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Published on: October 19, 2013
Ontogeny of proteolytic signaling and antioxidant capacity in fetal and neonatal diaphragm
1Centre for Neonatal Research and Education, The University of Western Australia, Crawley 6009, Western Australia, Australia.
Insights
The preterm diaphragm
Area of Science:
- Biochemistry
- Developmental Biology
- Physiology
Background:
- Upregulation of protein degradation pathways causes muscle weakness in adult diaphragms due to injury and inflammation.
- The preterm diaphragm's structural and functional immaturity increases susceptibility to injury and inflammation from antenatal and postnatal exposures.
- Understanding early-life diaphragm protein degradation is crucial for identifying pathological signaling in preterm infants.
Purpose of the Study:
- To characterize the ontogeny of diaphragm protein degradation pathways and antioxidant capacity during early life muscle maturation.
- To assess the relative roles of major proteolytic pathways and antioxidant capacity in ovine fetuses and lambs from 75 days to 200 days postconceptual age.
Main Methods:
- Gene expression and protein content analysis of calpain, caspase 3, and ubiquitin conjugating and ligase genes.
- Measurement of calpain II protein content and protease activity.
- Assessment of antioxidant gene expression over developmental time points.
Main Results:
- Calpain and caspase 3 expression increased during gestation (75-100/128 days) then decreased, while ubiquitin genes remained unchanged.
- Postnatal delivery rapidly upregulated most proteolytic genes, with calpain II protein and activity showing a similar trend.
- Antioxidant gene expression increased from 75 days gestation to 24 hours post-birth, then significantly decreased by 7 weeks postnatal age.
Conclusions:
- Proteolytic signaling and antioxidant capacity patterns in the developing diaphragm reflect adaptive processes to metabolic changes and muscle maturation.
- These findings provide insight into the developmental trajectory of diaphragm muscle integrity in early life.
- Further research can elucidate the specific mechanisms underlying these adaptive changes in preterm infants.
Abstract:
Although upregulation of protein degradation pathways contributes to the development of muscle weakness in response to muscle injury and inflammation in the adult diaphragm, less is known about the preterm diaphragm. Muscle development during the antenatal and early postnatal periods normally results in net growth. However, the structural and functional immaturity of the preterm diaphragm may predispose it to injury and inflammation induced by adverse antenatal and postnatal exposures. Characterization of the ontogeny of diaphragm protein degradation pathways in early life is essential to recognize altered signaling pathways under pathologic conditions in preterm babies. We assessed the relative role of the major proteolytic pathways and antioxidant capacity during muscle maturation in ovine fetuses and lambs from 75 days to 200 days postconceptual age. Gene expression and protein content of calpain and caspase 3 exhibited a similar profile with advancing gestation, increasing from 75 days to 100 days/128 days and subsequently decreasing gradually toward the end of gestation. In contrast, ubiquitin conjugating and ligase genes did not change during gestation. All proteolytic genes examined (except Ubiquitin) were upregulated rapidly after delivery, with a similar developmental trend observed in calpain II protein content as well as calpain protease activity. In contrast, antioxidant gene expression demonstrated a steady increase from 75 days gestation to 24 hr after birth, followed by a significant reduction at 7 weeks of postnatal age (P ≤ 0.002). The proteolytic signaling and antioxidant capacity patterns reflect the adaptive process to metabolic change and muscle maturity with development.
