Lipopolysaccharide-induced weakness in the preterm diaphragm is associated with mitochondrial electron transport chain dysfunction and oxidative stress

Yong Song, Gavin J Pinniger, Anthony J Bakker, Timothy James Murugesan Moss, P Noble, Clare A Berry, Jane Pillow

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Diaphragmatic contractility is reduced in preterm lambs after lipopolysaccharide (LPS) exposure in utero. The mechanism of impaired fetal diaphragm contractility after LPS exposure is unknown. We hypothesise that in utero exposure to LPS induces a deficiency of mitochondrial complex activity and oxidative damage in the fetal diaphragm. To test this hypothesis, we used a well-established preterm ovine model of chorioamnionitis: Pregnant ewes received intra-amniotic (IA) saline or 10 mg LPS, at 2 d or 7 d prior to surgical delivery at 121 d GA (term = 150 d). The fetus was killed humanely immediately after delivery for tissue sampling. Mitochondrial fractions were prepared from the isolated diaphragm and mitochondrial electron transfer chain activities were evaluated using enzymatic assays. Oxidative stress was investigated by quantifying mitochondrial oxidative protein levels and determining antioxidant gene and protein (catalase, superoxide dismutase 2 and glutathione peroxidase 1) expression. The activity of the erythroid 2-related factor 2 (Nrf2)-mediated antioxidant signalling pathway was examined by quantifying the Nrf2 protein content of cell lysate and nuclear extract. A 2 d LPS exposure in utero significantly decreased electron transfer chain complex II and IV activity (p
Original languageEnglish
Article numbere73457
Number of pages7
JournalPLoS ONE
Volume8
Issue number9
DOIs
Publication statusPublished - 2013

Cite this

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title = "Lipopolysaccharide-induced weakness in the preterm diaphragm is associated with mitochondrial electron transport chain dysfunction and oxidative stress",
abstract = "Diaphragmatic contractility is reduced in preterm lambs after lipopolysaccharide (LPS) exposure in utero. The mechanism of impaired fetal diaphragm contractility after LPS exposure is unknown. We hypothesise that in utero exposure to LPS induces a deficiency of mitochondrial complex activity and oxidative damage in the fetal diaphragm. To test this hypothesis, we used a well-established preterm ovine model of chorioamnionitis: Pregnant ewes received intra-amniotic (IA) saline or 10 mg LPS, at 2 d or 7 d prior to surgical delivery at 121 d GA (term = 150 d). The fetus was killed humanely immediately after delivery for tissue sampling. Mitochondrial fractions were prepared from the isolated diaphragm and mitochondrial electron transfer chain activities were evaluated using enzymatic assays. Oxidative stress was investigated by quantifying mitochondrial oxidative protein levels and determining antioxidant gene and protein (catalase, superoxide dismutase 2 and glutathione peroxidase 1) expression. The activity of the erythroid 2-related factor 2 (Nrf2)-mediated antioxidant signalling pathway was examined by quantifying the Nrf2 protein content of cell lysate and nuclear extract. A 2 d LPS exposure in utero significantly decreased electron transfer chain complex II and IV activity (p",
author = "Yong Song and Pinniger, {Gavin J} and Bakker, {Anthony J} and Moss, {Timothy James Murugesan} and P Noble and Berry, {Clare A} and Jane Pillow",
year = "2013",
doi = "10.1371/journal.pone.0073457",
language = "English",
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journal = "PLoS ONE",
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Lipopolysaccharide-induced weakness in the preterm diaphragm is associated with mitochondrial electron transport chain dysfunction and oxidative stress. / Song, Yong; Pinniger, Gavin J; Bakker, Anthony J; Moss, Timothy James Murugesan; Noble, P; Berry, Clare A; Pillow, Jane.

In: PLoS ONE, Vol. 8, No. 9, e73457, 2013.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Song, Yong

AU - Pinniger, Gavin J

AU - Bakker, Anthony J

AU - Moss, Timothy James Murugesan

AU - Noble, P

AU - Berry, Clare A

AU - Pillow, Jane

PY - 2013

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