adolescent lambs at 6-months, after humane euthanasia (100 mg/kg pentobarbital sodium: Euthatal). Delivery was by Caesarean section for fetuses and normal vaginal delivery for all other groups. Mitochondrial fractions were prepared and protein abundance was determined by immunoblotting, utilising a polyclonal antibody raised to ovine VDAC. Results (in arbitrary units) are presented as means with their standard errors (SEM). Differences between groups were analysed by one-way ANOVA with post-hoc Bonferroni.
Results: VDAC was more abundant in the fetal lung than immediately after birth (p=0.034), after which time levels increased to values similar to those observed in the fetus. By one month of postnatal age, however, VDAC levels were again lower than those in the fetal lung, and appeared to have plateaued by 6 months of age.
* p < 0.05 in VDAC abundance between 147-day fetus and 4-6 hour old lambs, 4-6 hours and 7-day old lambs, and 7-day and 6-month old adolescent lambs.
Conclusion: The higher levels of VDAC in the fetal lung are likely to be indicative of the increased energy turnover needed for solute exchange at this stage of fetal development. The transient decrease in VDAC after birth may then reflect the large changes occurring within the lung as independent breathing is established. The extent to which VDAC abundance further decreases with postnatal age as the lung continues to grow remains to be established.
References
1. Yakubu DP, Seetho IW, Mostyn A, Dandrea J, Wilson V, Symonds ME, Stephenson T. Proc Nutr Soc 2003 (In press).