Deleterious effects of intestinal ischemia/reperfusion injury in the mouse enteric nervous system are associated with protein nitrosylation

Rivera, Leni Rose, Thacker, Michelle, Pontell, Louise, Cho, Hyun-Jung and Furness, John B. 2011, Deleterious effects of intestinal ischemia/reperfusion injury in the mouse enteric nervous system are associated with protein nitrosylation, Cell and tissue research, vol. 344, no. 1, pp. 111-123, doi: 10.1007/s00441-010-1126-x.

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Title Deleterious effects of intestinal ischemia/reperfusion injury in the mouse enteric nervous system are associated with protein nitrosylation
Author(s) Rivera, Leni Rose
Thacker, Michelle
Pontell, Louise
Cho, Hyun-Jung
Furness, John B.
Journal name Cell and tissue research
Volume number 344
Issue number 1
Start page 111
End page 123
Total pages 13
Publisher Springer
Place of publication Heidelberg, Germany
Publication date 2011-04
ISSN 0302-766X
Keyword(s) ischemia
nitric oxide synthase
enteric nervous system
Hu protein
Summary Changes 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 changesthat 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 anddistortion 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.
Language eng
DOI 10.1007/s00441-010-1126-x
Field of Research 110399 Clinical Sciences not elsewhere classified
1116 Medical Physiology
Socio Economic Objective 970111 Expanding Knowledge in the Medical and Health Sciences
HERDC Research category C1.1 Refereed article in a scholarly journal
ERA Research output type C Journal article
Copyright notice ©2011, Springer-Verlag
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Document type: Journal Article
Collections: Faculty of Health
School of Medicine
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