Abstract:
:Uteroplacental insufficiency alters the anabolic metabolism of the fetus, resulting in intrauterine growth retardation (IUGR). The metabolic and physiologic factors that cause IUGR have long standing consequences after birth. Postnatal growth and glucose metabolism are altered in the IUGR infant. Skeletal muscle is an important component of growth and metabolizes up to 70% of i.v. glucose. The ability of skeletal muscle to metabolize glucose is affected by ATP availability. We hypothesized that gene expression and function of proteins involved in mitochondrial ATP production and distribution would be altered in juvenile IUGR muscle. To test this hypothesis, we used a model of IUGR, induced by bilateral uterine artery ligation in the pregnant rat, that mimics uteroplacental insufficiency in the human. RT-PCR was used to measure the mRNA levels of three important mitochondrial proteins; NADH-ubiquinone-oxireductase subunit 4L(ND-4L), subunit C of the F1F0-ATP synthase (SUC), and adenine nucleotide translocator 1 (ANT1) in IUGR and control rats in fetal and juvenile life. In the fetus, mRNA levels of all three proteins were significantly increased in IUGR skeletal muscle. In contrast, in juvenile animals, mRNA levels of all three proteins were significantly decreased. mRNA levels of other metabolically important proteins, glucose-6-phosphate dehydrogenase and carnitine-palmitoyl-transferase II, were not significantly altered in IUGR juvenile animals. To assess if decreased gene expression is associated with altered mitochondrial function, we measured the mitochondrial NAD+/NADH ratio in d 21 juvenile control and IUGR muscle. At d 21, decreased gene expression if ND-4L, SUC, and ANTI is associated with a decreased mitochondrial NAD+/NADH ratio. The results of our study suggest that the metabolic alterations associated with uteroplacental insufficiency in the rat result in altered fetal and postnatal muscle mitochondrial mRNA expression as well as altered postnatal mitochondrial function.
journal_name
Pediatr Resjournal_title
Pediatric researchauthors
Lane RH,Chandorkar AK,Flozak AS,Simmons RAdoi
10.1203/00006450-199805000-00001subject
Has Abstractpub_date
1998-05-01 00:00:00pages
563-70issue
5eissn
0031-3998issn
1530-0447journal_volume
43pub_type
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journal_title:Pediatric research
pub_type: 杂志文章
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pub_type: 杂志文章,随机对照试验
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pub_type: 临床试验,杂志文章
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journal_title:Pediatric research
pub_type: 临床试验,杂志文章,随机对照试验
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pub_type: 临床试验,杂志文章
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pub_type: 杂志文章
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更新日期:2013-06-01 00:00:00
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doi:10.1203/PDR.0b013e318176182b
更新日期:2008-08-01 00:00:00
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pub_type: 杂志文章
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journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1203/00006450-199909000-00014
更新日期:1999-09-01 00:00:00
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journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1203/01.pdr.0000202757.47761.76
更新日期:2006-04-01 00:00:00
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pub_type: 杂志文章
doi:10.1038/s41390-018-0023-y
更新日期:2018-08-01 00:00:00
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pub_type: 杂志文章
doi:10.1038/s41390-020-0961-z
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