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Deleterious effects of intestinal ischemia/reperfusion injury in the mouse enteric nervous system are associated with protein nitrosylation
journal contribution
posted on 2011-04-01, 00:00 authored by Leni RiveraLeni Rivera, M Thacker, L Pontell, H-J Cho, J B FurnessChanges in intestinal function, notably impaired transit, following ischemia/reperfusion (I/R) injury are likely to derive, at least in part, from damage to the enteric nervous system. Currently, there is a lack of quantitative data and methods on which to base quantitation of changes
that occur in enteric neurons. In the present work, we have investigated quantifiable changes in response to ischemia of the mouse small intestine followed by reperfusion from 1 h to 7 days. I/R caused distortion of nitric oxide synthase (NOS)-containing neurons, the appearance of a TUNEL reaction in neurons, protein nitrosylation and translocation of Hu protein. Protein nitrosylation was detected after 1 h and was detectable in 10% of neurons by 6 h in the ischemic region, indicating that reactive peroxynitrites are rapidly produced and can interact with proteins soon after reperfusion. Apoptosis, revealed by TUNEL staining, was apparent at 6 h. The profile sizes of NOS neurons were increased by 60% at 2 days and neurons were still swollen at 7 days, both in the ischemic region and proximal to the ischemia. The distribution of the enteric neuron marker and oligonucleotide binding protein, Hu, was significantly changed in both regions. Hu protein translocation to the nucleus was apparent by 3 h and persisted for up to 7 days. Particulate Hu immunoreactivity was observed in the ganglia 3 h after I/R but was never observed in control. Our observations indicate that effects of I/R injury can be detected after 1 h and that neuronal changes persist to at least 7 days. Involvement of NO and reactive oxygen species in the changes is indicated by the accumulation of nitrosylated protein aggregates and the swelling and
distortion of nitrergic neurons. It is concluded that damage to the enteric nervous system, which is likely to contribute to functional deficits following ischemia and reoxygenation in the intestine, can be quantified by Hu protein translocation, protein nitrosylation, swelling of nitrergic neurons and apoptosis.
that occur in enteric neurons. In the present work, we have investigated quantifiable changes in response to ischemia of the mouse small intestine followed by reperfusion from 1 h to 7 days. I/R caused distortion of nitric oxide synthase (NOS)-containing neurons, the appearance of a TUNEL reaction in neurons, protein nitrosylation and translocation of Hu protein. Protein nitrosylation was detected after 1 h and was detectable in 10% of neurons by 6 h in the ischemic region, indicating that reactive peroxynitrites are rapidly produced and can interact with proteins soon after reperfusion. Apoptosis, revealed by TUNEL staining, was apparent at 6 h. The profile sizes of NOS neurons were increased by 60% at 2 days and neurons were still swollen at 7 days, both in the ischemic region and proximal to the ischemia. The distribution of the enteric neuron marker and oligonucleotide binding protein, Hu, was significantly changed in both regions. Hu protein translocation to the nucleus was apparent by 3 h and persisted for up to 7 days. Particulate Hu immunoreactivity was observed in the ganglia 3 h after I/R but was never observed in control. Our observations indicate that effects of I/R injury can be detected after 1 h and that neuronal changes persist to at least 7 days. Involvement of NO and reactive oxygen species in the changes is indicated by the accumulation of nitrosylated protein aggregates and the swelling and
distortion of nitrergic neurons. It is concluded that damage to the enteric nervous system, which is likely to contribute to functional deficits following ischemia and reoxygenation in the intestine, can be quantified by Hu protein translocation, protein nitrosylation, swelling of nitrergic neurons and apoptosis.
History
Journal
Cell and tissue researchVolume
344Issue
1Pagination
111 - 123Publisher
SpringerLocation
Heidelberg, GermanyPublisher DOI
ISSN
0302-766XeISSN
1432-0878Language
engPublication classification
C Journal article; C1.1 Refereed article in a scholarly journalCopyright notice
2011, Springer-VerlagUsage metrics
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