The role of PKCdelta and PKCepsilon in the neonatal rat colon in response to hypoxia challenge.
Previous studies have determined that, in response to bacterial endotoxin, the colonic mucosa of the 10-d-old neonatal rat was more susceptible to injury than was the colon of the 25-d-old mature animal. Furthermore, it is known that certain isoforms of protein kinase C (PKC), specifically PKCdelta and PKCepsilon, mediate intestinal inflammatory responses to specific challenges. Therefore, in the present study, we have examined the association between the activation of these PKC isoforms and the enhanced susceptibility to hypoxia-induced challenge. In response to exposure to a hypoxic environment (14% O2/86% N2, 30 min), the degree of inflammation and tissue damage was significantly greater in 10- than in 25-d-old rats. The injury in 10-d-old rats was associated with activation of PKCdelta and PKCepsilon as estimated by translocation of the isoform from cytosolic to membrane fraction of the tissue lysate. There was no activation of either isoform in colons from 25-d-old rats after hypoxia. Pretreatment of 10-d-old rats with epidermal growth factor (EGF) (10 microg/kg) but not 16,16 dimethyl prostaglandin E2 (2 microg/kg) significantly reduced the extent of colonic injury, whereas neither agent was able to exert significant protection of the colonic mucosa of 25-d-old rats. PKC activation associated with hypoxia was not evident after EGF treatment in 10-d-old rats. In 25-d-old rats, prostaglandin E2 treatment was linked with an activation of PKCepsilon only. In conclusion, these data suggest that activation of PKCdelta and PKCepsilon is associated with the enhanced susceptibility to injury evident in suckling neonatal rat colon. EGF-mediated protection of the colon in these animals results in a removal of this PKC activation.
Conte
Melissa
M
Department of Physiology and Pharmacology, The University of Western Ontario, Medical Science Bldg., Room M226, London, Ontario, Canada N6A 5C1. btepperm@med.uwo.ca
Soper
Brian
B
Chang
Qing
Q
Tepperman
Barry
B
D000818:Animals; D000831:Animals, Newborn; D003092:Colitis / Q000378:metabolism; D003106:Colon / Q000201:enzymology*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D000860:Hypoxia / Q000378:metabolism*; D008297:Male; D009195:Peroxidase / Q000378:metabolism; D011493:Protein Kinase C / Q000235:genetics* / Q000378:metabolism*; D051745:Protein Kinase C-delta; D051744:Protein Kinase C-epsilon; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley
D012333:RNA, Messenger; D009195:Peroxidase; C497260:Prkcd protein, rat; C497257:Prkce protein, rat; D011493:Protein Kinase C; D051745:Protein Kinase C-delta; D051744:Protein Kinase C-epsilon