Erythropoietin-induced cytoprotection in intestinal epithelial cells is linked to system Xc<sup/>.
Necrotizing enterocolitis is a common but serious complication among premature babies. Currently, there are limited treatment options. These include intensive supportive care and surgical intervention. In this study, we hypothesize that erythropoietin (Epo) could be protective against cell necrosis by increasing the levels of glutathione. This can be regulated by increasing the activity of system xC-. This was demonstrated using intestinal epithelial cells (IEC-6) as a model system. S4-CPG and sulfasalazine pharmacologically inhibit xCT, which induced cell death. Our data showed a dose dependent decrease in cell viability when treated with both inhibitors. In addition, the IEC-6 cells displayed a dose dependent increase when treated with Epo. In conclusion, Epo can be protective against cell death and ultimately be considered as a treatment option for intestinal epithelial cell death.
Department of Surgery/Division of Pediatric Surgery and Center of Glial Biology in Medicine at the University of Alabama School of Medicine, Birmingham, AL 35294, USA.
Colin
C
Martin
Department of Pediatrics/Division of Neonatology and Center of Glial Biology in Medicine at the University of Alabama School of Medicine, Birmingham, AL 35294, USA.
Mikita
M
Patel
Department of Surgery/Division of Pediatric Surgery and Center of Glial Biology in Medicine at the University of Alabama School of Medicine, Birmingham, AL 35294, USA.
Miguel
M
Melendez-Ferro
Department of Pediatrics/Division of Neonatology and Center of Glial Biology in Medicine at the University of Alabama School of Medicine, Birmingham, AL 35294, USA. Electronic address: bsims@peds.uab.edu.
Brian
B
Sims
D027182:Amino Acid Transport System y+ / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D020345:Enterocolitis, Necrotizing / Q000378:metabolism* / Q000473:pathology; D004921:Erythropoietin / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D007223:Infant; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D012460:Sulfasalazine / Q000494:pharmacology
D027182:Amino Acid Transport System y+; C118895:SLC7A11 protein, human; D004921:Erythropoietin; D012460:Sulfasalazine; D005978:Glutathione
Erythropoietin; Hydrogen peroxide; Necrotizing enterocolitis; S4-CPG; Sulfasalazine; System xC(-)