TY - JOUR
T1 - Enteral arginine modulates inhibition of AP-1/c-Jun by SP600125 in the postischemic gut
AU - Ban, Kechen
AU - Santora, Rachel
AU - Kozar, Rosemary A.
N1 - Funding Information:
Acknowledgment This study was supported by grants from the National Institutes of Health (RO1GM077282).
PY - 2011/1
Y1 - 2011/1
N2 - We previously demonstrated that enteral arginine increased c-Jun/activator protein-1 (AP-1) DNA-binding activity and iNOS expression in a rodent model of mesenteric ischemia/reperfusion (I/R). The objective of this study was to specifically investigate the role of AP-1 in arginine's deleterious effect on the postischemic gut. We hypothesized that AP-1 inhibition would mitigate the effects of arginine. Using a rodent model of mesenteric I/R we demonstrated that gut neutrophil infiltration, activity of c-Jun/AP-1, as well as iNOS expression were increased by I/R and further increased by arginine while lessened by inhibition of c-Jun using the pharmacologic c-Jun N-terminal kinase inhibitor, SP600125. Similar results were demonstrated using a cell culture model of oxidant stress in IEC-6 cells. Importantly, effects of SP600125 were comparable to those of c-Jun silencing. Lastly, the specific iNOS inhibitor, 1400W, had no effect on either AP-1 or c-Jun. In conclusion, SP600125 attenuated the activity of c-Jun/AP-1, iNOS expression, and neutrophil infiltration induced by arginine following mesenteric I/R. Our data suggest that AP-1 inhibition mitigates the injurious inflammatory effects of arginine in the postischemic gut. Further investigation into the pathologic role of enteral argninine in the postischemic gut is warranted.
AB - We previously demonstrated that enteral arginine increased c-Jun/activator protein-1 (AP-1) DNA-binding activity and iNOS expression in a rodent model of mesenteric ischemia/reperfusion (I/R). The objective of this study was to specifically investigate the role of AP-1 in arginine's deleterious effect on the postischemic gut. We hypothesized that AP-1 inhibition would mitigate the effects of arginine. Using a rodent model of mesenteric I/R we demonstrated that gut neutrophil infiltration, activity of c-Jun/AP-1, as well as iNOS expression were increased by I/R and further increased by arginine while lessened by inhibition of c-Jun using the pharmacologic c-Jun N-terminal kinase inhibitor, SP600125. Similar results were demonstrated using a cell culture model of oxidant stress in IEC-6 cells. Importantly, effects of SP600125 were comparable to those of c-Jun silencing. Lastly, the specific iNOS inhibitor, 1400W, had no effect on either AP-1 or c-Jun. In conclusion, SP600125 attenuated the activity of c-Jun/AP-1, iNOS expression, and neutrophil infiltration induced by arginine following mesenteric I/R. Our data suggest that AP-1 inhibition mitigates the injurious inflammatory effects of arginine in the postischemic gut. Further investigation into the pathologic role of enteral argninine in the postischemic gut is warranted.
KW - Activator protein-1
KW - Arginine
KW - Inducible nitric oxide synthase
KW - Inflammation
KW - Mesenteric ischemia/reperfusion
KW - SP600125
UR - http://www.scopus.com/inward/record.url?scp=78651320398&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=78651320398&partnerID=8YFLogxK
U2 - 10.1007/s11010-010-0628-x
DO - 10.1007/s11010-010-0628-x
M3 - Article
C2 - 21046201
AN - SCOPUS:78651320398
SN - 0300-8177
VL - 347
SP - 191
EP - 199
JO - Molecular and Cellular Biochemistry
JF - Molecular and Cellular Biochemistry
IS - 1-2
ER -