PT  - JOURNAL ARTICLE
AU  - Yong Song
AU  - Jane Pillow
TI  - Developmental profile of cellular pathways regulating protein breakdown in the fetal and postnatal diaphragm
DP  - 2011 Sep 01
TA  - European Respiratory Journal
PG  - p3801
VI  - 38
IP  - Suppl 55
4099  - http://erj.ersjournals.com/content/38/Suppl_55/p3801.short
4100  - http://erj.ersjournals.com/content/38/Suppl_55/p3801.full
SO  - Eur Respir J2011 Sep 01; 38
AB  - Studies on diaphragm weakness and atrophy focus on adult muscle, but the preterm diaphragm might be more susceptible to injury. Characterization of the ontogeny of protein degradation pathways responsible for muscle atrophy would help further understanding of the altered signaling pathways under pathologic conditions in preterm babies. Here, we performed the baseline study of major proteolytic pathways and antioxidant capacity in lambs from 75 d to 200 d postconceptual age. The diaphragm tissues were collected and analysed for gene expression and/or protein abundance in a set of key pathway components in conjunction with proteolysis/antioxidant activity. Our results showed that calpain and caspase 3 in gene and protein expressions exhibited a similar profile with advancing gestation, increasing from 75 d to 100 d/128 d and subsequently decreasing gradually toward full term. In contrast, ubiquitin conjugating and ligase genes did not change during gestation. All proteolytic genes examined (except Ubiquitin) were up-regulated rapidly after delivery, with a similar developmental trend observed in protease activities. Unlike proteolytic pathway pattern, antioxidant gene expression demonstrated a steady increase from 75 d gestation until 24 h after birth, followed by a significant reduction at 7 w of postnatal age (p ≤ 0.002). The proteolytic signaling and antioxidant capacity patterns reflected the adaptive process to metabolic change and muscle maturity with development. The data from this study may partly explain the susceptibility of preterm infants to respiratory failure in response to injurious ventilation and/or clinical stressors such as inflammation and hypoxia.