Inhibition of reactive oxygen species downregulates the MAPK pathway in rat spinal cord after limb ischemia reperfusion injury
Abstract Introduction We examined the activity of mitogen-activated protein kinase (MAPK) family members, extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38, in rats pinal cord after hind limb ischemia reperfusion (IR) and analyzed the role of reactive oxygen species...
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Published in | International journal of surgery (London, England) Vol. 22; pp. 74 - 78 |
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Main Authors | , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
England
Elsevier Ltd
01.10.2015
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Subjects | |
Online Access | Get full text |
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Summary: | Abstract Introduction We examined the activity of mitogen-activated protein kinase (MAPK) family members, extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38, in rats pinal cord after hind limb ischemia reperfusion (IR) and analyzed the role of reactive oxygen species (ROS) as mediators of MAPK signaling under these conditions. Methods In experiment 1, hind limb IR rats were treated intraperitoneally with one of following agents at 30 min before reperfusion: allopurinol (4, 40 mg/kg), superoxide dismutase (SOD, 4000 U/kg), N -nitro- l -arginine methyl ester ( l -NAME, 10 mg/kg), or SOD (4000 U/kg) + l -NAME (10 mg/kg). In experiment 2, 5,10,15,20-tetrakis ( N -methyl-4′-pyridyl) porphyrinato iron (III) (FeTMPyP) was administered intraperitoneally (1, 3, or 10 mg/kg) 30 min before reperfusion. After 3 d reperfusion period, the spinal cord (L4–6) was harvested to investigate MAPK signaling activity. Results In experiment 1, p-ERK and p-JNK levels were significantly higher in the IR group than sham group. Administration of allopurinol, SOD, l -NAME, or SOD + l -NAME significantly reduced the IR-induced increase in p-ERK and p-JNK levels. There were no significant differences in p-p38 levels. In experiment 2, FeTMPyP significantly reduced the IR-induced increase in p-ERK and p-JNK levels in a dose-dependent manner. Conclusions Activation of ERK and JNK in the spinal cord was induced by hind limb IR and was not accompanied by p38 activation. IR-induced MAPK phosphorylation was reduced by inhibition of superoxide, nitric oxide, and peroxynitrite, indicating that ROS produced by hind limb IR mediate the activation of these signaling pathways in the spinal cord, potentially affecting distant organs. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 1743-9191 1743-9159 |
DOI: | 10.1016/j.ijsu.2015.08.016 |